World Vision 360˚
JULY 2020
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The Bigger Picture Exploring Latin China Turns COVID-19 Regulatory Four Digital Saviors And Global America In The Crisis Into A Global Harmonization Makes Of Indian Pharma Innovation Hotspots COVID-19 Era Health Care Opportunity Big Strides In Africa During COVID-19 WORLD VISION 360˚
Contents
The Bigger Picture And Global Innovation Hotspots 3
Exploring Latin America In The COVID-19 Era 8
China Turns COVID-19 Crisis Into A Global Health Care Opportunity 14
Regulatory Harmonization Makes Big Strides In Africa 18
Four Digital Saviors Of Indian Pharma During COVID-19 23
July 2020 | In Vivo | 2 WORLD VISION 360˚ The Bigger Picture And Global Innovation Hotspots
BY DANIEL CHANCELLOR ore than ever, the biopharmaceutical industry is a global affair. The lure of the US is undoubtedly huge, accounting for approximately 40% of total prescription revenues, thanks in Executive Summary part to an incredible 18% of its gross domestic product (GDP) Focusing too much on the US spent on health care. As such, dynamics within the largest provides a blinkered view of the Mmarket can often have far-reaching consequences, such as directing portfolio industry and prevents access to strategy for multinational companies and influencing the timing and size of the myriad opportunities on offer financing and acquisition decisions. However, focusing too much on the US globally. provides a blinkered view of the industry and prevents access to the myriad opportunities on offer globally. In Vivo explores some of the innovation hotspots in the rest of the world and how these are poised to shape the global picture in the years to come.
Gene Therapy Development In China After three decades of fine-tuning, gene therapies are now finally emerging as potential curative treatment options across a range of therapeutic areas and high unmet need diseases. Expanding the definition to include cellular or viral therapies that have been genetically modified ex vivo, there are currently 12 gene therapies approved anywhere in the world, while a further three have been withdrawn from the market. The first classic therapy delivering a healthy copy of a gene directly into a patient, Novartis AG’s Luxturna (voretigene neparvovec), was approved in 2017 and a whole host of therapies are set to follow.
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There are large number of obstacles facing this novel taking on the mantle. Two companies in particular, treatment modality as it matures, not least the scientific Hrain Biotechnology and Hebei Senlang Biotechnology, validation across different diseases, but also regulatory, have the largest pipeline of internally discovered gene commercial, manufacturing and logistical hurdles to therapies of any company globally, according to data overcome. As expected, the US biotech sector is a from Pharmaprojects (see Exhibit 1), which tracks drug leading contributor to the early development work of development all the way from preclinical assets to gene therapies, rising to meet these challenges, but widely launched brands. entrepreneurial Chinese biotechs are increasingly
Exhibit 1. Leading Originators Within Cell And Gene Therapy Pipeline
Company Originator drugs Licensed drugs Hrain Biotechnology 20 n/a Hebei Senlang Biotechnology 19 n/a Editas 16 n/a Sangamo Therapeutics 16 2 Regenxbio 15 7 Precigen 13 1 Shanghai Unicar-Therapy Bio- 13 n/a medicine Technology Amicus Therapeutics 12 n/a Autolus 12 n/a Genethon 12 3
Pharmaprojects, March 2020
China is also a leading location of clinical trials for As shown in Exhibit 2 , China is the global leader in gene therapies, demonstrating that it is equipped to ongoing academic gene therapy clinical trials, and is manufacture these products on scale, while demand a close second to the US for all sponsor types. As of for supply of viral vectors among Western CDMOs can spring 2020, there were 503 ongoing gene therapy act as a bottleneck, with various reports suggesting a trials in the US, compared to 451 in China, although an waitlist of up to two years. Part of the success story is impressive 90% of these Chinese trials are sponsored the intense involvement of academic centres in China, either by academia alone or in collaboration with providing much-needed investment into the gene another organization. The corresponding proportion therapy space, compensating for the weaker early-stage in the US is 60%, while academic involvement in trials fundraising environment. operating in European countries falls to a lowly 20-30%.
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Exhibit 2. Top 10 Locations With Ongoing Gene Therapy Trials By Sponsor Type
United States China United Kingdom France Germany Italy Spain Canada Japan Belgium 0 100 200 300 400 500 600
Number of Trials
Industry Academia Government Collaborative
Source: Trialtrove, March 2020
Gene therapy has undoubted clinical potential, and the top five countries globally for biotech, with its with an abundance of research coming out of Chinese lofty position in the Scientific American Worldview laboratories, the next question is whether domestic scoring driven by its productivity, quality of workforce biotech companies will be equipped to lead on and government policy. Nevertheless, Australia lags commercialization. Thus far, few Chinese-originated somewhat behind its peers on financial measures drugs are available in US and European markets, such as prescription drug expenditure (14th largest and the early model for advanced therapies is one market globally), while recent fundraising activity across of partnership. One recent example is the licensing financing and partnership deals is dwarfed by the totals agreement between Legend Biotech and Johnson & achieved by companies in South Korea, Canada, and Johnson for the CAR-T drug LCAR-B38M, commanding a smaller European countries such as the Netherlands healthy $350m upfront payment. While BeiGene Ltd., a and Belgium. flag bearer for Chinese R&D innovation, succumbed to the lure of an established commercial entity, selling a However, one area in which Australia punches above its 20.5% equity stake to Amgen Inc. for $2.7bn in October weight and can rightly claim to be globally competitive 2019. Based on the current dynamic, Chinese biotech is in clinical trials, and especially with early-stage is certainly well positioned in the engine room for gene development. therapy discovery but is unlikely to break through as global commercial enterprises, providing big pharma Multinationals are increasingly attracted to Australia multinationals with ample business development to perform clinical research not only as part of global opportunities. registration programs, but also to conduct single location Phase I studies. As shown in Exhibit 3 , clinical Early Clinical Trials In Australia trial growth in Australia over the last decade has On the global scale, Australia sits in a relatively outpaced that of the wider industry. Collectively, the modest position on a variety of metrics considering biopharma industry initiated just shy of 60,000 trials its population of approximately 25 million people over 2010-2019, 7% of which (4,383 trials) included at and excellent health care coverage, provided by the least one study location in Australia. Excluding the slight Pharmaceutical Benefits Scheme (PBS). The industry blip in 2019 – there is commonly a lag in reporting full body AusBiotech proudly touts Australia as among study locations for new clinical trials – the number of
