Spotlight on Market Access Actionable Understandings from AIS Health’S In-Depth Coverage

Spotlight on Market Access Actionable understandings from AIS Health’s in-depth coverage

September 16, 2019 Recent Situations Stress That Data Is More Important Than Ever to FDA, Drug Uptake 2 Clinical Trials by Indication: Q2 2019 A pair of drugmakers and the FDA found themselves in the news lately, but it’s safe to say it wasn’t for the reasons they would prefer. Both situations Reality Check: PCSK9 Inhibitors 8 stress the importance of data needed to secure product approvals, and, perhaps, payer and provider uptake.

On Aug. 6, the FDA put out a statement addressing “data accuracy issues” with Zolgensma (onasemnogene abeparvovec-xioi), a new gene therapy to treat spinal muscular atrophy in people less than 2 years old who have bi-allelic mutations in the survival motor neuron 1 gene, including those who are presymptomatic when diagnosed.

The one-time therapy has the distinction of being the most expensive drug in the world, with a price tag of $2.1 million.

The FDA approved the drug from AveXis, Inc. on May 24 (SMA 7/1/19, p. 6). On June 28, AveXis — which was acquired by Novartis AG last year — notified the agency that there was “a data manipulation issue that impacts the accuracy of certain data from product testing performed in animals submitted in the biologics license application (BLA) and reviewed by the FDA.” continued on p. 3

Report Reveals That Almost 100 RM/AT Products Are in Phase III Clinical Trials

This past quarter saw two new gene therapies: Novartis AG subsidiary AveXis, Inc.’s Zolgensma (onasemnogene abeparvovec-xioi) received FDA approval May 24 for the treatment of spinal muscular atrophy (SMA 7/1/19, p. 6), and bluebird bio’s Zynteglo (autologous CD34+ cells encoding βA-T87Q- globin gene) received conditional marketing authorization from the Europe- an Commission for transfusion-dependent beta thalassemia.

While only a handful of therapies in the broader regenerative medicine/ advanced therapy (RM/AT) space are available globally, a new report shows that is likely to change, as there are more than 1,000 products in the pipeline. Many of these therapies truly are innovative products, but they don’t come cheap and often have complex reimbursement schemes that some payers and providers are struggling with, an issue that will need to be handled soon as more of these therapies are poised to hit the market.

The Alliance for Regenerative Medicine published ◊ 249 cell therapy trials are proceeding: 49 the report, titled Quarterly Global Regenerative Med- are in Phase I, 168 are in Phase II, and 32 are in icine Sector Report: Q2 2019, on Aug. 1. It shows there Phase III. are 1,069 clinical trials using specific RM/AT technol- ◊ 44 tissue engineering trials are happen- ogies, which include gene therapy, gene-modified cell ing: five are in Phase I, 23 are in Phase II, and 16 therapy, cell therapy and tissue engineering. Ninety- are in Phase III. four of those products are in Phase III trials. They also span a variety of indications (see chart More specifically, the report reveals: below). ◊ 366 gene therapy clinical trials are un- While Zolgensma’s $2.125 million price for a derway: 117 are Phase I, 219 are Phase II, and one-time infusion makes it the costliest drug on the 30 are Phase III. planet, other newer RM/AT products are certainly ◊ 410 gene-modified cell therapy trials are not cheap. Spark Therapeutics Inc.’s Luxturna (vore- ongoing: 187 are in Phase I, 207 are in Phase II, tigene neparvovec-rzyl), approved in December 2017 and 16 are in Phase III. for a rare form of blindness, costs $425,000 per eye;

Clinical Trials by Indication: Q2 2019

• 643 (60%) of all current clinical trials are in oncology, including leukemia, lymphoma, and cancers of the brain, breast, bladder, cervix, colon, esophagus, ovaries, pancreas, and others.

• 60 (6%) are in cardiovascular disorders, including congestive heart failure, myocardial infarction, critical limb ischemia, heart disease, and others.

• 57 (5%) are in diseases of the central nervous system, including multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, traumatic brain injury, ALS, and others.

SOURCE: Alliance for Regenerative Medicine, Quarterly Global Regenerative Medicine Sector Report: Q2 2019, released August 2019. Download the report at https://alliancerm.org/?smd_process_download=1&download_id=4962.

