No. 3990 February 7, 2020

brosis. Chief commercial officer Stuart Arbuckle stated that 18,000 patients in the US are eligible for Trikafta, which has an annual list price of around $311,000, and “for 6,000 of these people, this is the first time they have had a medicine to treat the underlying cause.” He added that given the superiority of the profile, “we expect the vast majority of patients who are eligible for Trikafta are going to switch. Exactly how long that process will take, it’s hard to tell.” This will clearly lead to significant can- nibalization of Symdeko, Orkambi and Kalydeco in the US but Vertex is guiding for global full-year 2020 cystic fibrosis sales of $5.1-$5.3bn, up from $4.00bn in 2019. The older drugs are expected to make considerable contributions outside the US where Vertex has inked a number of reimbursement agreements in coun- Stunning Start For Vertex tries including France, Spain and Austra- lia. (Also see “Vertex Inks Another Orkambi Cystic Fibrosis Triple Combo Reimbursement Deal After France Says Yes” - Pink Sheet, 26 Nov, 2019.) (Also see “Ver- KEVIN GROGAN [email protected] tex Strikes Spanish Payment-For-Results CF Deal” - Pink Sheet, 22 Oct, 2019.) nalysts have been stunned by the The speed of the approval surprised in- The company finally agreed a market launch of Vertex Pharmaceuticals vestors, and Trikafta sales have seen even access deal with NHS England in October AInc.’s Trikafta, with the first triple more jaws drop. While the $420m figure last year following a protracted row over combination therapy for cystic fibrosis re- is inflated by $100m in inventory stock- Orkambi’s £100,000 per patient per year cording a whopping $420m in revenues ing, the sales represent one of the most list price that became one of the world’s just nine weeks since US approval. successful launches of any drug, and com- most high-profile drug price controver- Wall Street had been estimating sales in fortably exceed the first-quarter launches sies. The deal involved access to Orkambi, the region of $30m-$70m for Trikafta (el- combined of Vertex’s three older big-sell- Kalydeco and Symkevi, while Vertex also exacaftor/ivacaftor/tezacaftor) which was ing CF therapies – Symdeko (tezacaftor/ agreed to submit Trikafta to a “compre- approved by the US Food and Drug Ad- ivacaftor), Orkambi (lumacaftor/ivacaftor) hensive NICE appraisal.” (Also see “At Last: ministration on 21 October after a review and Kalydeco (ivacaftor). Vertex Strikes CF Deal In England” - Pink lasting just three months. The agency Trikafta is already Vertex’s top-selling Sheet, 24 Oct, 2019.) cleared the drug for patients 12 and older medicine followed by Symdeko, which Vertex expects to get European ap- who have at least one F508del muta- rose to $332m from $294m. Sales for Ork- proval for Trikafta for patients aged 12 tion in the cystic fibrosis transmembrane ambi fell to $270m from $315m, while and older in the fourth quarter of this year, conductance regulator (CFTR) gene five Kalydeco slipped to $236m from $259m. though many observers believe it could months ahead of the FDA’s March 2020 With the triple combo, Vertex can come sooner than that. A submission in action date. treat 90% of all patients with cystic fi- CONTINUED ON PAGE 4

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Coronavirus Challenge Brexit Is Here... Q4 Results Rush Companies join the fight against ....but biopharma uncertainty Pfizer, Roche, Novartis, Amgen, Biogen the new virus (p15-17) remains (p14) and Lilly reveal 2019 financials (p 4-13) IN THIS ISSUE

from the editor [email protected]

Novartis is clearly making a commercial success of sell- versial. With the number of doses limited by production ing the world’s most expensive drug. In the fourth quar- capacity, it is making them available to eligible infants ter it booked $186m in the US from treating just 100 via a bi-weekly draw. Novartis’s AveXis unit explains patients with Zolgensma, its FDA-approved gene thera- that it wants to avoid favouring one child or country py for spinal muscular atrophy (see p6). The treatment over another. However, the scheme does not take into is undeniably a huge breakthrough, offering the chance account patients’ access to Biogen’s Spinraza and is un- for what seems to be a once-and-done cure for a rare clear on important questions around information and disease that can be deadly within months of birth in the support for clinicians, and how data on its use will be most severe cases. The company was keen to emphasize captured. Patient organizations have questioned its eth- the positive take-up on insurance schemes, which it says ics and called on the company to let them help improve indicates broad acceptance of the treatment’s value de- the way it is administered. It is to be hoped that AveXis spite its £2.1m price tag. will work with these bodies. Pricing is a minefield but But in countries where Zolgensma has yet to be ap- free giveaways can be incendiary too; both need careful proved, Novartis’s program to offer free doses of the navigation. Setting up a lottery of life and death is prob- treatment to eligible infants with the disease is contro- ably a mis-step.

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2 | Scrip | February 7, 2020 © Informa UK Ltd 2020 4 Stockwatch: Biosimilars Pfizer On Biosimilars And Dividends

21 20 Lilly Product Pruning 11

exclusive online content inside: COVER / Stunning Start For Vertex Cystic Fibrosis Triple Combo

Amgen’s R&D Group Focuses On Efficiency 4 Pfizer’s Biosimilar Strategy Might Be Working As Drug Cost Concerns Continue 5 US Biosimilars Take A Bite Out Of Roche’s Herceptin MANDY JACKSON [email protected] 6 Zolgensma Stands Out In Strong Q4 For Novartis

7 Novartis CEO: Inclisiran Could Be Largest Medicine In NHS History

8 Otezla Is Amgen’s Main Growth Driver As Net Drug Pricing Declines

10 Biogen Is Putting Its Money Where Its Mouth Is – Behind The Launch Of

11 Lilly Calls It Quits On Pegilodecakin As Loxo Team Reorganizes Cancer R&D

13 Lilly, Allergan Beat Biohaven To Acute Migraine Market Amgen Inc. has been working for years to improve the effi- With Reyvow, Ubrelvy Launches ciency of its research and development group, but execu- tive vice president of R&D David Reese said that when he 14 Brexit Finally Here But Uncertainty Not Over For Biopharma moved into his role 18 months ago he looked at additional ways to streamline the organization so that it works within 15 Gilead Joins Coronavirus Fray With Repurposed Antiviral an industry business model that’s changing based on in- creasing concerns about the costs of new drugs. 16 Atriva Fast Tracks Antiviral Candidate As Coronavirus Arrives In Germany “What I really did was take a basic approach and say, ‘OK, what are our assumptions about the world over the next 17 JT Gains World-First Topical JAK Inhibitor Approval 10-15 years?’” Reese said in an interview during the recent J.P. Morgan Healthcare Conference in San Francisco. “The 18 Surprise! Pfizer And Lilly File For Pain With business model is changing, led by the US drug pricing dis- FDA Despite Safety Questions cussion, and clearly the industry is in a state of evolution, so any R&D organization has to be prepared to produce 19 Brilinta Boost For AZ In Stroke Study what we want to do, which is transformative medicines for 20 Atopic Dermatitis: Ruxolitinib And Baricitinib Spearheading that world to come.” New Therapies Amgen has decided to focus its efforts on three thera- peutic areas – cardiovascular disease, oncology and in- 21 Stockwatch: Biosimilars And Dividends Connect Earnings flammation – and will have important clinical trial read- At Pfizer And Roche outs across all three categories this year. Those three therapeutic areas represent a very large public health bur- 22 Pipeline Watch den with annual mortality across the globe equal to the 23 Appointments population of the state of California, Reese noted, which is 39.6 million. Published online 29 January 2020 @PharmaScrip /scripintelligence To read the rest of this story go to: https://bit.ly/37RNBWM

/scripintelligence /scripintelligence

scrip.pharmaintelligence.informa.com February 7, 2020 | Scrip | 3 HEADLINE NEWS/Q4 RESULTS

CONTINUED FROM PAGE 1 Exonics Therapeutics Inc., bringing Vertex parts to a great biopharma story: strong the US for children aged six-11 is planned into the area of Duchenne muscular dys- organic growth for the next few years for later this year. trophy. He added, “Our strategy is playing plus a growing and exciting pipeline Outgoing CEO Jeffrey Leiden, who will out exactly as we had planned and will of multiple drug candidates, significant be succeeded by chief medical officer position us for continued short-term and earnings and cash flow generation.” Reshma Kewalramani, noted that the long-term growth. The company has never JMP Securities also liked the pipeline company is making “excellent progress been stronger or better positioned for fu- but the broker said that “while some inves- advancing and broadening our pipeline ture success in cystic fibrosis and beyond.” tors are already looking down the road to beyond cystic fibrosis” and is now in the (Also see “Vertex Buys Semma, Gaining Cell what’s after cystic fibrosis, we remind that clinic with multiple new medicines in five Therapy-Based Type 1 Diabetes Treatments Trikafta has patent protection pending to other diseases. He highlighted Vertex’s “ - Scrip, 3 Sep, 2019.) (Also see “Deal Watch: 2037 and we believe the product is worth alpha-1 antitrypsin deficiency program, Vertex Expands Gene-Editing Efforts With A over $8bn, which provides ample time for including VX-814, which has recently en- Pair Of Deals” - Scrip, 10 Jun, 2019.) Vertex’s pipeline to bear fruit.” tered Phase II trials. Baird analyst Brian Skorney issued a Leiden also referenced data presented ANALYSTS SURPRISED AND note on 31 January saying the broker was in November by Vertex and partner CRIS- IMPRESSED downgrading the stock to neutral and PR Therapeutics AG from the first two pa- Chastened analysts, fresh from wildly “we’re moving to the sidelines.” He point- tients treated with CTX011, a one-time missing with their Trikafta forecasts, is- ed out that “Vertex is at all-time highs due CRISPR/Cas9 ex vivo gene-editing therapy. sued notes on 31 January full of praise for to absolute domination of their cystic The results showed sustained improve- Leiden’s stewardship. Investment bank fibrosis franchise, topped by blowout Tri- ments in hemoglobin in both transfusion- BMO said that European sales could ac- kafta sales and a steady build of investor dependent beta thalassemia and sickle celerate in 2020, with multiple countries enthusiasm for their pipeline.” cell disease, “which suggests that we may having completed reimbursement nego- He added: “We can’t fault those who be able to functionally cure these diseases.” tiations, arguing that faster adoption in want to remain bullish on the company’s As for business development, Leiden ex-US regions could lead to upward revi- prospects but our thesis has played out said that “we completed more transac- sions to guidance. and we aren’t going to stretch the valua- tions in 2019 than in the four prior years, Over at Jefferies, the analysts said that tion without more confidence in rapid and including the acquisitions of Semma Ther- Vertex, which is “humming on all cylin- successful pipeline progress.” apeutics Inc. and its cell therapy approach ders,” remains “the best growth story in for type 1 diabetes and gene editing firm large cap biotech. They have two critical Published online 31 January 2020 Pfizer’s Biosimilar Strategy Might Be Working JESSICA MERRILL [email protected]

fizer Inc.’s biosimilar business is well on its way to becom- ing a blockbuster business, even as the launch of three new Poncology biosimilars has just gotten underway. Pfizer an- nounced biosimilar revenues of $911m in 2019, with strong 19% growth driven by the US market – which had 70% growth itself. The substantial growth of Pfizer’s biosimilar business is notable, given that Pfizer only launched its first biosimilar in the US in late 2016, Inflectra (infliximab-dyyb), and that product got off to a noticeably lackluster start versus Johnson & Johnson’s branded Remicade (infliximab). The launch of Pfizer’s second and third US biosimilars in late 2018 – Retacrit (epoetin alfa-epbx), a biosimilar version of Amgen Inc.’s Epogen and Johnson & Johnson’s Procrit, and Nivestym (-aafi), a biosimilar of Amgen’s Neupogen – have built out the portfolio. (Also see “Pfizer’s Epogen Biosimilar Retacrit Launches At 33% Off In A US Market Where Amgen’s Al- ready Competitive” - Scrip, 14 Nov, 2018.) Retacrit has captured 20% of the market one year after launch- flecting 70% growth. In Europe, where Pfizer has had a biosimilar ing, the company reported during its 28 January fourth quarter business for longer, gained through the acquisition of Hospira Inc. earnings call, a different dynamic than Pfizer experienced with in 2015, revenues declined 6% to $395m. Pfizer said it expects to Inflectra, which struggled to gain share versus branded Remicade. see additional growth coming from biosimilars in 2020, driven by Pfizer reported US biosimilar revenues of $451m for the year, re- the launch of three new oncology biosimilars in the US.