July 2020 | In Vivo | 5 WORLD VISION 360˚ trials in Australia grew at a compound annual growth country globally for Phase I and I/II studies initiated in rate of 4.4%, exceeding the 2.7% global figure in the the last year, behind only China, the US and the UK. period to 2018. Overall, this is enough to place Australia It is certainly a powerhouse for pharmacokinetic and in 12th position globally for the number of industry- safety studies, where the Clinical Trial Notification (CTN) sponsored trials over the whole decade, rising to 10th scheme enables a company to get approval for a trial in when looking at new starts in 2019 alone. as little as six weeks, contrasting INDs in the US taking, The statistics are even more favorable for early-stage potentially, up to a year. research: Australia ranks as the fourth most common
Exhibit 3. Growth In Industry-Sponsored Clinical Trials In Australia
700
600 528 479 503 500 426 426 447 444 374 371 385 400
300
Number of Trials 200
100
0 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019
Global (x10) Australia
Source: Trialtrove, March 2020
Finances also play a hugely important role for the challenges. Once fully operational, the fund will attractiveness of performing clinical research in support an additional AUD$650m annual investment. Australia. The government is notoriously supportive of Although smaller, the government has also set up business. It invests heavily to support the biopharma the AUD$500m biomedical translation fund, which industry both directly via research funding and provides companies with venture capital to develop indirectly via tax rebates. Australia’s competitive R&D and commercialize biomedical discoveries in Australia, tax incentive scheme provides companies with a boosting the domestic industry with the stipulation that refundable tax credit in the region of 38.5-43.5% for the investment stays within Australia. research conducted in Australia, with eligibility recently raised up to an expenditure cap of AUD$150m ($105m). AI-Enabled Drug Discovery In The UK This is one of the factors why like-for-like clinical The past year has been notable in the number of research can be notably cheaper in Australia than many alliances signed between large biopharma companies other developed countries. and specialists operating in the artificial intelligence (AI)-enabled drug discovery niche. Furthermore, in May The federal government also invests around AUD$850m 2019 the influential Tufts Center for the Study of Drug annually in health research via the National Health and Development reported results from its own industry Medical Research Council (NHMRC), and separately survey, with 59% of respondents planning to expand established the AUD$20bn Medical Research Future AI staff through 2020, suggesting its widespread and Fund (MRFF) in 2015. This fund has already enabled growing uptake across drug development. (Also see the creation of eight large scale public health missions “PharmAI – Industry Is Smartening Up To Potential Of since 2017, spanning a wide range of health care Artificial Intelligence” - In Vivo, 3 Jun, 2019.)
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The fundamental driver behind this is to improve R&D separately raising $269m across three funding rounds productivity, bringing rationally designed medicines since 2014. As the company progresses, it continues to with scientifically validated mechanisms into the most evolve its knowledge graph, a vast network of distinct appropriate patients, all in a shorter space of time and data sources aiming to yield a better understanding of with a greater probability of technical success. Pure biological complexity. This can then be used to implicate computational power and iterative machine learning known targets in potentially new indications, optimizing (ML) processes enables these algorithms to process an drug design against these and eventually enrolling incomparably greater amount of data to the human the most likely patients to respond into clinical trials. brain, which when allied to our current understanding Its internal amyotrophic lateral sclerosis (ALS) drug of disease and scientific intuition, produces highly discovery program is borne out of a target previously optimized drug discovery programs. The field is studied in breast cancer, while its platform has even certainly nascent, but is taking off rapidly with been used to propose the repurposing of JAK inhibitor investor support and numerous lucrative partnership baricitinib as an adjunct to antivirals in the treatment of arrangements between pharma and AI pioneers, COVID-19. Demonstrating the breadth of its capabilities, several of which are based in the ‘Golden Triangle’ BenevolentAI’s commercial relationships are targeted of the UK; Cambridge, Oxford and London. Two against oncology, chronic kidney disease, and idiopathic companies in particular, Exscientia and BenevolentAI, pulmonary fibrosis. are among the frontrunners in terms of clinical milestones and high-profile alliances. AI-ML certainly has its limitations and, like many new technologies, falls victim to being over-hyped. Organic Exscientia Ltd., headquartered in Oxford and with chemist and renowned industry blogger Derek Lowe offices in Dundee and Osaka, claimed in January 2020 is rather scathing in his assessment of the novelty that to have become the first AI company to discover a the Sumitomo Dainippon/Exscientia drug offers. “This drug that has progressed into human clinical trials. Its project, at best, seems to me to have shaved a few collaboration with Sumitomo Dainippon Pharma Co. months off the process of sending their compound into Ltd. yielded a drug candidate for obsessive-compulsive the same black-box shredder as every such drug project disorder, reaching the point of entering clinical trials goes into when it hits human trials.” The key limitation within 12 months of program inception, in contrast to of AI-ML algorithms is that they do not advance our several years of preclinical work based on standard collective scientific understanding by themselves, timelines. Previously, Exscientia delivered its first lead and do not circumvent the key destruction of value in molecule to GlaxoSmithKline plc in a COPD-focused R&D – failure of proof-of-concept efficacy trials. As a research program, reaching this milestone after testing 5-HT1a agonist, the Sumitomo Dainippon/Exscientia just 85 compounds across five development cycles, drug DSP-1181 is not at all unique pharmacologically prompting chief research officer Andy Bell to effuse and binds a target that is not definitively linked with about his company’s industry-leading AI discovery the disease state. Nevertheless, this is a single example platform. (Also see “The Drug Hunter’s Assistant: and over the coming years, multiple case studies will Accelerating Drug Discovery With AI” - In Vivo, 25 Nov, help to reconcile its technological promise with clinical 2019.) The company also has ongoing collaborations reality. Eventually, many processes within AI-enabled with five other large pharmaceutical companies, while drug discovery will become embedded in biopharma progressing various co-development and internal best practices, with data science expertise becoming a programs centred on oncology, immunology and core capability rather than a buzzword. It would not be fibrosis. a surprise should a big pharma company move in this direction via an acquisition, especially if the AI specialist BenevolentAI may have been beaten to these key itself generates an attractive internal pipeline. milestones by its near neighbour, but it is also working to advance the use of AI across the whole drug Until this point, it will be the role of specialist companies development progress. The company holds a London such as Exscientia and BenevolentAI to continue to headquarters and maintains proximity to Cambridge via validate the technology and achieve the next key a research facility. Last year, BenevolentAI announced milestone of producing the first AI-designed drug to collaborations with both Novartis and AstraZeneca PLC, gain regulatory approval.