Novartis Pharmaceuticals Corp.’s chimeric antigen not in place to have the ability to track the patient once receptor T-cell (CAR-T) therapy Kymriah (tisagenlec- therapy is administered.” leucel), first approved in August 2017, costs $475,000 Download the report at https://bit.ly/31cvh6W. G or $373,000 depending on the type of cancer it’s used in; and Gilead Sciences, Inc. unit Kite Pharma, Inc.’s by Angela Maas Yescarta (axicabtagene ciloleucel), approved in October This story was reprinted from AIS Health’s monthly 2017 to treat large B-cell lymphoma, costs $373,000. publication RADAR on Specialty Pharmacy. For more Many of these products’ manufacturers are offering information, visit https://aishealth.com/product/ various reimbursement schemes, including rebates if a specialty-pharmacy. therapy doesn’t work, other outcomes-based deals and multiyear pay-over-time payment options. But experts Issues Stress Data’s Importance note that many barriers to successfully executing these continued from p. 1 deals exist. According to a July 26 memorandum by Wilson “In principle, spreading the cost over a five-year W. Bryan, M.D., director of the FDA’s Office of Tissues period and putting the cost installments at risk based and Advanced Therapies, “AveXis appears to have upon efficacy is a good approach,” says Winston Wong, become aware of the data manipulation as early as Pharm.D., president of W-Squared Group, about March 14, 2019,” but rather than informing the agency, Zolgensma. “However, the devil is in the details. Do we which was evaluating Zolgensma’s BLA at the time, the have the systems in place that have the capability to company first conducted its own internal investigation, administer a five-year contract?” reporting its findings to the FDA after the investigation was completed. Had the FDA known of the issue before “In principle, spreading the cost over it approved Zolgensma, “I believe that the approval would have been delayed” beyond its Prescription Drug a five-year period and putting the cost User Fee Act (PDUFA) date of May 31, he wrote, add- installments at risk based upon efficacy ing that he believed the FDA still would have approved is a good approach.” the BLA. “Based on the information available at this time, In addition, he asks, “Who is responsible for the the Phase 3 clinical trial results continue to provide billing of the installment, and who is actually making compelling evidence of the effectiveness of Zolgensma, the annual payment? Is it the insurance carrier in all along with sufficient evidence of safety to support an cases, or is that passed on to the self-funded employer? overall favorable benefit-risk profile,” wrote Bryan. Under the payment installment option, how does the “It is the manufacturer’s responsibility to sub- provider, who has to obtain the product, get reim- mit complete and accurate information in marketing bursed?” applications for evaluation by the FDA. If we become According to Wong, “We do not have the systems aware of a concern with data submitted to the agency in place to handle the tracking and processing of as part of our review of a product application, it is in installment billing over a period of five years, as well the best interest of patients, their caregivers, and the as having the ability to track patients once they have public that we disclose such information, to the extent left the health plan,” which “will be a major obstacle permitted by law,” said the FDA in its statement. It to overcome for any value-based agreement where said that it “remains confident that Zolgensma should payment will be dependent upon continued efficacy remain on the market.” of the therapy. From the manufacturer perspective, a However, the agency said, it is “carefully assessing value-based contract implies that no payment would be this situation” and could “take action, if appropriate, made if the patient relapses or passes on. Systems are which may include civil or criminal penalties.” Accord-