4 | Scrip | February 7, 2020 © Informa UK Ltd 2020 Q4 RESULTS

The company launched Zirabev (-byzr) and Rux- ience (rituximab-pyyr), biosimilars of Roche’s Avastin and Rituxan, US Biosimilars Take A Bite in the US in December and is poised to launch Trazimera (trastu- zumab-gyyp), a biosimilar of Roche’s Herceptin, in February. All three biosimilars will launch at wholesale acquisition costs that Out Of Roche’s Herceptin are 22% to 24% lower than the branded drugs. ANDREW MCCONAGHIE [email protected] The company expects the uptake of biosimilar oncology medi- cines could be faster than in some chronic conditions because pa- fter defying the odds and keeping biosimilars at bay for tients cycle through treatment so quickly. much of 2019, Roche’s resistance faltered in the final quar- Ater, as it saw US sales of its breast cancer blockbuster Her- “We see the dynamics in oncology ceptin sink by 24%. This was a deeper erosion than expected, but nevertheless biosimilars being very differ­ent.” – Roche reassured investors with its Q4 and full year results,with group sales rising by 9% to CHF61.4bn ($63.2bn) driven up by a Angela Hwang cadre of new products. Posting the most impressive growth was Roche’s immuno- oncology blockbuster Tecentriq (atezolizumab), which saw its full year sales reach CHF1.85bn ($1.93bn), a rise of 143%. This was “We see the dynamics in oncology biosimilars being very differ- helped in particular thanks to its lead in small-cell lung cancer and ent from that of what we saw for inflammation in the form of In- triple-negative breast cancer. flectra,” Biopharmaceuticals group president Angela Hwang said Also rising sharply were hemophilia therapy Hemlibra (emici- during the company’s same-day conference call. zumab) and multiple sclerosis drug Ocrevus (ocrelizumab), both She pointed out that Pfizer’s launch of three new cancer bio- exceeding expectations with revenues rising to $1.42bn and similars all around the same time could be an advantage as well, $3.8bn respectively for the full year. as the company looks to build relationships with providers. Among the company’s newer breast cancer treatments re- Beyond the oncology biosimilars, Pfizer has secured FDA approval placing Herceptin’s lost revenues, Kadcyla ( emtan- of a biosimilar version of AbbVie Inc.’s Humira (adalimumab) called sine) was in-line with expectations but Perjeta () was Abrilada (adalimumab-afzb), which it expects to launch in 2023. weaker. This franchise also faces competition in the shape of As- traZeneca PLC and Daiichi Sankyo Co. Ltd.’s newly approved En- STRONG BIOPHARMA GROWTH hertu (fam--nxki). The biosimilar franchise was just one piece of Pfizer’s pharma- In terms of earnings per share, the company was able to out- ceutical portfolio that generated strong growth in 2019 as the perform analyst forecasts by 1% thanks to resolving a tax dispute. company heads into a big transition year when it will spin out its Overall, the company was able to ride out the impact of bio- Upjohn branded generics and established products business into similars on its big three earners – Herceptin (trastuzumab), Avastin a new company with Mylan NV called Viatris GMBH. (Also see “At (bevacizumab) and Rituxan/MabThera (rituximab) as expected, Pfizer, A Split A Decade In The Making” - Scrip, 29 Jul, 2019.) giving the company breathing space as it prepares to expand in- Sales of the breast cancer drug Ibrance grew 20% to $4.96bn in dications for its new portfolio and plans for further new launches 2019. Ibrance, in the US, has maintained a 90% share of the mar- over the next few years. ket, despite the availability of two competing CDK4/6 competi- Roche’s CEO Severin Schwan said he was pleased with the com- tors. In another crowded field, the blood thinner Eliquis partnered pany’s efforts at “rejuvenating” its portfolio, and forecast sales with Bristol-Myers Squibb Co., grew 23% to $4.22bn, and sales of growth in the low-to mid-single digit range, in spite of biosimilars the oral rheumatoid arthritis drug Xeljanz grew 26% to $2.24bn. being expected to take an even bigger bite out its big three brands. Despite strong growth across key brands, the impact of Lyrica The company launched new cancer drugs Polivy and Rozlytrek generic competition could not be avoided. Total revenues de- in 2019, and added indications for Tecentriq and Kadcyla. clined 4% on a reported basis to $51.75bn as expected. One of its key milestones for 2020 is for the regulatory review However, the biopharma business that Pfizer plans to move and anticipated launch of risdiplam, its new contender in the spi- forward with after the spinout grew 5% to $39.42bn. The growth nal muscular atrophy (SMA). The company will be taking on Bio- came from volume, not price, which had a negative 2% impact gen Inc.’s established Spinraza (nusinersen) and Novartis AG’s Zol- on biopharma results. Revenues for the Upjohn business, where gensma (onasemnogene abeparvovec), which yesterday posted Lyrica now falls, fell 18% to $10.23bn. strong growth from its first nine months on the market. The company laid out its 2020 forecast for the new Pfizer includ- Another key challenge will be the integration of gene therapy ing revenues of $40.7bn to $42.3bn, adjusted diluted earnings per specialists Spark Therapeutics, which is among a number of compa- share of $2.25 to $2.35 and operating cash flow of $11bn to $12bn. nies developing gene Roche Partnering Casts Wide Separately, Pfizer also confirmed that it filed the NGF inhibitor therapies for hemo- Net To Expand Company’s tanezumab with the US Food and Drug Administration for pain in philia A. Neuroscience Pipeline: moderate-to-severe osteoarthritis patients. Published online https://bit.ly/2RTvAle Published online 31 January 2020 31 January 2020

scrip.pharmaintelligence.informa.com February 7, 2020 | Scrip | 5 Q4 RESULTS

Zolgensma Stands Out In Strong Q4 For Novartis

KEVIN GROGAN [email protected]

ith Novartis AG’s quarterly fi- ing therapy and soon to be seen with the nancials revealing no great oral therapy, do you want your child on Wsurprises, the focus was on the a chronic therapy for decades or do you impressive launch of gene therapy Zol- want a one-time therapy?” gensma and the Swiss major’s confidence He added that “this is going to be our that it will see off competition from other core positioning. Down the line with players in the spinal muscular atrophy “This also gives us combination therapies, we’ll have to see (SMA) field. confidence that we can how the data plays out but we’re not con- Zolgensma (onasemnogene abeparv- cerned about that because we still believe ovec) was launched in the US in June last provide a compelling in the end, if you’re a parent of a child, you year to much fanfare and with a $2.1m ultimately would prefer a single 30-min- price tag. Novartis noted that full-year value proposition from ute infusion, then have to have the con- sales were $361m, with $186m coming in this one-time therapy.” – cern of a lifetime of chronic therapy.” the fourth quarter when 100 new patients were treated. Vas Narasimhan NEW DRUGS DELIVER CEO Vas Narasimhan said the launch Zolgensma was not the only new drug continued to progress well, telling re- from the bumper crop launched by No- porters that reimbursement policies are vartis in 2019 that performed well in the in place covering 97% of commercial pa- fourth quarter. Piqray (alpelisib), the first tients and over 50% of Medicaid patients. Narasimhan said that the 15 children drug to be approved for treatment of HR+, Currently, 16 states representing 32% of from the first Zolgensma trial “now grow HER2-negative breast cancer with PIK3CA newborns are screening for SMA in the US. beyond the age of five years and we keep mutations, contributed $67m, while the This means “only one patient who is on seeing no loss of their overall improve- wet age-related macular degeneration label for Zolgensma didn’t get fully reim- ments [so] questions about durability, I therapy Beovu () brought in bursed by the US health insurance system,” expect, will start to become less of a topic. $35m following its launch in October. he said, “which shows that the medicine This is a medicine that creates extraordi- Sales of Mayzent (siponimod), ap- provides tremendous value, that’s how pay- nary clinical results and offers incredible proved in March in the US as the first oral ers look at it. This also gives us confidence as value to the healthcare system.” treatment specifically indicated for active we roll the medicine out around the world He went on to point out that the gene secondary progressive MS and given the that we can provide a compelling value therapy was deemed cost effective by the green light in Europe this month, were proposition from this one-time therapy.” Institute for Clinical and Economic Review, lacklustre, coming in at $17m. Novartis Narasimhan confirmed that Novartis ex- adding that Zolgensma “costs less than said that “efforts are ongoing to acceler- pected to receive a positive opinion in the half what the competitor treatment costs ate patient on-boarding and drive urgen- first quarter from the European Medicines over 10 years.” cy to treat.” Agency’s drug evaluation committee, the The CEO was referring to Biogen Inc.’s Most impressive were the sales of CHMP, and approval in Japan in the first SMA blockbuster Spinraza (nusinersen), heart failure therapy Entresto (valsartan/ half of 2020. A number of filings have been approved by the FDA in 2016 and admin- sacubitril), which shot up 65% to $518m, submitted elsewhere “and it’s important to istered three times annually as an injec- and Cosentyx (secukinumab) for pso- note that SMA is an important burden of tion into the patient’s spinal cord. Another riasis, psoriatic arthritis and ankylosing disease in the Middle East, Latin America potential treatment is close to hitting the spondylitis. The latter, Novartis’s biggest- and other regions around the world.” market with Roche’s risdiplam, a daily seller, had sales of $965m, up 21%, and He also addressed the clinical hold that orally administered liquid, having an ac- head of pharma Marie-France Tschudin the US Food and Drug Administration tion date at the FDA of 24 May this year. noted that Cosentyx is “relatively un- placed on an intrathecal formulation of Speaking about the competition, Nara- touched by new competitors coming in Zolgensma which is being tested in type 2 simhan said, “We continue to believe we the marketplace” and is outperforming SMA patients in the STRONG trial. The firm have a better profile simply because we the market both in dermatology and is working with the agency to provide an- are a one-time therapy. If you look at the rheumatology indications. swers to questions concerning preclinical alternatives, if you have a child who is Overall, Novartis’s fourth quarter sales data which showed a safety issue related severely ill from SMA or has significant were $12.4bn, up 9% on the like, year- to dorsal root ganglia mononuclear cell disability… if you have the opportunity earlier period. Core operating income rose inflammation and hopes to file the intra- with a one-time therapy to achieve higher 13% to $3.46bn. thecal program by the end of 2020. responses potentially versus the exist- Published online 29 January 2020

6 | Scrip | February 7, 2020 © Informa UK Ltd 2020 Q4 RESULTS

Novartis CEO: Inclisiran Could Be Largest Medicine In NHS History KEVIN GROGAN [email protected]

aving recently inked a world-first Speaking about the collaboration as The third part of the deal includes the deal with NHS England for its in- Novartis unveiled its full-year financials creation of an industry and academic Hvestigational new cholesterol on 29 January, head of pharma Marie- consortium to look at manufacturing treatment inclisiran, acquired through France Tschudin noted that the NHS synergies that could improve the ef- the $9.7bn purchase of The Medicines partnership was made up of three mem- ficiency and scale at which the UK can Co., Novartis AG’s senior management oranda of understanding. The first is a make oligonucleotide medicines such as has been musing on how similar popula- population health agreement, upon reg- inclisiran. Tschudin noted that “they’re in tion-based agreements could transform ulatory approval and National Institute preliminary phases and we’re obviously the way big pharma and healthcare sys- for Health and Care Excellence (NICE) in conversations with the UK government tems do business. assessment, to provide inclisiran for sec- around all three. What is really interesting The pact, announced at the J.P. Morgan ondary prevention to atherosclerotic is this novel approach [is] an opportunity healthcare conference in San Francisco, cardiovascular (CV) disease patients, for us to work with healthcare systems in a centers around inclisiran, a first-in-class while the second involves a large-scale very different way.” small-interfering RNA (siRNA) drug that in- primary prevention clinical trial evalu- She added, “We know low-density li- hibits synthesis of PCSK9 which has been ating the use of the drug to patients at poproteins (LDL) or ‘bad’ cholesterol is a filed in the US and Europe that NHS Eng- very high risk of having their first cardiac huge issue because of the lack of adher- land said could offer “a cutting-edge new event. That trial “is something that we ence, and we feel that inclisiran twice a cholesterol treatment that has the poten- would be working on not only with the year injected at a physician’s office can re- tial to save up to 30,000 lives over the next UK, but hopefully with other countries,” ally have the potential to increase adher- 10 years.” she said. TURN TO PAGE 8

Scrip Awards Winner 2019 Business Development Team of the Year

This team successfully negotiated the P&G acquisition of Merck Consumer Health providing P&G with all the capabilities it lost with the dissolution of the PGT Healthcare Partnership between P&G and Teva. It also gained a fast-growing portfolio of brands that off ered Winner: Procter & Gamble’s Business P&G accelerated OTC growth, a stronger geographic Development Team footprint and a more balanced portfolio. The PGT agreement also enabled the transfer of several Teva OTC regulatory experts to P&G.