July 2020 | In Vivo | 7 WORLD VISION 360˚ Exploring Latin America In The COVID-19 Era
BY BEN COMER - Specialty drugs and biologics often are not covered by public health systems in Latin America, a region comprised of 20 countries and 640 million people. Amgen Inc. is using its biosimilar portfolio to create a footprint in new Latin Executive Summary American markets. Unique industry partnerships and new regulatory flexibility in Latin - COVID-19 is instigating regulatory flexibility in Latin America; health America may help to improve authorities have adopted electronic submissions and other online tools. access to medicines, even as Brazil, Argentina, Colombia and Peru have published guidance for remote COVID-19 wreaks havoc in the patient monitoring in clinical trials. region’s largest pharmaceutical market. Can biopharma’s bespoke solutions to market - Patients with chronic and rare diseases have faced interruptions in access, access barriers coalesce into a as health systems prioritize patients with COVID-19. In some countries, strategy capable of overcoming patients can’t get access to a stable internet connection, even where political, economic and COVID-19 telemedicine and other virtual services are offered. related risks? At the BIO 2020 conference in June, which was held virtually due to the COVID-19 pandemic, speakers on a panel about the impact of coronavirus on health care delivery worried aloud about a coming reduction of public funds for medicines in the US and Europe. An economic recession, speakers feared, could lead to reductions in drug coverage and cost containment measures in the world’s largest markets. To prevent a tightening in market access, the biopharma industry will have to “find innovative solutions ourselves and collaborate with health systems and policy makers to enact them,” said Stefan Neudoerfer, senior director, head of market access Europe, CSL Behring.
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This strategy – of creating solutions in collaboration with an increase in specialty drugs and rare disease with key stakeholders in individual markets – is already products. In Brazil, the private insurance market, which playing out in Latin America, where public funds for is primarily offered through employer plans, covers innovative medicines have always been a challenge to roughly 25% of the population, with public health care secure, and where private insurers, which cover a much funds covering the remaining 75% of the population, smaller slice of the population compared with the US or says Elvin Penn, general manager, Amgen Brazil. Europe, are pushing back against rising costs associated
“With the COVID-19 situation, there is more pressure on the [Brazilian] government in terms of budgets and resources available to treat patients.”
Elvin Penn, General Manager, Amgen Brazil
In Mexico, where Penn was previously Amgen’s general fastest growth regions,” said Ian Thompson, Amgen’s manager, only around 6% of the population is covered SVP and intercontinental general manager. “But it by private insurance. In both countries, “the public also comes with some volatility.” The combination of system is always more restrictive, has less availability of growth potential and challenging access conditions resources, and a lot more demand because most of the has led to the development of innovative solutions population depends on the public system,” said Penn. for patients in the region. “Some of our best ideas, “And the level of funds changes, because it depends on some of our brightest young talents, and some of the economic situation, and in some cases it depends our most interesting collaborations are coming on administration in power at a given moment,” said out of Latin America,” said Thompson. “Ideas and Penn. “With the COVID-19 situation, there is more platforms and initiatives that began in Latin America pressure on the government in terms of budgets and are now becoming standards of excellence across the resources available to treat patents.” business.” Thompson cited a patient support platform in Colombia that manages patient information, privacy For Amgen, one of the world’s largest biologics and compliance requirements, which is now being companies, Latin America –a region with a population of replicated in other parts of the world. 640 million people across 20 countries – is “one of our
“Ideas and platforms and initiatives that began in Latin America are now becoming standards of excellence across the business.”
Ian Thompson, SVP, Intercontinental General Manager, Amgen
Amgen is also leveraging its biosimilars portfolio as countries. In 2019, Amgen Brazil entered into a formal a tool for market access in Latin America and has 15 Productive Development Partnership (PDP) with Libbs different biosimilar products approved across several Farmacêutica, a private Brazilian company, and the
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Instituto Butantan, a public research institute, which Like other companies, Amgen has dramatically reduced will create the first local manufacturing capacity for face-to-face contact with physicians. “Net-net, we are Amgevita, a biosimilar version of AbbVie’s Humira still down in the number of interactions we’ve had, (adalimumab). The 10-year agreement will allow Amgen which does have an impact on some products, but to make imported supplies of Amgevita available to our teams have been very resourceful and customer- patients immediately, with a transition plan to transfer focused in adjusting their communications to provide the technology into Brazil when the local manufacturing information services, particularly COVID-19 related infrastructure comes online, Penn says. The cost of services to customers that make inquiries about it,” said adalimumab and other biologics account for over half Thompson. “We’ve been very pleasantly surprised by of the Brazilian Ministry of Health’s annual drug budget, our ability to bring large audiences into virtual congress and biosimilars are a strategic priority. The PDP is seminar type activities. We have attracted higher Amgen’s first partnership of this kind in Latin America. numbers of customers to an event - say for example in “We’re very excited about it, because it will give us Mexico City - then you’d be able to get live, because of the opportunity of make [Amgevita] available for the traffic restrictions and congestion restrictions. We’ve patients in the public system,” he said. had meetings where we’ve had over 1,200 people attend and participate fully and engage really well, Biosimilars are helping to create a pathway into new and that’s been very effective.” Amgen has also run markets in Latin America, especially when paired with advisory boards and large-scale launches – Thompson value-based partnerships, notes Thompson. “We’re able said the company had successfully launched “a couple to enter some Latin American markets quickly post loss of products virtually” – which is important, since “it’s of exclusivity because of the affordability component going to be part of the new normal.” However, some … it’s a way to establish a footprint in some of these markets in Latin America are more equipped for digital markets. Biosimilars drive competition, and competition engagement and multi-channel marketing than others, creates more affordable options,” he said. said Thompson.