ing to Bryan’s memo, “a complete assessment of the through all appropriate criminal, civil, and regulato- impact of the data manipulation will require additional ry actions against the company. Anything short of a investigation, discussions both internally within CBER forceful response would signal a green light to future [i.e., the FDA’s Center for Biologics Evaluation and pharmaceutical behavior.” The situation, they wrote, Research] and with AveXis, will probably require that “smacks of the pharmaceutical industry’s privilege and AveXis submit and FDA review one or more BLA sup- greed.…It is an outrage that after knowingly misleading plements, and may take at least several months.” the FDA in a rush to make a profit,” Novartis in its Aug. In response to the FDA statement, Novartis issued 6 press release refused “to acknowledge any culpability a press release Aug. 6 that read, in part, “we maintain or remorse. Instead, the company doubled down on its that the totality of the evidence demonstrating the greed-driven behavior.” product’s effectiveness and its safety profile continue to provide compelling evidence supporting an overall favorable benefit-risk profile. We remain steadfast that “Data can be bad for a few reasons.” this important treatment remain available.” It de- fended its decision to conduct an investigation before The senators also requested a written response alerting the FDA and noted that “at no time during by Sept. 1 as to why the agency withdrew a proposed the investigation did the findings indicate issues with regulation (RIN 0910-AC59) in October 2018 requiring product safety, efficacy or quality.…We have and will certain clinical trial sponsors to promptly notify the continue to work in close cooperation with the FDA to FDA of suspected data falsification. They also wanted appropriately update our submission and address any to know if the FDA will re-issue the regulation, which quality gaps identified. We are committed to ensur- was introduced initially in February 2010. That regula- ing the highest levels of transparency and integrity tion said that 45 calendar days was an appropriate time with health agencies, as well as with the patients and frame for reporting issues. providers we serve.…AveXis is committed to taking appropriate action to prevent future incidents.” At the time of the withdrawal, an FDA spokesperson told Bloomberg Law that “we have determined that Committee Called for Investigation this rule is no longer needed given other existing requirements around the integrity of clinical trial data.” But that statement did little to quell the indignation that many began to express. On Sept. 5, speaking at the Research!America 2019 National Health Forum, Sharpless addressed data On Aug. 9, Senate Committee on Finance Chair integrity, and, while he did not specifically mention Chuck Grassley sent a letter to Novartis CEO Vas Nara- Novartis, some of his comments appeared aimed at the simhan that said AveXis’ “conduct is reprehensible and company. “Data can be bad for a few reasons, but two could have an adverse effect on patients. Accordingly, important causes are sloppy, slipshod data collection the conduct ought to be investigated and, as appropri- or even data falsification. It can be difficult for the ate, punished to the fullest extent of the law.” In order FDA to tell these apart, because they differ in terms of to understand Novartis’ actions, Grassley asked for several pieces of information by Aug. 23, including all intent; that is, if data are bad because of carelessness records that relate to the company’s withholding data or because of fraud. But from one point of view, it does from the FDA, as well as all records that relate to its not matter that much whether we are dealing with internal investigation. incompetence or malfeasance, because either case can lead to a regulatory decision that harms patients.” Also on Aug. 9, five senators, including Elizabeth Warren (D-Mass.) and Bernie Sanders (I-Vt.), sent a He recalled that he had experience with the letter to FDA Acting Commissioner Ned Sharpless, submission of false data while at the National Cancer M.D., urging the agency to “use your full authorities to Institute, where he “saw some people mislead us in hold AveXis accountable for its malfeasance, including grant applications.

“So it should not be surprising to me now at FDA Thirty-five percent of the respondents said the that if people will lie to get their paper published or FDA should implement the regulation on drugmakers’ get their grant funded, then people will also lie to get reporting data in a timely fashion, while 23% were not a billion dollar medical product approved,” he contin- in favor of it. ued. While he said deception is rare, instances of it “are significant because even a few examples can damage Novartis Tried to Rectify Situation public confidence in the approval process.” After Novartis’ initial comments were widely derid- A Sept. 10 article on the Endpoints News website ed, it took a series of steps to try to rectify the situation. on results of a global group of 74 senior pharma exec- It let go AveXis employees whom it blamed for utives surveyed between Aug. 27 and Sept. 9 revealed the problematic data. One of those employees, Brian that six out of 10 “rated Novartis’ response as poor. Kaspar, the former chief scientific officer, has said that Only 14% thought it could qualify as fair.” Among he “stands proudly behind the safety and efficacy of the respondents’ comments were the following: drug that he and his team worked so hard to develop,” ◊ “At best, the response was ham handed according to a statement from his attorney covered by and tone deaf. And if true that the manipulated several news outlets. “He has cooperated with AveXis’s data did not impact patient safety or drug effica- internal investigation, and he categorically denies any cy, own the misconduct and apologize properly.” wrongdoing. He is prepared to assert his rights and defend his conduct accordingly.” ◊ “Novartis is a global pharma company and has taken a huge risk by not bringing An Aug. 17 Business Standard online article, citing this to the FDA’s attention as soon as they did the German newspaper Schweiz am Wochenende, said initial investigation. This type of behavior plays that in a call with company managers, “Narasimhan right into the hands of those who say that phar- said he is not perfect as a CEO and ‘we will all keep ma is only looking out for the bottom line and not working on it.’” patients’ well being.” On Sept. 9, according to an online article on Regu- ◊ “Novartis should have disclosed their latory Focus, Narasimhan told attendees of an investor findings to the FDA immediately and then conference that Novartis is “voluntarily and proactively cooperated with the Agency on the ongoing taking a pledge with the FDA to ensure that we will investigation. As it was, the timing of disclosure inform them within five business days of any credible and their ensuing explanations reflected very allegation related to data integrity.” He also said that poorly on Novartis.” the company has responded to the agency and is providing it with requested documents. And he reiterated ◊ “A bit of mea culpa would have gone a that the issue “does not impact the safety, efficacy or long way. We all get that the data issue was quality of Zolgensma.” inconsequential. That is not the point. The point “This is a unique situation,” observes Jayson Slot- is the principle of working as a team and being nik, a partner at Health Policy Strategies, Inc. “But the transparent.” data not disclosed would not have made a difference ◊ “We are in a trust industry and anything anyway. There’s a tremendous disconnect between re- that casts doubt about our [veracity] ality and perception. To some extent, it was the perfect damages us all.” storm brewing that bit Novartis.”