It was a great honor for our team to receive the Business Development Team of the Year Award in recognition of P&G’s eff orts in simultaneously negotiating the dissolution of our joint venture with Teva and the acquisition of the Merck Consumer Health business. Many thanks to the judges for recognizing the signifi cance and challenges associated with these accomplishments, particularly amongst so many strong fi nalists in this Award category. Tom Finn, President, P&G Personal Health Care

JN3095 Scrip Awards 2019 Winner Advert C.indd 1 2020/01/31 06:46 scrip.pharmaintelligence.informa.com February 7, 2020 | Scrip | 7 Q4 RESULTS

CONTINUED FROM PAGE 7 ence and make a dent in CV disease and CV mortality over time.” Otezla Is Amgen’s Main (Also see “Novartis Pharma President Marie-France Tschudin On Inclisiran, Launches And More “ - Scrip, 28 Jan, 2020.) Novartis is looking to position inclisiran as an attractive treat- Growth Driver As Net Drug ment alternative to the under-performing PCSK9 inhibitors al- ready on the market, Sanofi/Regeneron Pharmaceuticals Inc.’s Pricing Declines Praluent () and Amgen Inc.’s Repatha (). MANDY JACKSON [email protected] Those drugs are monoclonal antibodies that must be adminis- tered every two or four weeks – whereas inclisiran is dosed twice mgen Inc.’s near-term growth will come almost entirely a year – and despite their prices being slashed, Praluent and from its newly acquired Otezla (apremilast), consider- Repatha have failed to live up to early expectations since their Aing the company’s revenue guidance for 2020 is $25bn- launch in 2015. $25.6bn versus its 2019 revenue of $23.4bn; the difference is CEO Vas Narasimhan also enthused about the potential of the equal to the likely sales total this year for Otezla. NHS tie-up. He noted that “there’s about 1.8 million patients in the However, executives noted during Amgen’s fourth quarter and UK who would be eligible from a secondary prevention stand- full year 2019 sales and earnings call on 30 January that some of point from launch.” the company’s other products – Enbrel (etanercept) and certain He added that as data become more available, especially from biosimilars – could benefit from being positioned alongside Ote- the outcomes study in 2024, “there is a potential to further expand zla, which is approved for psoriasis and psoriatic arthritis. that. There would be a clear commercial potential right from the Still, while Amgen’s 2020 revenue guidance was in line with start with inclisiran been broadly used in the UK.” analyst consensus, it didn’t inspire a lot of confidence in newer Naarasimhan said that he “can’t guide obviously to specific branded products, since it appears that most growth in 2020 will numbers, but we think it’s highly attractive with respect to that come from Otezla and the company’s biosimilars business – that launch.” He noted that Tschudin and her team “are very actively portfolio is expected to reach $1bn in sales this year based on the discussing now with payers in the US as well as other parties fourth quarter 2019 total of $258m. around the world to see if can we use similar population-based Despite those two positive line items, however, the rest of Am- agreements to drive significant volume uptake, even ahead of the gen’s commercial portfolio is suffering from ongoing competi- outcomes study.” tion from biosimilars and generics of prior blockbusters as well as The CEO said, “It’s certainly our aspiration that we would want to global drug pricing pressure. make it one of the largest medicines, or if not, the largest medicine “With regard to net selling prices, we experienced a 5% decline in the history of the NHS. But we have many steps to get there. We globally in 2019,” chief financial officer Peter Griffith said during have to get the medicine approved, we have to arrive at the final the company’s earnings call. “For 2020, we expect to again experi- agreement with the UK and NICE and then ultimately we need to ence low- to middle-single-digit declines globally. We expect our drive significant uptake within the NHS system.” (Also see “Is NICE’s volume growth to more than offset the net price declines.” Pricing Influence On The Wane?” - Pink Sheet, 28 Jan, 2020.) Sales volume increases for brands still protected by patents did Narasimhan added, “What we’re excited about is the commit- not help total product sales in 2019, however, due to significant ment of the NHS to work together with us to drive that uptake.” He declines for off-patent brands, including the long-acting neutro- claimed it was “truly unprecedented for the head of the NHS and penia treatment Neulasta (), which dropped 28% myself to sit together and discuss the introduction of a medicine last year to $3.22bn, and the secondary hyperparathyroidism into the NHS system and the goal of driving large-scale utilization drug Sensipar/Mimpara (cinacalcet), which fell 69% to $551m. together, including the NHS directly working on driving that utili- Amgen reported total product sales of $5.88bn in the fourth quar- zation themselves. ter of 2019, which was down 2% from $6bn for the same period in “I think this shows the potential of this medicine to impact what 2018. Full year sales dipped 1% to $22.2bn from $22.53bn in 2018. is the leading cause of death and disability for healthcare systems. Amgen reported $178m in partial fourth quarter sales of Otezla I have been genuinely impressed by the partnership that we’ve after completing its $13.4bn acquisition of the drug from Celgene seen with the NHS and relevant UK government agencies on this.” Corp. and Bristol-Myers Squibb Co. in November – a deal that fa- He concluded by saying that the primary prevention trial, “tak- cilitated US Federal Trade Commission approval of Bristol’s $74bn ing a vaccine-like approach that could even prevent the first heart purchase of Celgene. Otezla sales totaled $1.6bn in 2018 and Cel- attack from happening, will start later this year. Working through gene expected 2019 sales to total $1.9bn; Amgen has said it ex- the NHS, we could dramatically reduce the cost of this clinical trial,” pects low single-digit growth from the product with potential for Narasimhan claimed. further growth from new indications. Tschudin said that the integration of The Medicines Company, Otezla occupies a unique psoriasis market niche where it is the deal for which closed on 6 January, was going well and should prescribed after topical therapies and before biologics, which be completed by March. After that, “the key focus for this year is Amgen plans to use to its advantage not just in marketing the to provide broad and affordable access and start engaging with phosphodiesterase 4 (PDE4) inhibitor, but also to boost sales of payers in multiple different countries.” its blockbuster TNF inhibitor Enbrel and its anti-TNF biosimilars, Published online 31 January 2020 whose indications include psoriasis. The company sells the Hu-

8 | Scrip | February 7, 2020 © Informa UK Ltd 2020 Q4 RESULTS

mira (adalimumab) biosimilar Amgevita in Amgen’s 2019 Branded Drug Sales Europe and will launch its newly approved Many key brands grew, but multiple legacy brands had big double-digit declines as they Remicade (infliximab) biosimilar Avsola in faced new or ongoing biosimilar or generic competitors. the US later this year. 2019 SALES 2018 SALES CHANGE Enbrel, Amgen’s top-selling product, achieved $5.23bn in 2019 sales, up 4% Prolia () $2.67bn $2.29bn 17% from $5.01bn in 2018, but executive vice Evenity () $189m NA NA* president of global commercial operations Repatha (evolocumab) $661m $550m 20% Murdo Gordon noted during the compa- Aimovig () $306m $119m NA* ny’s earnings call that “sales increased 2% year-over-year driven by a $6m favorable Parsabiv (etelcalcetide) $630m $336m 88% change in accounting estimates and in- Otezla (apremilast) $178m NA NA* creases in net selling price, partially offset Enbrel (etanercept) $5.23bn $5.01bn 4% by unit volume declines. Volume trends in Kyprolis (carfilzomib) $1.04bn $968m 8% 2020 are expected to be similar to those Xgeva (denosumab) $1.94bn $1.79bn 8% in 2019. As for net selling price, we project limited benefit in 2020 versus 2019 due to Vectibix () $744m $691m 8% less favorable contract terms.” Nplate (romiplostim) $795m $717m 11% Noting the prospect of marketing En- Blincyto (blinatumomab) $312m $230m 36% brel alongside Otezla, Gordon said, “with Neulasta (pegfilgrastim) $3.22bn $4.48bn -28% two highly complementary products tar- Neupogen (filgrastim) $264m $365m -28% geting psoriasis and psoriatic arthritis, we see an opportunity to strengthen their po- Epogen (epoetin alfa) $867m $1.01bn -14% sitions in the market.” Aranesp (darbepoetin alfa) $1.73bn $1.88bn -8% The psoriasis opportunity with Otezla is Sensipar/Mimpara $551m $1.77m -69% set to expand if Phase III studies in mild- (cinacalcet) to-moderate psoriasis that will read out in Total Product Sales** $22.2bn $22.53bn -1% mid-2020 are positive and Amgen wants *Aimovig launched in mid-2018, so full-year sales aren’t comparable; Evenity was approved in to take advantage of the drug’s position in 2019; and Otezla was acquired in November 2019. **Sales of smaller products, biosimilars not the marketplace. included in this table. Source: Amgen Inc. Executive vice president of research and development David Reese said dur- NET PRICES WILL DROP IN Q1 Biologics for migraine prevention that ing Amgen’s earning call that “in mild-to- Amgen is under a lot of pressure to return inhibit the calcitonin gene-related peptide moderate psoriasis there currently are no to sales growth beyond its acquired drug (CGRP) – Aimivog, marketed in partnership approved oral therapies. The only thing Otezla, given the erosion of sales for Neu- with Novartis AG, Eli Lilly & Co.’s Emgality really available to patients right now is lasta, Sensipar and other high-performing () and Teva Pharmaceutical topical therapy. Many of them will not ul- products. Among Amgen’s newer prod- Industries Ltd.’s Ajovy () – timately experience disease control with ucts, 2019 sales of the cholesterol-lower- have battled for market share by providing those topical therapies, and so we think ing therapy Repatha (evolocumab) rose a lot of free initial doses of their products. there is a real opportunity for Otezla in 20% to $661m. The migraine prophylaxis However, Gordon said more than 80% of that area. There are nearly 6 million pa- Aimovig (erenumab), which launched in Aimovig sales are now paid prescriptions. tients with mild-to-moderate psoriasis in the US in mid-2018 and generated $119m Repatha, on the other hand, is mak- the United States alone, so that gives you that year, brought in $306m in 2019. The ing headway with its lower-priced prod- a sense of the size of this opportunity and full year Aimovig total included $98m uct continuing to achieve uptake among actually the prevalence of the disease.” in the fourth quarter, which was just 3% commercially insured patients and with CEO Robert Bradway noted during the more than the $95m in Q4 2018, but last more Medicare Part D patients able to ac- call that “we also expect that Amgevita, year’s October-to-December period ben- cess the PCSK9 inhibitor at an affordable our biosimilar to Humira in Europe and efitted from $20m worth of positive ac- co-pay, Gordon said. Amgen introduced other parts of the world, will benefit from counting adjustments. a lower list price version of the biologic our recent acquisition of Otezla.” Gordon didn’t set the stage for a robust in October 2018 and stopped selling the Gordon also stated that the company’s increase in Aimovig sales in 2020, how- original version of the product at the end Amgevita sales efforts in Europe “syner- ever, since he noted that Amgen had to of 2019, in an effort to lower out-of-pocket gize nicely with Otezla.” take a significant price cut to obtain reim- costs for Medicare patients. Amgevita sales totaled $215m in its first bursement from CVS Caremark this year. “Q4 sales grew by 26% year-over-year full year on the market versus $11m in That means that net Aimovig pricing will as we continue to be the leader in the 2018. Amgen said its product is the top- decline in the first quarter, but he said it PCSK9 class,” Gordon said. selling Humira copy in Europe. should stabilize thereafter. Published online 30 January 2020