Amgen is involved in 44 “innovative contracts” across Protecting patients’ continuity of care is another the Latin American region, including in Brazil, Mexico, chief concern during the pandemic; unusual times Colombia and Argentina, with a variety of payers, says call for unusual measures. In Brazil, the frequency of Thompson, who described the partnerships as requiring commercial flights has dropped precipitously, which both parties to put some skin in the game. “The nature has affected the availability of flights for Amgen’s of our value-based partnerships requires rigorous drug distribution. The solution? “We have been using compliance and legal/regulatory sign-off, so it’s a slightly other channels for distribution, specifically charter different pathway compared with a standard discount flights, so that our patients continue receiving our or volume-based approach,” said Thompson. “They drugs with no interruption,” said Penn. “That has are bringing value and we do see them reducing costs, required some additional effort from our supply chain improving care, and enhancing the patient experience.” team, but our patients have continued to receive the Thompson highlights that the contracts are active in drugs as well as the service levels we offered before multiple markets, touching roughly 40,000 patients the crisis.” Chartered flights for drug distribution and 16,000 health care practitioners, and including may not be a sustainable long-term strategy but cardiovascular and oncology products, among others. figuring out how to send medications to patients’ homes, a common practice in many mature markets, The key to setting up innovative contracts, says becomes critical during a pandemic. “Hospitals have Thompson, is tailoring them to the needs of the been a key component of COVID-19 transmission, so individual institution or stakeholder. “Our cross- sending medicines to patients’ homes when suitable, functional team will seek to understand the challenge as opposed to putting patients and nurses at risk of [a stakeholder] is trying to overcome, how can we contagion, should be an important lesson learned,” said ensure patients that need this product can get it, when Thompson. “I think there is potential for the industry they need it. Stakeholders sit down together and work to help rebuild a more resilient health care ecosystem, out very often a unique pathway,” he said. “In some and partner with health care ecosystems, to ensure situations, it might be a rebate or a concession at the this resilience is built in so that it is perhaps less easily end of the year, but it might be something completely penetrated by something like Covid-19 in the future.” different, it could focus on services or education. What would be a great outcome for the institution, for the Regulations In Flux insurance company, for patients, and how can we make Health authorities in Latin American countries, in the that work together?” past, have not been known for their speed of regulatory action. Prior to the pandemic, regulators in many
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Latin American countries required the submission of Horta Gomes noted that the most common change paper documents and ink signatures. Additionally, the among regulatory bodies across the region was the interpretation and roll out by global regulators of an adoption or increased use of online tools, email and international Identification of Medicinal Products (IMDP) electronic platforms, both for the submission of has not happened yet. “We really want to see regulators documents, and for conducting virtual meetings with come together on this,” said Ronan Brown, SVP, head of applicants. Other changes per Horta Gomes, some IQVIA integrated global compliance. formal and some informal, include: Before the biopharma industry switched its focus - Honduras and El Salvador are now allowing digital to specialty and rare disease treatments, Argentina submissions during the pandemic. and Brazil were critical markets for conducting large - Peru and Uruguay are handling pharmacovigilance hypertension or diabetes clinical trials, said Brown. reports online exclusively. “But they would take 12 to 18 months to come online, - Colombia and Chile formally waived requirements for so unless your recruitment period was two years, wet signatures. at minimum, you’d really struggle to include Latin - Regulators in Brazil and Colombia (Anvisa and Invima, American countries,” he said. With smaller trials for rare respectively) adopted the Pharmaceutical Inspection diseases, Latin America has been left behind, due to the Commission (PIC/S) GMP reliance initiative, as well decrease in clinical sample sizes needed, and costs of as mutual recognition of foreign manufacturing work for running those studies. inspections from member countries. - Brazil’s Anvisa formally introduced a resolution A potential silver lining of the COVID-19 pandemic can allowing the possibility of remote inspections, or be seen in recent actions taken by regulatory authorities inspections by video conference. in Latin America. Cammilla Horta Gomes, Latin America - Argentina joined the WHO’s COVID-19 Solidarity regulatory policy lead at Roche, Brazil, detailed Clinical Trial. numerous regulatory changes and flexibilities across - Brazil, Argentina, Colombia and Peru published Latin America in a recent webcast with Alberto Grignolo, guidelines for patient remote monitoring in clinical editor-in-chief, DIA global forum and corporate vice trials. president at Parexel. “In Latin America, some authorities - Costa Rica began granting extensions for marketing are adopting very interesting approaches to come authorizations. up with alternatives to the challenges they’re facing,” - Argentina, Bolivia, Brazil, Colombia, Peru and other said Horta Gomes. “Regulators want the continuity of countries are prioritizing assessment and approval of R&D but at the same time they may have to deal with COVID-19 related products. a sudden surge of new clinical protocols because of pandemic. They must ensure a minimum normality in Horta Gomes believes the three most important areas their regulatory processes, but also deal with urgent for regulatory action in Latin America include GMP demand for applications, and they have deal with certifications, and establishing reliance or recognition doing it from home. They also have to maintain access mechanisms, such as certificates issued by PIC/S to products when global supply chains are complete members; reliance schemes for the registration of new disorganized.” products approved in mature markets like the US and
From Patients To Policy Advocates The Latin American Patients Academy (LAPA) is a non-profit group aimed at “building and facilitating strategic alliances between civil society leaders and public health decision makers in Latin America.” On a panel with other patient advocates during the BIO 2020 conference, Eva María Ruiz de Castilla, LAPA’s founder and director, said the COVID-19 pandemic had been difficult for patients in Latin America, many of whom were struggling with a good enough internet connection to speak with a physician, despite a rapid expansion in available telemedicine services. But the organization has had some successes, such as in Colombia, where patients organized a recurring meeting with government officials, every 15 days, for updates on the current situation and to learn how patients can help.