Another exec said Novartis was in a “no win situ- “Does this hurt Novartis? Of course, in the eyes of ation” and that while the CEO ultimately was the one public opinion,” says an industry expert who declines responsible, “there would have been multiple inputs to be identified. “Does this hurt Novartis in terms of and personalities chiming in along the way.” drug discovery and investment? Absolutely not.”

Asked if there was anything Novartis might have Vyondys 53 (golodirsen) for Duchenne muscular done differently, Slotnik points out that “Novartis is dystrophy, instead issuing a complete response letter not a small fly-by-night company.” It has experienced (CRL). The company had sought accelerated approval people who did what they did based on that experi- for the drug. ence, he tells AIS Health, and they obviously felt that “this was not information that necessarily needed to be disclosed. I’m going to give them the benefit of the “Does this hurt Novartis in terms of drug doubt.…This is not their first rodeo.” discovery and investment? Absolutely not.” According to Slotnik, “there’s a very interesting and careful balance” among what companies should disclose legally, regulatorily and “in the court of public Prior to the issuance of the CRL, analysts widely opinion. And that line constantly changes based on believed the agency would approve the drug, in part political and policy whims.” In addition to compa- based on the FDA’s approval of another Sarepta thera- nies’ understanding of what they do and don’t need to py for a different subset of people with Duchenne mus- disclose, they also must balance when and how they do cular dystrophy, Exondys 51 (eteplirsen), in September disclose that information. 2016. That drug’s approval process was a contentious one. During an April 2016 meeting, the FDA’s Periph- “This is classic Crisis Management 101,” he says. eral and Central Nervous System Drugs Advisory Com- “And God bless the FDA,” which is in “an impossible mittee voted against approval, questioning whether the situation of having to constantly balance” the intrica- small clinical trial sample size — 12 boys — was large cies of the industry. enough, among other things. The FDA requested additional information in June, and based on that, Janet “I’m going to give them the benefit of the Woodcock, M.D., director of the FDA’s Center for Drug doubt.…This is not their first rodeo.” Evaluation and Research, granted Exondys 51 accelerated approval. But her decision generated a great deal of pushback from colleagues within the agency, But the timing couldn’t be worse for the company including the filing of a formal dispute. FDA Commis- and the pharma industry, which has been under fire sioner Robert Califf, M.D., was forced to make the final over its drug pricing practices. decision, in which he deferred to Woodcock. Novartis recently said that Zolgensma has coverage Four days before the FDA issued the CRL for Vyon- plans from payers representing 40% of commercial dys 53, an Aug. 15 STAT article examined the status of lives, and high-profile news reports name Aetna Inc. Sarepta’s confirmatory trials for Exondys 51. The com- and Anthem, Inc. among insurers expanding their pany was required to conduct clinical trials confirming policies to cover more patients. So will the current the $300,000-per-year drug’s effectiveness, with a trial situation have any impact on pickup among payers and ending in 2020, followed by submission of data to the providers? FDA in 2021. But a plan for a trial that the company “I’m not on anyone’s P+T [i.e., pharmacy and submitted to the FDA in June said enrollment should therapeutics] committee, so I have limited insight into be started by the end of 2019 and gave an expected how Novartis actions impact coverage deliberations of date for results of 2024. those folks,” says Elan Rubinstein, Pharm.D., principal Per the article, “an FDA spokesperson told STAT at EB Rubinstein Associates. But based on the FDA’s that Sarepta is still being held to the 2020-2021 statement, “I expect there will be no more than a minor post-marketing requirement timeline established in and temporary blip in pickup of Zolgensma among the original Exondys accelerated approval agreement. providers and payers.” ‘FDA does not make a determination of whether a The second incident occurred Aug. 19, when the company has good cause for failure to comply with FDA declined to approve Sarepta Therapeutics, Inc.’s post-marketing requirement milestones until they are