scrip.pharmaintelligence.informa.com February 7, 2020 | Scrip | 9 Q4 RESULTS

Biogen Is Putting Its Money Where Its Mouth Is – Behind The Launch Of Aducanumab JESSICA MERRILL [email protected]

iogen Inc. is increasing its spending substantially in 2020 the two Phase III trials, ENGAGE and EMERGE, including a sta- to build out commercial infrastructure to support the tistically positive benefit in cognitive decline in patients treat- Blaunch of aducanumab for Alzheimer’s disease in the US, ed with the highest dose of aducanumab after a clinical trial even though approval by the US Food and Drug Administration protocol change that allowed patients with the ApoE4 gene to is far from guaranteed. be titrated up to the highest dose. (Also see “Biogen’s Big Day “We are actively preparing for the potential launch of adu- Arrives, But Aducanumab Results Don’t Answer Key Question” - canumab with an initial focus on the US,” CEO Michel Vounatsos Scrip, 5 Dec, 2019.) told investors during the company’s 30 January earnings confer- Biogen has said it has a green light from the FDA to file the ence call. “This includes implementing a thorough go-to-market data, but some investors are still skeptical that it will result in model, hiring the sales force, building out our medical teams and an approval. However, the commercial opportunity could be preparing for market access.” big and aducanumab is the only prospective near-term launch The company announced fourth quarter and 2019 financials for the company. and issued 2020 forecasts, which includes a significant uptick in However, Biogen also has not yet finalized the submission or selling, general and administrative (SG&A) spending. SG&A spend- given guidance on when it will. Executive vice president of R&D ing is expected to be 19.5% to 20.5% of total revenues, a potential Al Sandrock indicated during the call that the only things holding increase of approximately $350m to $550m in 2020 versus 2019. up the filing are technicalities and documentation that must be Biogen spent $2.38bn on S&GA in 2019, which was about 16.5% of completed before finalizing the submission. He said Biogen has revenues. The new forecast suggests Biogen could spend $2.73bn also begun engaging with regulatory authorities outside of the to $2.93bn on SG&A in 2019, based on flat to slightly declining US about potential filings. revenue forecasts. Management said the increase would go toward commercial A CHALLENGING FINANCIAL YEAR and R&D expenses related to aducanumab. Biogen’s 2020 forecast calls for revenues of $14bn to $14.3bn, “We’re not going to give specific perspective on numbers in flat or slightly below 2019 revenues of $14.38bn, as a key terms of the launch, but I would just point you back to looking growth-driver, Spinraza (nusinersen), faces competition from at the SG&A guidance, which is up quite a bit from a percentage Novartis AG’ gene therapy Zolgensma and a potential new en- perspective, and you get a sense of the amount we’re spending trant from Roche. year-over-year,” chief financial officer Jeffrey Capello said during Spinraza sales grew 22% in 2019 to $2.1bn, but growth stopped the conference call. “That is, I think, the prudent thing to do given in the fourth quarter, when sales of Spinraza fell 1% year-over- the significant opportunity ahead of us.” year to $543m. The company attributed the slower sales to the Investing heavily to support the launch could be risky. Adu- timing of shipments, loading-dose dynamics and price, but not canumab isn’t an asset that is guaranteed to get to the market this competitive dynamics. year, given the conflicting clinical trial data Biogen hopes will sup- Biogen’s other key franchise, Tecfidera (dimethyl fumarate) for port FDA approval. multiple sclerosis, is maturing and could face generic competi- Nonetheless, management said it is moving forward with com- tion, but the company said its 2020 revenue guidance does not mercial hires, initially focusing on medical affairs and biomanufac- include the impact of a generic this year. A decision in an ongoing turing, to focus on engagement with scientific leaders and to pre- inter partes review (IPR) challenge by the US Patent and Trade- pare manufacturing to meet commercial demand. The company mark Office’s Patent Trial and Appeal Board (PTAB) is expected in said it is also engaging with pharmaco-economic experts around February, which Biogen said it will appeal if the outcome is not in the potential pricing for aducanumab. its favor. Tecfidera intellectual property challenges also are pend- “We engage broadly, and we ask for advice and we listen,” Vou- ing in various lawsuits. natsos said. Sales of Tecfidera increased 4% for the year to $4.43bn in 2019. Biogen gave investors whiplash last year when it said it The company is hoping to switch patients to a new fumarate would submit aducanumab to FDA after it had previously dis- product, Vumerity (diroximel fumarate), which launched late last continued two Phase III trials testing the drug following an year and offers a potential improvement in gastrointestinal toler- interim futility analysis. The company said the decision came ability. (Also see “Biogen Vumerity Receives Full US Approval, But GI after a more detailed analysis of the data revealed that one Comparison With Tecfidera Must Wait “ - Pink Sheet, 31 Oct, 2019.) of the studies had a positive outcome and the other was less The drug reached market in the fourth quarter and generated just negative than it seemed. (Also see “An About Face As Biogen $5m through the end of December. Says It Will File Aducanumab In Alzheimer’s “ - Scrip, 22 Oct, 2019.) In December, Biogen presented a complex dataset for Published online 31 January 2020

10 | Scrip | February 7, 2020 © Informa UK Ltd 2020 Q4 RESULTS

Lilly Calls It Quits On Pegilodecakin As Loxo Team Reorganizes Cancer R&D JOSEPH HAAS [email protected]

li Lilly & Co. is going through a reorganization driver behind Lilly’s $1.6bn buyout of Armo BioSci- of its cancer research and development ences Inc. in May 2018. (Also see “$1.6bn ARMO Eoperations, and early changes since Buy Gives Lilly Its Most Advanced Immuno- the pharma turned this responsibility Oncology Asset” - Scrip, 10 May, 2018.) over to the executive team from Loxo Chief scientific officer Daniel Oncology Inc. in December have Skovronsky said pegilodecakin begun, notably including a deci- combined with checkpoint in- sion to pull the plug on further hibitors failed to meet the pri- development of pegilodecakin mary endpoint in the CYPRESS after trial failures in pancreatic 1 and CYPRESS 2 studies. The and lung cancer. former investigated the com- Lilly reported during its fourth bination of pegilodecakin and quarter and full-year 2019 sales Merck & Co. Inc.’s Keytruda and earnings call on 30 January Lilly said it has no (pembrolizumab) versus Key- that pegilodecakin, a pegylated, plans for further trials truda monotherapy in first-line of pegilodecakin and recombinant human -10 NSCLC patients with high expres- terminated three therapy, failed in a pair of Phase II stud- earlier-stage cancer sion of PD-L1 (greater than 50%). ies in non-small cell lung cancer (NSCLC). candidates The latter study tested a combination Pegilodecakin, which also failed in a Phase III of the IL-10 candidate with Bristol-Myers study in pancreatic cancer last October, was the Squibb Co.’s Opdivo (nivolumab) versus Opdi-

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vo monotherapy in second-line NSCLC patients who were low or non-express- “Although we’re still analyzing­ the totality of the data ers of PD-L1. The primary endpoint in both studies that we have obtained with pegilodecakin, at present was objective response rate 36 months after the last patient was randomized; we do not anticipate additional trials with this agent.” each study also had overall survival and – Daniel Skovronsky progression-free survival as second- ary endpoints. In the Phase III SEQUOIA study, pegilodecakin combined with the FOLFOX (folinic acid, 5-fluorouracil and oxaliplatin) chemotherapy regimen failed advanced RET fusion-positive NSCLC, RET- list price increases and higher rebates as to demonstrate an overall survival benefit mutant medullary thyroid cancer and RET well as reduced reliance on patient as- compared to FOLFOX alone in second- fusion-positive thyroid cancer. The NDA sistance programs primarily due to im- line, metastatic pancreatic cancer. (Also has been granted a priority review and proved commercial access for Emgality.” see “Lilly’s Pegilodecakin Fails Pancreatic a decision is expected in July or August. For the year, pricing yielded a 3% drag Cancer Test” - Scrip, 17 Oct, 2019.) (Also see “Lilly’s Loxo Bet Pays Off In Thyroid on US sales revenue, Smiley added. “Although the full data will be pre- Cancer, A Second Indication For Selperca- Trulicity was the company’s top seller, sented at a medical meeting later this tinib” - Scrip, 30 Sep, 2019.) bringing in $4.13bn for the year (up 29% year, I can say that both [NSCLC] stud- over 2018) and $1.21bn during the quar- ies were negative,” Skovronsky told the MEDICARE DRAG ON US SALES ter (up 31%). Jardiance fell shy of block- call. “Though we are disappointed in DROPPED TO 1% IN Q4 buster sales for the year at $944m, but the lack of efficacy for pegilodecakin Overall, Lilly reported fourth quarter sales grew 43% year-over-year, with quarterly in combination with checkpoint inhibi- growth of 8% and full year growth of 4%. sales up 39% to $268m. Four of Lilly’s tion in lung cancer, we remain commit- In the fourth quarter, increasing sales seven blockbusters in 2019 came from ted to finding new therapies for people were driven by 10% volume growth, but its diabetes franchise – besides Trulicity, with cancer. Although we’re still analyz- as expected the pricing impact of Lilly’s these included Humalog/ Lispro ing the totality of the data that we have exposure to Medicare and Medicaid less- ($2.82bn, down 6%), Humulin ($1.29bn, obtained with pegilodecakin, at present ened in the quarter compared to the third down 3%) and Basaglar ($1.11bn, up we do not anticipate additional trials quarter. (Also see “Did Lilly Overcome US 39%). (Also see “Lilly Says Volume Growth with this agent.” Price Pressures In Last Quarter? Investors Strategy, Launches Working Despite Price Biomedtracker shows that pegilodeca- Await Answer” - Scrip, 28 Jan, 2020.) Pressures” - Scrip, 30 Apr, 2019.) kin was also being studied in Phase I liver, In October, the pharma noted during Taltz tallied full year sales of $1.37bn, up breast, ovarian and colorectal cancers, as its third quarter earnings report that US 46%, including fourth quarter revenues well as melanoma. In a slide presentation, prescription volume for two of its growth of $420m, up 37%. Breast cancer drug Lilly also revealed that it has terminated leaders – Trulicity (dulaglutide) for diabe- Verzenio exceeded 100% growth with full three earlier-stage cancer candidates – a tes and Taltz (ixekizumab) for psoriasis – year sales of $580m (up from $255m in Phase II TGF beta RI kinase inhibitor as well had risen much more sharply than sales 2018) and quarterly sales of $179m (com- as an IDO1 inhibitor and a TIM-3 antibody revenue, due partly to price drag from pared to $83m a year before). candidate, both in Phase I. Medicare Part D. (Also see “Lilly’s Diabetes In its first full year on the market as a Skovronsky pointed out three early- Franchise Poised For A Shakeup As Conter- migraine-prevention treatment, Emgal- stage cancer candidates that Lilly sees as no Steps Down” - Scrip, 23 Oct, 2019.) ity posted annual sales of $163m and very promising – a KRAS G12C inhibitor, US sales revenue increased 7% year- fourth quarter sales of $66m, after bring- a CD226 agonist and a selective estrogen over-year during the fourth quarter, with ing in nearly $5m at the end of 2018. Lil- receptor degrader (SERD), all in Phase I. Trulicity, Taltz, Verzenio (abemaciclib), ly will soon pair Emgality with Reyvow He said Lilly’s cancer R&D primarily will Jardiance (empagliflozin) and Emgal- (lasmiditan), approved by the FDA in focus on “high-probability” biology. “We ity (galcanezumab) leading 8% volume October to treat acute migraine, offer- will also from time to time continue to growth, chief financial officer Joshua ing patients a suite of migraine therapy pursue more novel biology, higher-risk, Smiley said. options. Launch has been waiting on high-reward bets like pegilodecakin was,” “Pricing was a 1% drag on US rev- scheduling by the US Drug Enforce- the exec added. “And that will be a smaller enue growth this quarter, impacted by ment Administration, which execs told part of our portfolio in the future.” increased funding during the coverage the earnings call is expected 31 January, Meanwhile, Lilly expects RET inhibitor gap in Medicare, unfavorable changes in with the product hitting the market the to be one of its three drug estimates for rebates and discounts and following week. (Also see “Lilly Expands launches in 2020, Skovronsky said, as a disproportionate volume growth in lower Migraine Franchise With Reyvow Approv- new drug application is under review at net-price segments,” he explained, “which al” - Scrip, 11 Oct, 2019.) the US Food and Drug Administration for was partially offset by the net of modest Published online 31 January 2020