Access to medicines was a LAPA priority, said Ruiz de Castilla, since hospitals and other health care facilities have largely transformed into COVID-19 centers for care. “Chronic and rare disease patients aren’t able to get access to the same services as in the past.” Transportation was an issue, and LAPA has been working to get ambulances to bring patients in for infusions, Ruiz de Castilla said. In Brazil, ride-share services such as Uber
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and Cabify have entered into collaborations with hospitals and other facilities in order to safely deliver patients for treatment, such as chemotherapy. As physicians and health care systems in Latin America shifted to caring for COVID-19 patients, they had forgot about other diseases beyond COVID-19, she said.
On clinical trials, one of LAPA’s objectives is to bring Latin America’s regulators in line with other geographies, to match the speed with which other regulators make decisions. “To us it’s very important to get access to clinical trials, it’s an opportunity for patients, and a learning opportunity for physicians and researchers, so we are advocating for more access to trials.” The challenge, said Ruiz de Castilla, is that “information about clinical trials is limited, and when we get the information, it’s too late for us to help patients access the trials. We need to help the system go faster, and we need to get the right information at the right time.” (Also see “Expanding The Tent: Improving Trial Participation Among Under-Represented Patient Populations” - In Vivo, 8 Apr, 2020.)
Stronger, broader collaboration is at the top of Ruiz de Castilla’s wish list. She said, “The pandemic is showing us great examples of global, and local, collaborations, ways of working in which patients are at the center or are at least involved. New ways of working in partnership are being discovered, and we are all working toward the same objectives,” she said. “If we don’t collaborate, everything will take longer.”
Europe; and post-approval changes for repurposed in emerging markets recognized “this big juggernaut products, which may be already authorized for use coming along” in the form of expensive specialty in other countries, but are now being repurposed for therapies and biologics. “That was not sustainable to the prevention or treatment of COVID-19. “Reliance the public purse … the public sector [in many emerging for this post-approval scenario might even be more markets] only looks at a fraction of the disease important than reliance pathways for new products,” populations.” In sickle cell disease, for example, Masters she said. “Reliance,” which denotes the total acceptance said “our studies in northeast Brazil showed us that the of another regulator’s decision, is different from recommended treatment for the population should be recognition, which is a regulator’s decision to accept a 30% coverage of the product. And yet, Brazil can only specific regulator’s decision, or part of a decision. afford 8.33% of coverage.”
Building A Market For cash-strapped public insurance systems, Masters Given the challenge with public health funding and conducts health care technology assessment modeling resources in many Latin American countries, companies to determine how a partner company might offer may choose not to go to the trouble of registering an tiered pricing, as a way in. The company also works innovative product in Bolivia, for example. But specialty with patient advocacy organizations, charities and and rare disease products are urgently needed in foundations, as well as large government buying many emerging markets, since “those patients are no organizations or group purchasing organizations, to different from patients in California, London or Paris,” understand unmet need in a particular market. “We go said Zulf Masters, CEO of Masters Specialty Pharma, to the health authorities or the ministries and look at a private pharmaceutical and distribution company their repositories and data, and mine that data for need focused on emerging markets. Masters specializes in assessment,” said Masters. local knowledge of emerging markets, including Latin America, and operates in 75 countries. When reached Since many orphan diseases have a genetic component, for an interview with In Vivo, Masters was in the process genetic testing will increasingly become the first of sourcing 5 million rapid COVID-19 tests for Brazil, a step to establishing a new market. “That’s the first task he described as “a rapidly moving target.” thing you build: you put the lab in, put the tests in, encourage testing, and then with testing you have a Masters’ business model involves partnering with patient population that’s eligible for your product,” said biopharmaceutical companies to either distribute Masters. “That is exactly what Genzyme and Shire have their products in emerging markets under an exclusive done.” distribution deal, or by working with local health authorities to secure expanded access for patients. Masters is not involved in genetic screening but said For companies focused primarily on mature markets, the company was “talking to small, innovative biotech Masters helps to grease the wheels in emerging companies in Cambridge, Massachusetts, who have markets, in terms of regulatory clearance and sales and drugs on the horizon that will require setting up local marketing. Years ago, said Masters, health authorities testing and local labs.”