actually missed,’ the FDA spokesperson said. ‘We can- among 90 drugs on the market that received accelerat- not stress enough the importance of the confirmatory ed approval between 1992 and 2008, 36% of required studies, both to the patients with Duchenne and their confirmatory studies were not completed by 2009 and families and to the community of patients who will half of those took an average of 5.5 years to begin. benefit in the future from accelerated approval.’” “Perhaps manufacturers do not feel a sense of Sarepta issued a press release following the FDA’s urgency to complete confirmatory studies, if the FDA rejection of Vyondys 53, saying that the CRL “gener- does not threaten to rescind pre-approval and if being ally cites two concerns: the risk of infections related on the U.S. market based on that pre-approval makes to intravenous infusion ports and renal toxicity seen full regular approval a moot point,” says Rubinstein. in pre-clinical models of golodirsen and observed “However, potential payer reluctance to cover a following administration of other antisense oligonu- product that does not have full regular FDA approval cleotides.” The company said it was “very surprised” should itself present sufficient rationale and urgency to get the CRL, as “over the entire course of its review, to complete a confirmatory trial.” As an example, he the Agency did not raise any issues suggesting the points to UnitedHealthcare’s policy on Exondys 51, non-approvability of golodirsen, including the issues which says the treatment is “not medically necessary that formed the basis of the complete response letter.” for treatment of Duchenne muscular dystrophy (DMD) It said it would work with the agency to resolve those due to lack of scientific evidence showing clinical bene- issues in order to gain the drug’s approval. fit and efficacy.” Asked if the FDA might pull Exondys 51 from the market if its confirmatory trials are behind schedule, “Data is data and speaks for itself.” Slotnik says, “no — I don’t see the FDA pulling it. But I think some payers may respond and will not cover An Aug. 19 STAT article said the FDA’s rejection it until the trials are done.” This action, he tells AIS “might represent a new and more restrictive regula- Health, “achieves the same goal without the FDA being tory policy at FDA, which could affect all companies involved. Regardless, though, this outcome would be developing drugs for rare diseases. But it might also bad for patients.” only pertain to Sarepta, which has had a contentious relationship with the agency for many years.…Sarepta’s “Potential payer reluctance to cover a delinquency on Exondys 51 may have angered the FDA product that does not have full regular enough to play a role in the agency’s decision Monday to reject Vyondys 53.” Analysts pointed to that earlier FDA approval should itself present approval as leading to FDA “payback,” saying the FDA sufficient rationale and urgency to was “slap[ping Sarepta] on the wrist for the prior ques- complete a confirmatory trial.” tionable accelerated approval of Exondys 51.” “One the one hand, you could view this as the FDA Slotnik points out that a number of publicly traded giving Sarepta payback,” says the unidentified industry companies have had FDA-related issues over the past 12 months that have posed a struggle for them. “Mind expert. “On the other, you want to believe that the FDA your Ps and Qs,” he says. “Nothing’s changed.” Drug- is not like this. They’re just humans doing their job.” At makers should “err on the side of caution and trans- the end of the day, “data is data and speaks for itself.” parency” and remember that “you get more bees with Last month, an article in the journal Manufac- honey.” turing & Service Operations Management, which is Contact Rubinstein at elan.b.rubinstein@gmail. published by INFORMS, an international association com and Slotnik at jayson@healthpolicystrategiesllc. for operations research and analytic professionals, com. G looked at accelerated approval. Researchers noted that the Government Accountability Office found that by Angela Maas

Reality Check: PCSK9 Inhibitors

Our Point of View

The two available PCSK9s, Praluent (alirocumab) from manufacturers Sanofi and Regeneron Pharma- ceuticals, Inc. and Repatha (evolocumab) from Amgen Inc., came onto the U.S. market in 2015 with list prices around $14,000 to $15,000 and quickly faced pushback from plans. Since then, the drugmakers have cut prices by more than 60%, but payers still have prior authorization on the drugs, including confirmation of an appropriate diagnosis and that members either have LDL cholesterol levels uncontrolled by statin medications or are intolerant to statins, says Mesfin Tegenu, R.Ph., president of Per- formRx. Patients also may be required to have a history of either established atherosclerotic cardiovascular disease or familial causes of hypercholesterolemia, says Erin Lopata, Pharm.D., senior director, access experience team at Precision for Value, and some plans may have additional requirements, such as a specialist prescriber, prior trial of Zetia (ezetimibe) and/or documented trial of lifestyle modifica- tions.