12 | Scrip | February 7, 2020 © Informa UK Ltd 2020 LAUNCHES

Lilly, Allergan Beat Biohaven To Acute Migraine Market With Reyvow, Ubrelvy Launches MANDY JACKSON [email protected]

t was a neck-and-neck race to the mar- ket for new acute migraine treatments, IReyvow (lasmiditan) from Eli Lilly & Co. and Ubrelvy (ubrogepant) from Al- lergan PLC, but both oral drugs are now available for prescription in the US. The US Food and Drug Administration approved Lilly’s Reyvow, a 5-HT 1F recep- tor agonist, in October and the company announced on 31 January that the final roadblock to the product’s launch has been removed now that the Drug Enforce- ment Administration (DEA) has scheduled the drug as a Class V controlled substance, indicating a low risk of abuse or depen- dence. Reyvow will be available in phar- macies within the next few days and Lilly set a list price of $640 for eight tablets. Not to be outdone, Allergan informed Scrip on 31 January that Ubrelvy, a cal- About three quarters Reyvow, Ubrelvy and rimegepant will citonin gene-related peptide (CGRP) in- compete against generic triptans and hibitor, is in pharmacies and prescriptions of migraine sufferers over-the-counter non-steroidal anti- are being filled. The company, which is in inflammatory drugs (NSAIDs) to treat the process of being acquired by AbbVie are women the millions of patients who experience Inc. for $66bn, got US FDA approval for migraine headaches and other symp- Ubrelvy in December. (Also see “Allergan’s toms – an estimated 30 million-plus in Oral CGRP Inhibitor Ubrelvy Approved For the US alone. Migraine Attacks” - Scrip, 24 Dec, 2019.) ing a regular pill and a fast-dissolving Zydus It’s a market that requires multiple Reyvow is Lilly’s second new migraine tablet, and plans to launch its drug imme- treatment options because the symp- drug to reach the market in less than two diately following the agency’s endorse- toms vary, “so you really can’t have a one years. Reyvow was approved a year after ment. Biohaven also wants to add migraine size fits all approach to treating migraine the October 2018 approval of Emgality prevention to the drug’s label and plans to – you need different treatment options,” (galcanezumab) for the prevention of epi- report Phase III results for rimegepant in Libby Driscoll, vice president of Lilly’s US sodic and chronic migraine. (Also see “Lilly that indication during the first quarter. neuroscience business unit, explained in Expands Migraine Franchise With Reyvow an interview. Approval” - Scrip, 11 Oct, 2019.) Emgal- HOW PRICING COMPARES: “We know that because when we ask ity also is indicated for the prevention UBRELVY VS. REYVOW patients, ‘Are you willing to try something of episodic cluster headaches. (Also see Allergan set the bar for acute migraine new?’ 79% of patients say ‘Yes, if there’s “Keeping Track: First RMAT Approval On drug pricing in the US with a list price something new available I’d be willing The Horizon; Big Weeks For Merck, Lilly And of $85 per dose, which the Institute of to try it.’ I think that speaks to the unmet Celgene” - Pink Sheet, 7 Jun, 2019.) Clinical and Economic Review (ICER) need,” Driscoll said. Allergan already markets Botox (ona- determined to be cost effective. (Also Lilly is optimistic that Reyvow will botulinumtoxinA) for the prevention of see “The ICER Process: Allergan Engage- have broad reimbursement in the US, chronic migraine and it has a second oral ment Improves Cost Effectiveness Rating where more than 90% of people cov- CGRP inhibitor, atogepant, in Phase III For Ubrelvy “ - Scrip, 27 Jan, 2020.) Lilly’s ered by commercial health insurance studies for migraine prevention. $640 list price for eight Reyvow tablets plans have access to Lilly’s preventive Meanwhile, Biohaven Pharmaceutical works out to $80 per pill, essentially in CGRP inhibitor Emgality. Holding Co. Ltd. expects a US FDA approval line with Ubrelvy’s cost; it remains to be The company sees potential for com- decision in the first quarter of this year for seen where Biohaven’s rimegepant pric- bination therapy with Reyvow to treat its oral CGRP inhibitor rimegepant, includ- ing will land. breakthrough migraine attacks that occur

scrip.pharmaintelligence.informa.com February 7, 2020 | Scrip | 13 LAUNCHES/BREXIT

despite a patient’s use of a CGRP inhibitor good for everyone.” Headache special- to drive and their ability to assess whether or other preventive therapy, Eric Pearl- ists told Scrip that they look forward to they are able to drive, he said. man, senior medical director of neurosci- being able to prescribe Reyvow as an Reyvow required DEA scheduling be- ence at Lilly, told Scrip. acute migraine treatment, especially for cause of its low risk of abuse. Lilly con- “We do recognize that NSAIDs and patients who cannot take triptans be- ducted a study of the drug’s abuse and de- triptans are effective medicines and are cause those drugs cause vasoconstric- pendence potential and recreational drug recommended by professional societies tion. However, the doctors noted that users reported less likability for Reyvow as effective acute treatments, and we’re they would be careful about Reyvow than for the benzodiazepine alprazolam, not suggesting that they don’t have a prescribing given the sedation and diz- but more likability than placebo. However, place,” Pearlman said. “But we also know ziness associated with the drug. there was no risk of dependence. that even with those treatments avail- Lilly’s Pearlman noted that sedation Published online 31 January 2020 able, there is still an incredible unmet along with dizziness and paresthesia need, so the ability to provide an inno- were the most common side effects ob- The ICER Process: Allergan vative, unique mechanism of action for served with Reyvow in clinical trials. The Engagement Improves Cost acute treatment as another tool in that drug comes with a warning that patients Effectiveness Rating For Ubrelvy: toolkit for patients and health care pro- should not drive for eight hours after tak- https://bit.ly/2GOxzAO viders to better manage the disease is ing Reyvow, because it affects their ability Brexit Finally Here But Uncertainty Not Over For Biopharma

ANDREW MCCONAGHIE [email protected]

fter three and a half years of conflict and confusion over Warren says it is the BIA’s position that the UK government Brexit, the UK formally leaves the European Union at 23.00 has promised this, and that the BIA will continue to push for AGMT tonight, but the big questions about its future rela- a deal which provides certain alignment with EU rules – in- tions with Europe and the rest of the world have yet to be tackled. cluding the European Medicines Agency (EMA) –– but which The so-called transition period begins on 1 February and runs could also allow the UK to diverge in other areas of pharma- until 31 December 2020, in which time the UK hopes to secure a ceutical regulation. free trade agreement (FTA) with the EU. However, the legal com- plexities, the breadth of business sectors to be covered and the NEGOTIATING POSITIONS tricky trade-offs to be negotiated means it could be impossible to However, this will undoubtedly sound like “having your cake and agree a comprehensive deal in this timescale. eating it” – and while alignment on areas such as pharmacovigi- For the biopharma sector, the most crucial questions center lance would not be contentious, the EU has made it clear that the on how closely aligned the UK will remain with EU27 nations – or UK cannot hold on to all the privileges of EU membership when it whether the UK will set itself up as an economic competitor rather leaves the single market and customs union. than a collaborator. The UK and EU are expected to publish their respective negoti- Prime Minister Boris Johnson has made it clear that he wants ating mandates in the next few weeks, after which talks can begin Britain to maximize the potential of Brexit and has suggested it in March. could diverge from the EU towards a low-tax, lean-regulation ap- Tim Sarson is a partner at KPMG and its Brexit tax & location proach – sometimes dubbed as ‘Singapore-on-Thames’, to mimic lead. He has been working closely with the life sciences sector the dynamic economy of the Asian city state. over the last three and half years and says big pharma compa- However, this is something that both the UK pharma indus- nies are generally well prepared for any eventuality – includ- try organisation the ABPI and its biotech counterpart the BIA ing the possibility of a failure to agree an FTA by the end of the have argued against. They still hope to achieve EU alignment, transition period in December, which would effectively result in despite mixed signals from government, including Chancellor a “hard Brexit”. Sajid Javid. Nevertheless, he thinks a deal on alignment can be done. “One Presenting the latest webinar update to the associations’ thing that definitely doesn’t seem to be on the table is a sector- biopharma members, the BIA’s Brexit lead Michael Warren specific deal – the EU have been very clear on this. However, in reiterated:“We say it is absolutely in the UK’s interests to align on pharma I suspect that the end result will be that the UK stays in medicines for the safety of patients, access to medicines and the pretty close alignment in most areas, particularly pharmacovigi- interests of our world leading life science industry. That does leave lance, good manufacturing/distribution practice and pharma the door open potentially to a side-deal on prioritizing life scienc- compliance as well as the use and sharing of personal data ie, es as a protocol to a broader free trade agreement.” GDPR,” he says.

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“It’s possible there may be some divergence in terms of specific access to innovative medicines and/or clinical trials where the Gilead Joins government sees a benefit for the NHS.” Making matters even more complicated for the UK negotiators is the stated desire of the prime minister and US officials for a rap- Coronavirus Fray With id US-UK trade deal agreement as well. “Leaving aside the ‘NHS for sale’ stories, there are certainly some Repurposed Antiviral demands from US pharma that are contrary to EU regulatory BRIAN YANG [email protected] norms, specifically things like extended patent protection. We’ll see,” added Sarson. One of the areas requiring most urgent clarification for the sec- tor is how trade and regulation between Northern Ireland and the rest of the UK will work – as the province will take on a special status in order to avoid a hard border in Ireland. This will see it remain the UK customs area, but at the same time have to align with EU single market rules. This in turn will require some checks on goods moving between Great Britain and North- ern Ireland. The BIA’s CEO Steve Bates told Scrip recently that a great many practical questions about this arrangement need to be decided urgently – such as whether medicines might have to be re-labelled if moving across the Irish Sea.