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Masters founded the company 35 years ago, after the implementation of electronic labeling,” said Roche’s working as a rep in the Caribbean for the Beecham Horta Gomes. Group, and noticing that poor countries, like Haiti, “were completely forgotten by the first world nations and In interviews with In Vivo, Penn and Thompson at the major pharmaceutical companies.” He said local Amgen said it was too soon to discuss COVID-19 knowledge and a relationship with regulatory groups distribution strategies for Latin America. There are are the most important lubricants for market access over 500 product candidates currently being tested in emerging markets. “A lot of people will tell you that against COVID-19; many will not make it to the [Brazilian regulator] Anvisa is very challenging … you finish line. Infectious disease vaccines are not a high mention Anvisa and say, ‘I don’t want to go there.’ But margin product category for the biopharmaceutical we’ve made it our mission over the years to learn and industry, but it is heartening to see the level of global work with these health authorities, and to find out collaboration, and participation, from the industry. “We exactly what they want,” said Masters. “At the end of have an opportunity, an obligation, a responsibility, to the day, there’s a reason behind what they want. If you work as hard as we can and as collaboratively as we can can understand that and interpret it correctly, it’s not a to bring potential solutions to market,” said Thompson. problem.” Interestingly, it is not the emerging markets “It’s quite risky. Once solutions are found, making those that represent the challenge, it’s getting the drugs from treatments available and not restricting them because large pharmaceutical companies, and ironing out an of geography or cost or price, will also be important.” agreement – especially for specialty and rare disease products,” he said. “I think it’s shown what is possible when people put their minds together with respect to removing barriers,” COVID-19 As Opportunity said IQVIA’s Brown. “What we’re seeing in the last three Brazil in particular has fared poorly in the pandemic, months has been that the regulators have moved and the situation is not improving. COVID-19 modeling heaven and earth to accelerate potential treatments. I from The Institute for Health Metrics and Evaluation would love to see this carry over into other studies and (IHME), at the University of Washington, predicts that into the future when we’re not in a pandemic situation.” COVID-19 deaths in Brazil will surpass US deaths by the However, Brown noted the safety implications inherent end of July. For companies launching COVID-19 clinical to a potential vaccine, which would go to hundreds of studies, Latin America may serve as a good location for millions of people in a short amount of time. “You need recruitment. Assuming that additional treatments for real-time safety data to be able to asses what’s going COVID-19 enter the market, and hopefully, a safe an on, nobody is really talking about that yet. Knowing effective vaccine, manufacturing and distribution will that vaccines are some of the less profitable products be the next big challenge. Regulators in Latin America the biopharma industry makes, maintaining a low-cost and elsewhere must be “willing to use stickers, for safety system for a low margin product, or even a loss- instance, they will have to be tolerant with some text making product, will be key.” deviations, and maybe they can consider facilitating
July 2020 | In Vivo | 13 WORLD VISION 360˚ China Turns COVID-19 Crisis Into A Global Health Care Opportunity
BY ASHLEY YEO - Better health care in line with standards delivered in other markets is increasingly demanded in China, where the use of digital technologies is both higher and better accepted than in many other parts of the world. Executive Summary Another important step has - Renewed attention to primary care needs has resulted in a long-overdue been taken under the Healthy law on promoting basic medical and health care needs, which continues the China initiative, with the momentum started in 2016 with the Healthy China 2030 Vision for Health implementation on June 1 of a Care. basic law on access to health care. This provides additional - China’s impetus toward ensuring greater access to health care comes as it tailwind for a health system that appeared to efficiently contain seeks to eliminate COVID-19 within its borders, having at one time seemed its coronavirus outbreak and is likely to suffer a long-term and much more costly episode of infection. now making further structural improvements. Amidst the frequent criticism of how China dealt initially with the outbreak of coronavirus in early 2020, and the uncertainty in many quarters over the precise origins, timings and sequence of events in 2019 that led to the pandemic, one thing is certain: China’s decisive action in and beyond Wuhan in late January could have been a lesson to economies yet to be hit by COVID-19.
Many countries where infection spread did not use Wuhan as a blueprint for action, or not fast enough, which is one reason why global infections have continued to rise. In early June, the infection rate was nearing seven million, and deaths 400,000 globally. In China, the respective figures on 31 May were 83,000 and 4,600, as claimed officially in the State Council Information Office
July 2020 | In Vivo | 14 WORLD VISION 360˚ of the People’s Republic of China’s report, Fighting A Health Care System In Need Of Attention Covid-19 – China in Action. The performance was more remarkable as China’s health care system has widely recognized difficulties The report was published in the first week of June. and problems within it, Beckett said in an interview with The 73rd World Health Assembly meeting of the WHO In Vivo. These are notably the lack of primary care, the concluded not three weeks earlier, with no promise absence of GPs and hugely over-crowded hospitals. that China would approve an independent investigation In times of public health crises, when resources are into COVID-19, as demanded by the EU and Australia. stretched, such inadequacies are highlighted. With no Instead, President Xi Jinping listed 11 internal proposals system of GPs or pharmacists to cope with minor health and measures in his speech opening the WHA. These care issues, all patients gravitate towards hospitals, are a focus of the official report, which congratulates using up the capacity that is needed desperately in a the Chinese people for joining together as one to pandemic. contain the spread of the virus. These underlying issues create a health care system Viewed from outside, while China praises its efficient with structural difficulties and challenges. The latest system and central authorities for exercising overall WHO Global Health Observatory (GHO) data show that command, there is a broad international consensus while Germany has 4.2 doctors per 1,000 of population, that the county’s very early handling of the outbreak the UK 2.8 and the US 2.5, in China the rate is just 1.78 locally was poor. Some viewed China as slow to react, per 1,000 of population. according to Nick Beckett, co-head of the Life Sciences & Healthcare Group and managing partner in Beijing at In many ways the structures in China have simply not global law firm CMS. Beckett commented that China’s caught up with other markets, and not just in primary administration felt it had done a good job responding, if care doctor numbers. There is no proper training perhaps not quickly enough. system, no major medical specialty institutions, no regular fora of experts coming together to discuss In fact, once the machinery of government got going, it topics in modern medicine, and no pooling of intellect made good progress and was impressive in successfully and talent. All the learning happens in the field and on isolating the first novel coronavirus strain on 7 January, the job. It is both a waste of opportunity and misuse locking down in Wuhan on 23 January and quarantining of skills, when qualified cardiologists, for instance, are 50 million people rapidly in Wuhan and surrounding having to spend 30% of their time dealing with minor cities, and building a 1,000-bed Huoshenshan Hospital ailments. in just 10 days, for instance. The renewed concerns over virus spread in Beijing in mid-June are apparently being A New Law To Bring Overdue Change addressed in a similarly focused manner. But the ground has now been laid for change, following the implementation on 1 June of China’s In addition, the National Medical Products first fundamental and comprehensive law on basic Administration (NMPA) fast tracked the approval of four medical and health care. The law was approved during novel coronavirus test kits from four local companies a bimonthly session of the National People’s Congress to boost capacity for producing virus nucleic acid test Standing Committee in December 2019. It aims to kits. In hindsight, the massive testing program, hospital promote medical and health care matters, improve building and control actions show China, in all, did access to basic medical and health care services and an effective job, especially when viewed against the build a “healthy China.” performance of the US, say, in attempting to control the infection, Beckett notes. Empowering medical institutions, upgrading professional training, and providing accurate health In addition, many countries have valued China’s care information to the public are other elements of the sharing of its knowledge of novel coronavirus and law. Furthermore, medical workers who choose to work its experiences. The country’s exports of personal in local communities and poorer, remote areas will protective equipment (PPE) have been both significant qualify for higher remuneration and allowances, and and positively received. China’s COVID-19 focus is greater career development opportunities. The law also now on preventing renewed spikes of the kind seen in encourages improved health education at schools and Shulan in mid-May; and on developing a vaccine, where universities. Medical and health care education has long it is reported that Chinese researchers are progressing been a missing part of the picture in China. well on two coronavirus vaccine candidates. Both the government and the public have been pushing for more holistic health care, from prevention to detection to treatment, as well as the provision of a
July 2020 | In Vivo | 15 WORLD VISION 360˚
“The government and the public have been pushing for more holistic health care, from prevention to detection to treatment.”