Coverage

Pharmacy Benefit Commercial Health Exchange Medicare More than 90% of the lives under the pharmacy benefit in commercial and health exchange formularies have utilization management restrictions on PCSK9 inhibitors. About 15% of Medicare beneficiaries are not covered for at least one of the products. Unrestricted Restricted Not Covered Not Listed

Medical Benefit

Under commercial and health exchange Commercial Health Exchange Medicare policies, almost 40% of the lives have utilization management restrictions. Under Medicare policies, more than 86% of the lives are not covered for at least one of the four products — Praluent Pen, Repatha Pushtronex, Repatha SureClick and Repatha Syringe — under the medical benefit. Covered Restricted Not Covered Unknown

DATA CURRENT AS OF Q1 2019

Reality Check: PCSK9 Inhibitors

AIS Health’s View

Some observers already call current PCSK9 pricing “value-based” since Amgen and Sanofi/Regeneron based the $5,850 yearly list price on value-based benchmarks established by the nonprofit Institute for Clinical and Economic Review. However, PCSK9s would be good candidates for true value-based payment arrangements since they “have a clear and measurable outcome in LDL reduction,” Tegenu says. Value-based contracts for PCSK9s could be developed to measure either long-term clinical outcomes — e.g., cardiovascular events — or short-term surrogate markers, such as LDL-C levels in patients treated with one of the products, says Lopata. She tells AIS Health that manufacturers and payers need to collaborate on the contracts to determine which outcomes measures they prefer and how the preferred outcome measures will be defined, tracked and paid for.

Trends From AIS Health

Drugmakers Slash Prices, Hope Plans See Value for PCSK9s Strategic Business, Financial and Regulatory Analysis of the Health Insurance Industry Health Plan Weekly

Amid Solid 1Q Results, Insurers Talk Up Deals, Partnerships May 7, 2018 As they reported first-quarter earnings over the past week, major health insur- VOLUME 28 | NUMBER 18 ance companies also took the opportunity to stress the value of partnerships and deals, assess the regulatory landscape, react to recent Medicaid contract awards and provide insight about whether they might re-enter some Affordable Care Act (ACA) Current Market Access to 3 Hypertension Medications exchange markets. During its May 3 quarterly earnings call, Cigna Corp. focused on its expecta- PCSK9 inhibitors, which fell flat in their debut four years ago as plans restricted access and Price, CareFirst CEO tion of consistent earnings growth following its yet-to-be-finalized $54 billion acqui- 4 Criticize Individual Mandate Repeal sition of pure-play PBM giant Express Scripts Holding Co. Cigna expects to finalize the deal, which was announced March 8, later in 2018 (HPW 3/12/18, p. 1). Aetna, WellCare Continue Brushing aside some investors’ concerns about bringing a PBM model into the 5 Favorable MCO Trend in 1Q mix, Cigna President and CEO David Cordani said that the combined company News Briefs will be better able to manage rising prescription drug and specialty pharmacy costs. 8 He said the proposed acquisition would result in a “deeper alignment” across the steered their members to older, cheaper anti-cholesterol drugs, may receive a second chance at health care delivery system, including pharmacists and drug manufacturers, while The AIS Report on allowing Cigna to provide integrated medical offerings and retain its marketplace Blue Cross and Blue Shield Plans flexibility. continued on p. 6 Blues Association, Plans 9 May Violate Antitrust Law, Ruling Finds Generics, Adherence Programs Can Ease Hypertension Costs 9 Blues Plans Address Recent guidelines that lower the threshold for hypertension treatment likely will Transportation, Hunger in raise costs by increasing the number of people receiving treatment, PBM executives improving their market share as manufacturers slash prices and promote a value proposition for ‘ZIP Code Effect’ say. But data show the wide range of generic medications available in the class could 12 Key Financial Data for moderate those cost increases. Leading Blues Plans In addition, it’s far better to treat people with hypertension than to leave their hypertension uncontrolled, given the risk for heart disease, stroke, kidney failure and other damage that is caused by uncontrolled hypertension, says Mesfin Tegenu, R.Ph., president of PerformRx LLC, a Philadelphia-based PBM that is a unit of the AmeriHealth Caritas Family of Companies. the biologics. “The most cost-effective use of anti-hypertensive medications is to ensure that members with high blood pressure are on the right medications and are adherent to the medication regimen,” Tegenu tells AIS Health. The generics first strategy is the main cost-saving measure in this class, but it’s critical to make sure that members Senior Reporters take the recommended medication, he says, adding, “there are little to no cost-sav- Judy Packer-Tursman [email protected] ing measures, outside of a generic first strategy, that would outweigh the benefit of Leslie Small members taking these medications when appropriate.” [email protected] Express Scripts’ 2017 Drug Trend Report, released in February, indicates that Executive Editor per-patient therapy costs are dropping in the high blood pressure/heart disease treat- Jill Brown ment category, and the lower per-patient cost more than offset the added cost to treat more people. The PBM said that commercial plan spending per member per Subscribers to AIS’s RADAR on Health Plan Weekly may read the in-depth article online Published by AIS Health, Washington, DC. An independent publication not affiliated with insurers, vendors, manufacturers or associations.