WILL COMPANIES RELOCATE OR INVEST ELSEWHERE? The UK sector’s big fear is that Brexit will make it significantly less attractive. Since the 2016 referendum, it has been unclear companies have generally paused investment decisions – but s the Wuhan coronavirus continues to spread both inside that could change. China and around the world, a number of pharma firms The long-term risk remains, says Sarson. “Until Brexit, if you were Aand vaccine developers are rushing to respond. establishing a European HQ, the UK was always on the location Gilead Sciences Inc. has become the latest company to enter shortlist, even if it didn’t win. Now it is no longer guaranteed even the fray, saying it is now working with both US and China regula- to make the shortlist.” tors to get its experimental antiviral agent remdesivir to affected UK life science leaders, such as Sir John Bell and the Office of Life patients. There is currently no available effective antiviral drug for Sciences have been working hard to counteract these downsides the new 2019-nCoV virus. with new incentives and closer working with biopharma to tackle In a 31 January statement, the US antiviral specialist said it’s other bottlenecks and barriers. Read the full article here working with Chinese health authorities to establish a random- Finally, one of the biggest areas of concern for UK businesses ized, controlled trial to determine the safety and efficacy of its -nu are migration rules. This is a vital question for UK life sciences, cleotide analog prodrug, not yet approved anywhere for any use. which does not want to be handicapped in attracting the best EU This was originally intended for the Ebola and Marburg viruses, and global talent. although it failed to show efficacy against Ebola. “We are also expediting appropriate laboratory testing of rem- GLOBAL TALENT VISAS desivir against 2019-nCoV samples,” noted Gilead. The ABPI says there are 6,000 businesses in the UK life sciences The company cited structural similarities between 2019-nCoV sector competing for highly skilled scientists, and that research and previous viral pathogens MERS (Middle East Respiratory predicts there will be more than 31,000 more jobs that need to Syndrome) and SARS (Severe Acute Respiratory Syndrome), also be filled by 2025. caused by coronaviruses. “Remdesivir has demonstrated in vitro The UK government recently unveiled its plans for a ‘Global Tal- and in vivo activity in animal models” against both these, said Gil- ent’ visa, something which the sector has welcomed but will need ead, and the drug has been used compassionately in the first US further reassurance on. case of the virus. Even if the post-Brexit migration rules remain liberal, the So far, the only antiviral officially recommended by China’s -Na country will have a job to do to put that message out to the tional Health Commission to treat the new Wuhan coronavirus rest of the world. is AbbVie Inc.’s combination for HIV, Kaletra (lopinavir and ritona- “One big worry remains the ability to attract senior scientific vir), twice daily together with nebulized alpha-interferon. staff to the UK and uncertainty over the UK’s involvement in pan- Gilead added that it is also working with China’s main drug European research and trials in the future,” concludes Sarson. “This regulator, the National Medical Products Administration (NMPA), is based on perception as much as actual regulations, so there is along with the US FDA, Centers for Disease Control and other reg- not much government can do to influence decisions like these.” ulatory agencies to contribute antiviral expertise and resources to Published online 3 February 2020 help fight the new outbreak.

scrip.pharmaintelligence.informa.com February 7, 2020 | Scrip | 15 CORONAVIRUS OUTBREAK

DIAGNOSTICS, TCMS are no supporting clinical studies showing turing, as well as direct interactions with A paper authored by Chinese researchers, its efficacy in this regard. Chinese authorities, while GeoVax will based on 425 confirmed cases collected use its MVA-VLP platform and expertise from Wuhan, shows that the transmission CORPORATE VACCINE to design and construct a vaccine candi- rate (Ro) of the new virus is 2.2, similar to ALLIANCES date using genetic sequences from the that of SARS. Other new vaccine development col- ongoing coronavirus outbreak. So far, the NMPA has fast-tracked the laborations are also emerging in response The new alliance follows that be- approval of seven testing kits for the new to the crisis, including between Wuhan- tween Johnson & Johnson and Inovio virus, and the agency said it is getting in- based BravoVax and US vaccine developer Pharmaceuticals Inc., which have also volved earlier and ready to grant approv- GeoVax Labs Inc. BravoVax is situated in said they intend to develop a vaccine for als as applications come in. Wuhan’s Biolake, a biopharma hi-tech 2019-nCoV. (Also see “Coronavirus: Can Meanwhile, Chinese traditional medi- park which also hosts one of Pfizer Inc.’s Companies Achieve Vaccine Ambition? “ - cine ShuangHuanglian has sold out over- main R&D centers in China. Scrip, 28 Jan, 2020.) night in China after the product was said BravoVax will provide development to inhibit viral replication, although there support, including testing and manufac- Published online 3 February 2020 Atriva Fast Tracks Antiviral Candidate As Coronavirus Arrives In Germany

ANDREW MCCONAGHIE [email protected]

MEK inhibitor drug which started life as a Pfizer Inc. on- Atriva told Scrip that it was currently working with the Charité cology candidate might be an effective antiviral therapy University Hospital in Berlin to access samples of the virus and Aagainst coronavirus 2019-nCoV. carry out preliminary lab tests of the drug. Atriva Therapeutics GmbH is a start-up pharma company based A total of four people have been confirmed with the infection in in Tübingen, Germany, and is developing its lead candidate ATR- Germany, and are being treated in an isolation ward in a hospital 002 for use as a novel antiviral treatment for seasonal influenza, in Munich. for which it has successfully completed Phase I safety trials. Atriva’s CEO Dr Rainer Lichtenberger told Scrip: “We are inten- Now the company has sprung into action as the coronavirus sively talking to Charité to perform the testing as soon as enough threat escalates, and is looking to establish if its candidate could viral material has been received, either from the cases in Bavaria help treat patients infected with the novel virus. or material Charité would receive from China and then propagate. The company, set up by virology experts in 2015, is joining oth- “In principal MEK inhibitors have a positive influence on coro- er firms such as J&J who are responding to the deadly outbreak, navirus, but that is yet to be shown with ours,” he said, and added and considering vaccines or anti-viral therapies which might be that his company would ramp up preclinical work if early tests developed in record time. Read the full article here produced encouraging signs. Atriva is led by CEO Rainer Lichtenberger, who co-founded the company with Professor Oliver Planz, an expert in antiviral re- search at the university of Tübingen. The company is aiming to avoid the problem with existing therapeutic antivirals, which either only treat the symptoms of influenza or target proteins on the surface of viruses – a mecha- nism that leaves the door open to drug-resistant mutations in the virus. MEK inhibitors – such as Novartis AG’s Mekinist () – work by blocking the mitogen-activated protein kinase inside cells, a key pathway in cell division. In tumors such as melano- ma this blocks the creation of new cancer cells, but Atriva has shown that its candidate can also block the replication of a virus inside cells. Atriva says that the difference is that against viral infection, a MEK inhibitor need only be administered for a short five-day period-long enough to block the virus replication, but not long enough for it to cause any of the adverse events seen in cancer treatment, which is much longer and in higher doses.

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Lichtenberger pointed out the problem of drug-resistant strains is seen in Roche’s neuraminidase inhibitors, off-patent Coronavirus Coverage Tamiflu (oseltamivir) and also its newly-launched follow-up Xo- China Coronavirus Cases Up Sharply As Pharma fluza (baloxavir). Rushes To Aid: https://bit.ly/2Sdu4JN Coronaviruses are distinct from the influenza virus, which in any case makes it unlikely that Roche’s products will work on the Moderna, Inovio Coronavirus Vaccine Candidates Fast- new outbreak. Tracked By International Coalition: https://bit.ly/2ScWHXr Atriva has completed a Phase I trial confirming ATR-002’s safety VGXI Gears To Support Production Of New and tolerability against influenza, and is preparing for Phase II tri- Coronavirus Vaccine: https://bit.ly/2Ul9c5M als in time for the next flu season in late 2020. Coronavirus: Can Companies Achieve Vaccine Like other smaller companies responding to the coronavirus Ambition?: https://bit.ly/2vQMOY5 emergency, Atriva could stand to benefit from the extra invest- Virus Stresses China As Emerging Initial Response ment available in the field when viral outbreaks occur. Provokes Anger: https://bit.ly/399qQhh The company has been invited to present its platform to the US Biomedical Advanced Research and Development Au- Cipla Gears To Step In With Gx Kaletra Supplies thority (BARDA) later this year, a possible source of significant For nCoV: https://bit.ly/2SeoB5u non-dilutive funding to add to the company’s private fund- Epidemic Expert Kang On Tackling nCoV And raising rounds. Science As A Leveler: https://bit.ly/2H4o0hD Published online 29 January 2020 JT Gains World-First Topical JAK Inhibitor Approval IAN HAYDOCK [email protected]

apan has granted the first approval helps prevent the over-activation of was also approved for atopic dermatitis worldwide for a Janus kinase (JAK) in- immune responses. in Japan back in 1999. Jhibitor in topical form, issuing a nod JT said the approval was based on a Outside Japan, delgocitinib was li- for Japan Tobacco Inc.’s Corectim (delgoci- Phase III study in Japan that showed the censed globally to Leo Pharma AS in late tinib; JTE-052) in the second-line treat- percentage change in mEASI (modified Ec- 2014 for topical dermatology uses (includ- ment of adult atopic dermatitis. zema Area and Severity Index) score from ing atopic dermatitis), and has also been Also newly approved in the country is baseline was superior to placebo, although licensed to Rohto Pharmaceutical Co. Bayer AG/Orion Corp.’s prostate cancer it did not provide detailed findings. Ltd. for development and commercializa- drug Nubeqa (darolutamide), for the non- tion in Japan for ophthalmology disorders. metastatic, castration-resistant form of LIMITED JAPAN COMPETITION? Leo presented positive top-line results the disease. While JT/Torii face competition globally in in second-line (post-steroid) chronic The marketing clearance for Corectim the topical JAK inhibitor space, the main hand eczema (similar and often overlap- 0.5% ointment paves the way for a new potential rival molecules for atopic der- ping to atopic dermatitis) to the 2019 treatment modality in the sector, at least matitis do not currently appear to be in American Academy of Dermatology in patients unresponsive to standard first- development in Japan. meeting, which showed “46% of patients line steroid therapy. These include Incyte Corp.’s ruxolitinib in the 30mg/g BID [twice a day] delgoci- The drug, which stems from the tobacco in Phase III and Asana BioSciences LLC’s tinib ointment group achieved ‘clear’ or company’s in-house research, follows an oral dual JAK/SYK inhibitor ASN002, in ‘almost clear’ skin, based on physician’s approval filing a year ago in January 2019. Phase IIb for both severe chronic hand ec- global assessment, compared to 15% on Under a late 2016 deal, JT’s commercial af- zema and atopic dermatitis. placebo at eight weeks.” filiate Torii Pharmaceutical Co. Ltd. co-de- Eli Lilly & Co./Incyte’s oral JAK inhibitor JT/Torii are also conducting a local veloped and will commercialize the mole- Olumiant (baricitinib) is also being devel- Phase III development program designed cule for topical dermatology applications in oped globally for atopic dermatitis but has to expand the approved indications to the country, where atopic dermatitis preva- not been approved in Japan for this use. atopic dermatitis in pediatric patients lence has been estimated at around 7%. In other classes, the indication has aged 2-16. A recent report on the indication from seen multiple new therapies including Datamonitor Healthcare predicts the Sanofi/Regeneron Pharmaceuticals Inc.’s BAYER’S NUBEQA FOR number of patients in Japan will reach interleukin-4 and -13-targeting antibody PROSTATE CANCER around 5.5 million in 2025. Dupixent (dupilumab), approved in Ja- Bayer/Orion’s Nubeqa, an androgen re- JAK plays a central role in immune pan two years ago for second-line use. A ceptor inhibitor, was granted a marketing activation cell signaling suppresses topical form of Astellas Pharma Inc.’s im- authorization by Japan’s regulators for the and delgocitinb as a pan-inhibitor munosuppressant Prograf (tacrolimus) treatment of non-metastatic castration-