Nick Beckett
better all-round education in health matters. This law the patient-user knows there is not a human at the on promotion of basic medical and heath speaks very other end. “In that, they are receptive in a way that much to those needs,” said Beckett. While a lot of the other markets may not be,” Beckett said. domestic focus to date has been investing in biotech and pharma R&D – and less so in medtech – there has A recent example is the COVID-19 contact tracing been little focus on “health care.” system put in place in China in February in Hangzhou, headquarters city of Alibaba, and quickly rolled out to Overseas specialists will have an ongoing role in helping the all 200 cities in China. To prove their disease status, China meet these newly identified and acknowledged individuals had to download an app, hosted by Alibaba, needs. Just as China wants its own talent to return Tencent and Baidu, which displayed their status. This and help build such systems, so it also sees the need was determined after they had input information, to leverage western knowledge and talent to help in including close contacts. In turn, this gave them a that task. The increasing use of English, in the main QR code; and to be able to move around, a green cities at least, is down to children being taught it much code (“disease free”) was required to be shown to the earlier, as well as to the younger population being authorities at checkpoints. more receptive to western influences. There has been a relaxation over time of restrictions on certain elements This QR color-coded system was seemingly well of English language culture. received by the Chinese, who have become used to such technologies. No one complained about privacy Digital Upsurge In An Already Receptive or the government overreaching its powers, Beckett Population observed. Going beyond coronavirus, there are notions One very clear positive to emerge from the pandemic that the same QR technology will be used to create is a wider recognition of the value of telecare and permanent health trackers, which will integrate with telemedicine, said Beckett. In China, the JD.com online other parts of the system. This is more ambitious and retailer’s JD Health platform has seen daily online could be seen as more personally invasive. But equally, consultations increase from 10,000 in the pre-COVID the Chinese people might accept it without too great a period to 150,000 in its post-pandemic recovery period. concern. Patients are increasingly comfortable accessing health care online, a trend now also being exploited by rival Chinese Lessons platforms from Tencent Holdings and Alibaba Inc. In all, it seems COVID-19 has taught China many things. The country has learnt that it could do better, and this They are following the trend set by WePay and Alipay, is broached in specific measures in the law on basic China’s leading online banks, the success of which in medical and health care access. People are ever more revolutionizing banking in the early 2000s has seen aware that basic medical care provisions and the need credit cards bypassed. Just as online banking has to guarantee drug supplies are not high enough up supplanted much of the traditional banking activity, the domestic agenda. Alongside the law, certain lower so virtual health care has evolved to fill the gaps in level guidances on building intelligent hospitals, and traditional health care, such as the lack of primary care. spot checks on medical devices, in line with concerns These private company platforms are tending to fulfil over the quality of some PPE and face masks, are being the role of what would be the GP in other markets, with proposed. much of their care being delivered through artificial intelligence tools. On the other hand, there is considerable pride locally, and the administration’s successful testing of some The result has been a “tech savvy” audience that is 10 million people in and beyond Wuhan in a mere few receptive to the delivery of health care, and diagnostic days is one source of that. In May, the government and treatment services though online means, even if announced it was able to perform over 1.5 million
July 2020 | In Vivo | 16 WORLD VISION 360˚
COVID-19 serology tests per day. The achievement But there should be a relatively short-term effect, with of the local industry in being able to mobilize rapidly improvements expected in 2022. to produce millions of pieces of PPE daily is similarly impressive. It is all part of the China model, says This should not alter perspectives about China as a Beckett. “When China sets itself a task, it does it market. While there have been notable changes in trade very effectively, be it in locking down businesses, flows in health care and medtech, COVID-19 is a global municipalities, provinces or even the country. And it issue. The world is still trying to cope with seeing supply can re-open at the same speed and get business going chains disrupted in a major way. The rest of calendar again,” he said. 2020 will be challenging for all medtechs globally, partly because of turmoil in their own markets. But China is During COVID-19, the life sciences industry held up well coming out of the turmoil more quickly than others, and in China’s eyes, so any financial support and grants as a destination market for medtechs, it presents the largely went to other industries. But the government same if not better opportunities in areas like telehealth. has introduced a program whereby companies are not required to pay national insurance, a scheme that An Attractive Market In Waiting applies to all industries. “The Chinese market is still just as attractive to multinational companies, although it may take Getting Back To Normal businesses a year to get themselves back to a position Attention now turns to bringing elective care back to of normality in their own markets and regarding their more normal levels. There was sharp decline in certain own workforces, in order to be able to seize these elective procedures, and a consequent decline in opportunities,” said Beckett. procurement of medical devices during the outbreak in China: interventional device procurement shrunk 40- Certain macro issues, such as the ongoing trade dispute 80% in Q1 2020. But a gradual recovery is underway in with the US, the latter’s claims about the outbreak of the procurement of medical devices, although Beckett COVID-19, China’s refusal thus far to open up the issue does not believe a full catch-up of the lost volumes will to an independent investigation, its apparent bid to be achieved this year. “In some areas of high-volume end the “one China, two systems” policy in the case of consumables, there is an expectation of a continued Hong Kong, and its activity in the South Sea, observed contraction of perhaps 20% for the whole year,” he nervously from afar, obviously engender feelings of ventured. unease in the business community.