Express Scripts Inks Deal for Praluent Drug Benefits on Business Strategies and Analysis for Health Plans, Employers, PBMs and Pharma Companies

To Boost Medication Adherence, ‘Think Outside the Box’ Encouraging patients to take their medications as prescribed is a key priority for Subscribers to Radar on Drug health insurers, as nonadherence can fuel costly complications, hospitalizations and the Express Scripts national formulary. With the new deal, Praluent will be the preferred PCSK9 Benefits (formerly Drug Benefit News) can access searchable emergency room visits. To improve medication adherence, insurers are employing archives, back issues, postings tactics like reaching out when prescriptions aren’t refilled and offering mail-order from the editor and more services. But some are also thinking outside the box to overcome barriers that are at AISHealth.com. If you unique to their patient populations — namely, cultural and language barriers. need help logging in, email [email protected]. One of those insurers is Minnesota-based UCare, which serves members of the Hmong community in the Minneapolis/St. Paul metro area. The Hmong began on the formulary, and Amgen Inc.’s Repatha (evolocumab) will be excluded. coming to the state in 1975 to flee wars in their homelands in Laos, and today the Twin Cities are home to the largest concentration of Hmong in the United States, Senior Reporters Judy Packer-Tursman according to the Minnesota Historical Society. [email protected] Of the more than 12,300 members in UCare’s Minnesota Senior Health Op- Leslie Small tions (MSHO) dual-eligible plan for members 65 and older, about 18% are of Asian [email protected] descent, Director of Pharmacy Patrick Mitsch, Pharm.D., tells AIS Health. And Executive Editor Jill Brown among them, about 1,200 speak Hmong as their primary language. Director, Data Solutions “Some of the things that we encounter with engaging with our Hmong com- Susan Namovicz-Peat munity is our traditional methods of communicating with them don’t work for whatever reason,” Mitsch says. “Whether it’s a print letter that we send out to give Subscribers to AIS’s RADAR on Drug Benefits may read the in-depth article online Published by AIS Health, Washington, DC. An independent publication not affiliated with insurers, vendors, manufacturers or associations.

Researcher: Discounts May Work as Well As Some Outcomes-based

Contracts Drug Benefits on Business Strategies and Analysis for Health Plans, Employers, PBMs and Pharma Companies