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resistant prostate cancer (nmCRPC), based Bayer has said it sees darolutamide as on the 1,500-patient Phase III ARAMIS trial being competitive with other earlier-to- evaluating darolutamide plus androgen market therapies helped by its safety pro- deprivation therapy (ADT) compared to JAK plays a central role file in the ARAMIS trial. placebo plus ADT. in immune ac­tivation cell The trial showed a highly significant NEW INDICATIONS improvement in the primary efficacy signaling suppresses and Also approved were a variety of prod- endpoint of metastasis-free survival, with ucts in new indications including Mo- a median 40.4 months for darolutamide del­gocitinb as a pan- chida Pharmaceutical Co. Ltd.’s Dinagest plus ADT versus 18.4 months for placebo inhibitor helps prevent (dienogest; licensed from Jenapharm plus ADT (HR=0.41, 95% CI 0.34-0.50; GMBH) for dysmenorrhea, which has P<0.001). the over-activation of been marketed for endometriosis since The drug is already approved in the 2008 and was expanded to adenomyo- US and Brazil (under the same brand immune responses. sis pain in 2016. name) and filings in the EU and other Eisai Co. Ltd.’s epilepsy drug Fycompa markets are underway or planned, and (perampanel) has been approved for for is also being investigated for metastatic monotherapy of partial-onset seizures hormone-sensitive prostate cancer in and partial-onset seizures in pediatric pa- the Phase III ARASENS program. tients four years of age or older, and in a NmCRPC patients are often asymptom- new fine granule formulation. atic and the Bayer pointed to an increasing The newly approved new drugs includ- number of prostate cancer cases in Japan, ing Corectim and Equba are expected to where over 89,000 men are estimated to tamide) was launched for metastatic CRPC be included in Japan’s reimbursement be diagnosed with the disease annually, in Japan in 2014 and Janssen Pharma- price list, which allows nationwide launch making it the second most-common male ceutical Cos./Nippon Shinyaku Co. Ltd.’s through the national health insurance malignancy after stomach cancer. Erleada (apalutamide) was approved for scheme, around April. Elsewhere in the sector, Astellas’s an- CRPC without distant metastases in the drogen receptor inhibitor Xtandi (enzalu- country in March 2019. Published online 27 January 2020 Surprise! Pfizer And Lilly File Tanezumab For Pain With FDA Despite Safety Questions

JESSICA MERRILL [email protected]

shown modest efficacy and still had safety issues in clinical trials. Pfizer and Lilly have also studied tanezumab at a higher 5mg dose in osteoarthritis and even at a 10mg dose in patients with chronic low back pain. The commercial outlook for tanezumab hasn’t been good, and investors have largely written the product off because NGF inhibitors have been associated with a higher rate of joint safety events versus non-steroidal anti-inflammatory drugs in clinical tri- als. Nonetheless, the need for non-opioid medications to relieve chronic pain is substantial. fizer Inc. and Eli Lilly & Co. have filed the first nerve growth “There is just a huge amount of unmet need in this patient factor (NGF) inhibitor, tanezumab, with the US Food and population,” Biopharmaceuticals group president Angela Hwang PDrug Administration for the treatment of pain in patients said during the earnings call. “Patients are cycling through a with moderate-to-severe osteoarthritis. Pfizer confirmed the De- number of pain medications, and there just is an incredible need cember filing during the company’s fourth quarter sales and earn- for new options, and this is where we think tanezumab can re- ings call on 28 January. ally fill an unmet need.” There are about 27 million osteoarthritis The path to market for NGF inhibitors has been uncertain be- patients in the US, about 11 million of whom have moderate-to- cause of the challenging safety profile of the drugs, but Pfizer severe disease. Hwang said 80% of those 11 million people have said it collaborated closely with the FDA on the filing. The regula- tried and failed three or more analgesics. Pfizer and Lilly are also tory filing was for the lower 2.5mg dose of tanezumab, which has pursuing regulatory filings in Japan and Europe, she added.

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Regeneron Pharmaceuticals Inc. and Teva Pharmaceutical While the 5mg treatment arm met two of three co-primary effi- Industries Ltd. have also been developing an NGF inhibitor, cacy endpoints at 16 weeks, patients who received 2.5mg did not fasinumab, in late-stage development, with similar questions experience a statistically significant improvement in pain, physical around the safety and efficacy balance. The companies ex- function or patients’ overall assessment of their OA at 16 weeks pect data from a Phase III osteoarthritis trial to read out in the compared to NSAIDs. third quarter. Meanwhile, there was a statistically significant higher rate of The class of drugs has a long development history, after having joint safety issues in both tanezumab arms compared to NSAIDs been placed on clinical hold in 2010 when the first big safety sig- at 80 weeks. Joint safety was measured as a composite that in- nals emerged in clinical trials. cluded adjudicated outcomes of rapidly progressive osteoarthritis AstraZeneca PLC and Johnson & Johnson ultimately decided (RPOA) type 1 or type 2, subchondral insufficiency fracture, osteo- not to move forward with development of their NGF inhibitors. necrosis or pathological fracture. (Also see “J&J, Regeneron follow Pfizer in clinical holds for anti- In an earlier Phase III osteoarthritis trial, tanezumab provided NGFs” - Scrip, 30 Dec, 2010.) significant efficacy improvements for patients at both doses on Last year, Pfizer and Lilly reported data from a Phase III trial of several efficacy endpoints. (Also see “Pfizer/Lilly’s Tanezumab Re- tanezumab designed to compare the long-term joint safety and duces Osteoarthritis Pain, But Is It Safe?” - Scrip, 18 Jul, 2018.) Tan- 16-week efficacy of tanezumab to NSAIDs in patients with mod- ezumab has also been studied for the treatment of chronic low erate-to-severe osteoarthritis of the hip and knee. That data led back pain and cancer pain. [Editor’s note: Pfizer has clarified that it several analysts to declare the class of drugs commercially dead. has completed Phase III trials in chronic low back pain; cancer pain (Also see “Lilly/Pfizer’s Tanezumab Safety Takes A Hit With Latest is still listed as in Phase III in the pipeline update released 28 Jan.] Phase III Results” - Scrip, 19 Apr, 2019.) Published online 29 January 2020 Brilinta Boost For AZ In Stroke Study KEVIN GROGAN [email protected]

ales of AstraZeneca PLC’s Brilinta are the European Society of Cardiology an- SOCRATES failure, but testing a slightly dif- set to expand after the anticoagu- nual congress in Paris in September 2019, ferent hypothesis using the Brilinta/aspirin Slant finally demonstrated benefit showed that the Brilinta/aspirin combina- combo for a shorter duration of time has over aspirin in preventing stroke in a large tion reduced the relative risk of a composite paid off. He added that detailed results of late-stage trial. endpoint event (cardiovascular death, heart the increased incidence of bleeding events The UK firm has announced topline re- attack, or stroke) by 10% compared with as- “will have to be factored in to get a full as- sults from the Phase III THALES study which pirin alone; a subgroup of patients with pre- sessment of the market opportunity.” showed that Brilinta (ticagrelor) 90mg, vious percutaneous coronary intervention Brilinta, which is also indicated for pa- used twice daily and taken with aspirin for (PCI) saw a better than average response, tients with a history of myocardial infarction 30 days, reached a significant and clinically with a 15% reduction on the endpoint. and a high risk of developing an athero- meaningful reduction in the risk of the pri- The THALES results went down well thrombotic event, is a big earner for As- mary endpoint of stroke and death, com- with analysts and SVB Leerink issued a traZeneca and third quarter revenues rose pared with aspirin alone. The trial included note on 27 January stating that the pre- 27% to $416m. However, the drug has not more than 11,000 patients with minor liminary safety data were consistent with reached the commercial potential set out acute ischemic stroke or high-risk transient the known safety profile for the drug. by CEO Pascal Soriot when he was fighting ischemic attack (TIA) randomized to treat- While there was an increased bleeding off the attentions of Pfizer back in 2014. ment within 24 hours of symptom onset rate in the treatment arm, “we view Bril- Nearly six years ago, Soriot said Astra- The full THALES results will be present- inta success in stroke as an important ad- Zeneca forecast that Brilinta would have ed at a forthcoming medical meeting but dition to the label.” sales of $3.5bn in 2023 but the firm admit- they represent something of a turnaround Over at Jefferies, analyst Peter Welford ted in 2016 that the target was unattain- in fortune for Brilinta in stroke. issued a note saying that there are about able. The lowering of guidance came after Some four years ago, the SOCRATES trial 2.2 million ischemic stroke patients in ma- the SOCRATES blow and results from the evaluated treatment with Brilinta alone jor markets, “a substantial expansion over EUCLID trial where Brilinta did not show a compared with aspirin in the same type the current acute coronary syndrome in- benefit compared with the older, generic of patients as THALES but over a longer dication” for the P2Y12 receptor agonist blood thinner clopidogrel in treating pe- period (90 days). The primary efficacy of about 4.3 million patients. He forecast ripheral artery disease. endpoint of time to first occurrence of an $2.5bn in worldwide peak sales, assuming Nevertheless, Brilinta is still a key driver event such as stroke, heart attack or death patent expiry by 2024. for AstraZeneca’s CVRM (cardiovascular/ was not met in SOCRATES. Bryan Garnier analyst Eric Le Berrigaud renal medicine) franchise. One of the other AstraZeneca had better luck with the noted that the THALES success was far products for which the firm has high hopes THEMIS trial. That study, presented at from being taken for granted given the in that area is the diabetes pill Farxiga

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(dapagliflozin) for the treatment of heart In an interview with Scrip at the J.P. killer in the world is still cardiovascular failure and the US Food and Drug Admin- Morgan Healthcare conference in San disease by far.” istration recently granted a priority review Francisco last month, AstraZeneca bio- AstraZeneca noted that stroke is the for the therapy for the reduction of cardio- pharmaceuticals president Ruud Dob- second leading cause of death world- vascular death or worsening of heart fail- ber noted that “there is a lot of attention wide, with 6.2 million stroke-related ure in adults with reduced ejection fraction [on] the breakthroughs in oncology but deaths in 2017. both with and without type 2 diabetes. we need to understand the number one Published online 28 January 2020 Atopic Dermatitis: Ruxolitinib And Baricitinib Spearheading New Therapies

JOHN DAVIS [email protected]

ncyte Corp. is expecting clinical data inhibitor, abrocitinib, and AbbVie Inc.’s limit its usefulness among dermatologists. later this quarter from a second pivotal Rinvvoq (upadacitinib). Topical ruxolitinib is also targeting a differ- Istudy, TRuE-AD1, of its topical formula- ent patient population, mild-to-moderate tion of JAK inhibitor, ruxolitinib, in mild- RUXOLITINIB CLINICAL DATA atopic dermatitis, compared with the to-moderate atopic dermatitis, and the Incyte reported on 28 January top-line moderate-to-severe population targeted company says it is committed to develop- data from its first-to-report pivotal Phase by Dupixent. ing ruxolitinib cream as a first-line option III study, TRuE-AD2, showing that topical But the analysts were looking forward for the condition. ruxolitinib cream met its primary endpoint to the results of the TRuE-V trials of topi- The competitive pressure to become a in mild-to-moderate atopic dermatitis. cal ruxolitinib in vitiligo, a condition with contender in the atopic dermatitis market Significantly more patients treated with higher unmet need, which are expected ticked up this week, with the US biotech ruxolitinib cream 0.75% and 1.5% achieved to read out in 2021. announcing the bare of positive IGA (investigational global assessment) At the recent J. P. Morgan meeting, In- top-line clinical data from another first scores of 0 (clear) or 1 (almost clear), with cyte chairman, president and CEO, Hervé Phase III study, TRuE-AD2, of topical ruxoli- at least a two-point improvement from Hoppenot remarked that one potential tinib, on 28 January. baseline at week 8, than patients treated differentiating effect of topical ruxoli- Meanwhile, Eli Lilly & Co. announced on with a control cream, in the 600-patient tinib seen in earlier clinical studies was its 27 January positive top-line results from study in adolescents and adults. quick effect – a matter of hours – on itch- a Phase III study, BREEZE-AD4, of the oral The safety data was consistent with ing, an important factor from a patient’s JAK1/2 inhibitor, Olumiant (baricitinib, li- previous data, Incyte added. Ruxolitinib is standpoint. He also noted that two Phase censed worldwide from Incyte), and cur- already marketed as an oral formulation, III studies of topical ruxolitinib in vitiligo rently marketed for rheumatoid arthritis. Jakafi tablets (Jakavi in the UK), for the were due to report in 2021. Incyte intends On 30 January, positive top-line results from treatment of myelofibrosis, polycythemia to market its dermatology portfolio direct- the BREEZE-AD5 were also announced. vera and graft-versus-host disease. ly in the US, and is creating a new division, From Japan, news came that Japan To- The TRuE-AD2 study enrolled patients of around 150 people, to do that. bacco Inc.’s topical JAK inhibitor, Corectim with at least two years’ history of atopic (delgocitinib), has been approved for the dermatitis, with symptoms that included LILLY’S BARICITINIB second-line treatment of adult atopic der- itchy, oozing and crusty skin lesions, and Meanwhile, Lilly and Incyte reported top- matitis in that country. IGA scores were assessed after twice-daily line results from its Phase III study, BREEZE- These drugs are not alone in targeting application of the creams. AD4, indicating the oral once-daily JAK in- the market opportunity in atopic derma- A US new drug application could be hibitor met its primary endpoint of at least titis, shown to be attractive for innovators submitted for ruxolitinib cream in the a 75% improvement in skin inflammation, by the in-roads Sanofi/Regeneron Phar- second half of 2020, if the second Phase when added to topical steroids in adult pa- maceuticals Inc.’s dual IL-4/IL-13 inhibitor, III study is also positive; results from the tients with moderate-to-severe atopic der- Dupixent (dupilumab), has made in the TRuE-AD1 are expected later this quarter. matitis not controlled with cyclosporine. moderate-to-severe atopic dermatitis The product could be launched in 2021, The study is so far the only to report segment. Sanofi also has plans to expand with SVBLeerink analysts forecasting peak involving the use of a JAK inhibitor in into the milder disease segment. sales of around $1.1bn. patients who have failed cyclosporine There are numerous candidate atopic Analysts at Credit Suisse noted that therapy, and no venous thromboembolic dermatitis therapies nearing the mar- the TRuE-AD2 study was not designed to events or deaths were reported in the trial ketplace, including AstraZeneca PLC’s show relative efficacy versus the standard- – there have been concerns about throm- tralokinumab, Pfizer Inc.’s selective JAK1 of-care, topical corticosteroids, which may boembolic events in previous studies.