Express Scripts Inks Deal to Improve Praluent Price, Access May 25, 2018 Express Scripts Holding Co. has struck a deal with the manufacturers of Pralu- VOLUME 19 | NUMBER 10 ent (alirocumab), one of two pricey PCSK9 inhibitors on the market, that will give the PBM a lower net price on the drug in exchange for streamlined patient access and an exclusive spot on the Express Scripts national formulary. 3 Express Scripts Initially Resisted Cigna’s The agreement significantly simplifies the documentation necessary to secure As outcomes-based contracting gains ground, a University of Pittsburgh School of Pharmacy Overtures, Filing Shows insurance coverage, and may help reduce out-of-pocket costs for eligible patients, according to Praluent manufacturers Regeneron Pharmaceuticals Inc. and Sanofi. 4 Trump’s Near-Term Rx The pact, unveiled May 1, comes after Regeneron and Sanofi announced in Proposals May Not Hurt March that they would lower the net price of Praluent for payers willing to reduce PBMs, Insurers access barriers for appropriate patients. This is the first such agreement, but analysts predict additional similar deals to come, and one warns that payer costs could rise as 7 Infographic: Current a result. researcher asserts it may be no more cost effective than existing industry discounts. She urges Market Access to PCSK9 “This is where the formulary strategy may ultimately generate cost increases for Inhibitors some payers,” says Joshua Golden, area senior vice president at Solid Benefit Guid- ance, a division of Arthur J. Gallagher & Co. “Personally, I’m concerned that any News Briefs 8 financial gains on pricing may be eroded by increased utilization. We’re encouraging our plan sponsor clients to pay close attention to PA [i.e., prior authorization] approval and denial rates over the coming year for this class of drugs.” payers to be cautious about how they form such agreements with pharmaceutical manufacturers, continued on p. 5 To Boost Medication Adherence, ‘Think Outside the Box’ Encouraging patients to take their medications as prescribed is a key priority for Subscribers to Radar on Drug health insurers, as nonadherence can fuel costly complications, hospitalizations and Benefits (formerly Drug Benefit News) can access searchable emergency room visits. To improve medication adherence, insurers are employing archives, back issues, postings tactics like reaching out when prescriptions aren’t refilled and offering mail-order describing what she sees as “clearly a marketing move” by Amgen Inc. over its cholesterol-lowering from the editor and more services. But some are also thinking outside the box to overcome barriers that are at AISHealth.com. If you unique to their patient populations — namely, cultural and language barriers. need help logging in, email [email protected]. One of those insurers is Minnesota-based UCare, which serves members of the Hmong community in the Minneapolis/St. Paul metro area. The Hmong began coming to the state in 1975 to flee wars in their homelands in Laos, and today the Twin Cities are home to the largest concentration of Hmong in the United States, Senior Reporters Judy Packer-Tursman according to the Minnesota Historical Society. drug Repatha (evolocumab). Yet Harvard Pilgrim Health Care, Inc., Cigna Corp. and other payers [email protected] Of the more than 12,300 members in UCare’s Minnesota Senior Health Op- Leslie Small tions (MSHO) dual-eligible plan for members 65 and older, about 18% are of Asian [email protected] descent, Director of Pharmacy Patrick Mitsch, Pharm.D., tells AIS Health. And Executive Editor Jill Brown among them, about 1,200 speak Hmong as their primary language. Director, Data Solutions “Some of the things that we encounter with engaging with our Hmong com- Susan Namovicz-Peat munity is our traditional methods of communicating with them don’t work for swear by their outcomes-based agreements with Amgen for this drug as a win for all. whatever reason,” Mitsch says. “Whether it’s a print letter that we send out to give Published by AIS Health, Washington, DC. An independent publication not affiliated with insurers, vendors, manufacturers or associations. Subscribers to AIS’s RADAR on Drug Benefits may read the in-depth article online

Reality Check: PCSK9 Inhibitors Key Findings

Characteristics Contracting Competition In May 2018, Sanofi and Regeneron lowered the annual cost of Indications Praluent from $14,600 to between $4,500 and $8,000. In January 2019, Amgen announced that all Repatha device options’ prices had been reduced by 60%, from $14,000 to $5,850 per year. Hypercholes- terolemia Pharmacy and Medical Benefit Implications Coverage is highly restricted with multiple steps and a laundry list of Step-Therapy (ST) Policies prior-authorization restrictions. All products are covered under the pharmacy benefit, but some also have medical coverage, which is A review of ST policies for rarely used by health care providers or the pharma companies. payer-controlled formularies:

No ST (8%) ST AIS Health’s View (92%) Pfizer Inc. discontinued the development of its PCSK9 bococizumab in 2016, claiming that Single Step the product was “not likely to provide value to (34%) patients, physicians, or shareholders.” But the Multi Step Medicines Company’s inclisiran is in Phase III (66%) trials, and in August the manufacturer said that one trial showed positive results for twice-yearly dosing of the product to decrease LDL cho- Prior-Authorization (PA) lesterol. The company says it expects to file for Policies FDA approval by the end of 2019. Lopata calls inclisiran “a promising pipeline product with a A review of PA policies for different approach to PCSK9 inhibition and the payer-controlled formularies: potential for a more convenient dosing regi- No PA men.” However, she notes that clinical data is (9%) still being developed. “Payers will be expecting strong clinical value — including cardiovascular PA (91%) outcomes data — as well as competitive pricing compared with the other PCSK9s for formulary Appropriate consideration once approved,” she says. (36%) Restrictive (64%) DATA CURRENT AS OF Q1 2019

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