20 | Scrip | February 7, 2020 © Informa UK Ltd 2020 RESEARCH & DEVELOPMENT/STOCKWATCH

The primary endpoint, EASI75, at week 16, was met by 31.5% dose also met secondary IGA and itch endpoints. In contrast, a of patients treated with 4mg doses of baricitinib, significantly dif- 1mg dose of baricitinib had a non-significant effect on EASI75 ferent to the 17.2% of patients responding to placebo, while the compared with placebo. endpoint was not significantly different in patients treated with Baricitinib has been submitted for regulatory review in the 1mg and 2mg doses of baricitinib. Side effects included nasophar- EU in moderate-to-severe atopic dermatitis, and Lilly said that yngitis, headache and influenza. US and Japan submissions were expected this year. The US big On 30 January, Lilly and Incyte announced a 2mg dose of pharma announced earlier this month it was paying $1.1bn baricitinib for 16 weeks met the primary endpoints of at least a to acquire the US biotech,Dermira Inc., which has a candidate 75% improvement in skin inflammation in moderate-to severe monthly injectable IL-13 inhibitor, lebrikizumab, in Phase III atopic dermatitis in the BREEZE-AD5 study. The improvement studies for atopic dermatitis.. was significantly different to that seen with placebo. The 2mg Published online 31 January 2020 Stockwatch: Biosimilars And Dividends Connect Earnings At Pfizer And Roche

ANDY SMITH [email protected]

ith Brexit and coronavirus de- analysts’ consensus estimates of revenue divisions, companies like GlaxoSmithKline pressing markets over the and adjusted EPS. PLC and Pfizer will drastically cut the free Wweek, earnings season for life Nothing short of consensus beating cash flow available for distribution by divi- science companies shifted into a higher revenues, EPS and guidance together dends and compensate for this with their gear with a number of big companies re- could have bolstered Pfizer’s stock price drug discovery, development and market- porting. In time, the effects of Brexit and in a market that became more worried ing prowess. This could end up being a 2019-nCoV are likely to subside, but the about coronavirus as the week went circular argument since when companies double-edge sword of biosimilar com- along. On the day of its earnings an- have challenges like the all too frequent mercialization continues to rise from the nouncement, Pfizer’s stock price was product failure, the first thing to be affected full-year financial reports of Pfizer Inc. and marked down about 1% in the premar- after the press release is the dividend. Roche. ket, finishing down just over 2% on that Unlike Johnson & Johnson’s (J&J’s) re- day and just under 5% for the week, BIOSIMILARS CUT BOTH WAYS cent earnings report, which modestly which had been a tough one for equities. There is a certain prophetic echo to the disappointed on the first and last of the This was against the NSYE ARCA Pharma- imminent divestment of Pfizer’s Upjohn three key financial metrics (revenue, earn- ceutical Index’s 1% weekly drop. established (and declining) pharmaceuti- ings and guidance), Pfizer’s 9% fall in cals business to Mylan NV, and the sales of 2019 fourth-quarter revenues to $12.7bn DIVIDEND FRAGILITY Pfizer’s biosimilar business. (Also see “Pfizer fractionally beat analysts’ consensus esti- The trouble with focusing on three sup- Delivers On Biosimilars Strategy” - Gener- mates of $12.6bn. posedly tried and trusted metrics is that ics Bulletin, 31 Jan, 2020.) Pfizer’s biosimilar The revenue fall was largely down to the other “known unknown” metrics can of- franchise generated $911m in 2019, but it old enemy of the branded pharmaceutical ten rise to prominence. In recent years is a franchise of two parts. Europe has had company: generic competition to a small Pfizer has divested its animal health and biosimilar versions of J&J’s Remicade (inflix- molecule former blockbuster. In Pfizer’s nutrition divisions. With the Upjohn es- imab) since 2013 and the convergence of case, the culprit was the 67% year-on-year tablished pharmaceutical business, and single payer markets with the acceptance fall in sales of the anti-epileptic Lyrica (pre- consumer joint venture also scheduled of extrapolation (approved biosimilars can gabalin). Pfizer has segmented its three for departure, the remaining core bio- be prescribed for all the innovator products’ divisions – Biopharmaceuticals, Upjohn pharmaceuticals business remains a very indications, without additional clinical stud- and Consumer Healthcare – as a prelude different investment proposition from the ies) together with the near-universal use of to their separation. The loss of exclusiv- Pfizer of seven years ago when viewed tenders, has made Europe a race to the bot- ity for Lyrica contributed to a 32% and an in the light of two other metrics: risk and tom in biosimilar pricing. The fragmented 18% fall in Upjohn’s divisional sales in the dividend yield. US payer and contracting market, however, fourth quarter and full year, respectively. Big pharma companies’ stocks are held by with its open-door policy on patent exten- Pfizer’s adjusted earnings per share (EPS) pension and insurance companies for their sions, is still in the early innings for biosimi- of 55 cents, which declined by 13% from defensive dividend flow in order to meet lars pricing. Pfizer’s ex-US biosimilar busi- the fourth quarter of 2018, easily missed pension liabilities and policy claims, respec- ness saw an 8% fall in 2019 sales as multiple analysts’ estimates of 58 cents. Pfizer’s full- tively. In the process of divesting them- competitors and aggressive tendering bit. year 2020 guidance, however, bracketed selves of slower-growing and less profitable TURN TO PAGE 23

scrip.pharmaintelligence.informa.com February 7, 2020 | Scrip | 21 PIPELINE WATCH

Scrip’sPipeline weekly Pipeline Watch Watch tabulates- 24-30 the most January, recently reported 2020 late-stage clinical trial and regulatory developments from the more Click here for the entire pipeline than 10,000 drug candidates currently under active research worldwide. with added commentary: Phase III http://bit.ly/2mx4jY3

PIPELINESearch WATCH, 24–30 JANUARY 2020

Change Lead LOA Event Type Drug Name Indication Comments To LOA Company/Partner (%) (%) Phase III Top- Olumiant Atopic Eli Lilly & Co/Incyte BREEZE-AD4; Met 0 71 Line Results (baricitinib) Dermatitis Primary Endpoint Phase III Top- Brilinta THALES; Met AstraZeneca PLC Ischemic Stroke 0 52 Line Results (ticagrelor) Primary Endpoint Phase III Top- ruxolitinib TRuE-AD2; Met Incyte Corporation Atopic Dermatitis 6 68 Line Results Cream Primary Endpoint Phase III Top- Olumiant Atopic Dermatitis, BREEZE-AD5; Met Eli Lilly & Company 0 71 Line Results (baricitinib) Monotherapy Primary Endpoints Phase III Top- Ono/Bristol-Myers Opdivo Ovarian Cancer, ONO-4538-23; Missed -3 32 Line Results Squibb (nivolumab) Refractory Primary Endpoint Phase II/III Top- olipudase Niemann-Pick ASCEND; Improved Sano 0 65 Line Results alfa Disease Lung Function Phase III BGB-290-303; Protocol BeiGene pamiparib Gastric Cancer -25 10 Converted To Phase II Amendment Fibrodysplasia Phase III Trial MOVE; Following Ipsen SA palovarotene Ossicans -15 49 Dosing Paused Futility Analysis Progressiva NuTide:121; Plus Phase III Trial Biliary Tract NuCana plc Acelarin cisplatin, Versus 29 35 Initiation Cancer, First-Line gemcitabine Phase IIIb Trial Alzheimer's Re-Dosing Open-Label Biogen, Inc. aducanumab 0 38 Announcement Disease Extension Study Phase III Trial Albireo Pharma, odevixibat Biliary Atresia Global Pivotal Trial 0 24 Announcement Inc. Source: Biomedtracker | Informa, 2020 Source = Biomedtracker; LOA = Biomedtracker's opinion on likelihood of approval.

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CONTINUED FROM PAGE 21 regional biosimilar tender process. This some Nordic European markets are now Biosimilars are also proving to be a often has no firm contractual period and 100% biosimilar. The US has the lowest double-edged sword for the company. It the tender can end as soon as a cheaper prices for small molecule generic drugs reported an 18% fall in Amgen Inc.’s anti- offer comes along. Core operating profit (which comprise over 90% of US scripts), inflammatory Enbrel (etanercept) – which rose 10%, modestly beating analyst’s es- so when patent term extensions on bio- it markets outside the US – due to biosimi- timates, while further down the income logics eventually expire, pricing is likely to lar competition. All this could make Pfiz- statement, Roche’s net profit rose by 30% mimic that in Europe. That is unlikely to er’s ex-US biosimilars business the next thanks to the absence of goodwill write- be good for dividends. candidate for divestment. downs, which depressed profit a year ear- Andy Smith gives an analyst and former In contrast to the Pfizer sales decline, lier. On balance, Roche’s dividend increase investor’s view on life science companies. Roche posted an 8% increase in 2019 rev- was probably the prop that ensured that He joined the research house Equity De- enues, but unlike Pfizer, Roche modestly its share price ended the week roughly velopment in October 2019 having pre- missed analysts’ consensus revenue esti- where it had started. viously been an analyst at Edison group mates. The shortfall of course, came from Behind the headlines of growing bio- and a Senior Principal in ICON PLC’s Com- biosimilar competition to some of Roche’s similar franchises at big pharma and mercialization, Pricing and Market Access former biologic oncology blockbusters biotech companies is the tacit observa- consulting practice. Andy has been the lead Herceptin (trastuzumab), Rituxan (ritux- tion that eventually, European pricing fund manager for four life science–specific imab) and Avastin (bevacizumab). The dynamics – multiple biosimilar manufac- funds, including 3i Bioscience, Internation- management commentary emphasized turers jostling in an aggressive tendering al Biotechnology and the AXA Framlington new products taking up the slack caused scrum for the sole supply to large payers Biotech Fund, was awarded the techMark by biosimilar competition, although – will predominate. In these situations, Technology Fund Manager of the year for the suggestion that the worst had likely the authorized biosimilar is usually left 2007 and was a global product manager at passed in Europe clearly meant that Roche watching the try being scored from the SmithKline Beecham Pharmaceuticals. had not yet come up against the Italian other end of the pitch. In consequence, Published online 3 February 2020

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