This is compounded by expected short-term declines But at a commercial level, China still incentivizes in health care budgets. GDP is expected to grow by multinationals to fairly access its market. Moreover, it between 1% and 2.3% in 2020, down from 6% last year, knows that western companies would find it difficult so health care will have lower spending. Medical device to consider not going there, in view of its lucrative and prices will come under pressure as a consequence. growing market in life sciences.
“For China, being seen as a leading force in health care globally would be very important.”
China also, usually, takes a long-term and pragmatic, big will be welcomed by a large and often underserved picture view of what it does. The US threat to withdraw population. COVID-19 has shone a powerful light on funding and its membership of the WHO – with which telemedicine and digital capabilities generally, and it “terminated” its relationship on 29 May, has opened these are areas where China has both the technology up the path for China to assume the putative lead role and a receptive market. on global health care matters. “For China, being seen as a leading force in health care globally would be very Similarly, its readiness to embark on app-based health important,” said Beckett. care delivery puts it in a good position as needs continue to evolve and grow. China has achieved a lot in Back on the domestic front, the beginnings of a move a relatively short time, but as the administration might to a better system for the delivery of basic health care agree, more still needs to be done.
July 2020 | In Vivo | 17 WORLD VISION 360˚ Regulatory Harmonization Makes Big Strides In Africa
BY IAN SCHOFIELD - Research has shown that the introduction of new vaccines and medicines in poor countries can take four to seven years longer on average in poorer countries than in richer ones. Executive Summary Last month a drug for - The new Marketing Authorization for Global Health Products procedure is the prevention of uterine the latest development in an international drive to build up drug regulatory haemorrhage became the first capacity in resource-poor countries and ensure that new, high-quality drugs product to be approved under a can be evaluated, approved and delivered to patients more quickly. novel scheme designed to speed up access to medicines in low - While regulatory alignment and harmonization efforts continue at regional and middle-income countries, particularly those in sub-Saharan community level, efforts are under way to set up a new African Medicines Africa. Agency.
Ferring Pharmaceuticals AS’s heat-stable formulation of carbocetin was authorized in Switzerland using the new Marketing Authorization for Global Health Products (MAGHP) procedure. It will now undergo rapid assessments in seven participating African countries, based on the Swiss approval dossier.
The new formulation, which was added to the World Health Organization’s Essential Medicines List (EML) last year, was developed by Ferring to address problems with refrigeration and cold-chain transport of post-partum haemorrhage (PPH) medicines in low and middle-income countries (LMICs).
July 2020 | In Vivo | 18 WORLD VISION 360˚
Carbocetin is intended for PPH prevention in settings The reasons for this are manifold, but those cited by where oxytocin is unavailable, or its quality cannot the founders of the AMRH included different regulatory not be guaranteed. Preventive treatments for PPH are standards and requirements among countries, limited desperately needed: the condition causes some 70,000 resources and technical capabilities, and a failure to deaths each year, 99% of them in LMICs, and most of leverage review work already done by the WHO and them preventable, according to Ferring. better resourced NRAs. Moreover, there was a lack of clarity over the roles of the various national regulatory Dr Yeshita Pujar, consultant gynaecologist-obstetrician authorities and ethics committees in the area of clinical at India’s Kles Prabhakar Kore Hospital & Medical trial authorization. Research Centre, said the product would “play an important role in PPH prevention in countries which Because of the number of countries in sub-Saharan carry the greatest burden of maternal mortality.” Africa, and the often huge geographical distances between them, regulatory harmonization efforts are Under the MAGHD procedure, the regular Swiss being conducted chiefly at the regional level, using the marketing authorization (MA) procedure is followed, already established “regional economic communities” with applicants being asked to notify the regulator, (RECs) to develop ways of sharing information and Swissmedic, before the planned dossier submission experience and working together on regulatory date. This allows the necessary resources to be assessments. The ultimate aim of the project is to have mobilized and African national regulatory agencies between five and 10 RECs covering the entire African (NRAs) to be involved. continent, with common documentation, procedures and decision-making frameworks. Resources will In the case of carbocetin, the countries that took part be pooled and information shared, while drug in the process are Uganda, Kenya, Tanzania (mainland manufacturers will face just one set of requirements and Zanzibar), South Sudan, Nigeria, Ethiopia and the and have to prepare only dossier in each REC. Democratic Republic of Congo, which have 90 days to take their own local approval decisions. To road-test the initiative, a pilot project on joint assessments was carried out in 2015-2016 in the The African Regulatory Harmonization East African Community, which comprises Burundi, Initiative Kenya, Rwanda, South Sudan (since 2016), Tanzania The MAGHD approval is the latest development in an and Uganda. This showed that the median timeline international drive to build up drug regulatory capacity from dossier submission to national marketing in resource-poor countries and ensure that new, high- authorizations fell to seven months from the one to two quality drugs can be evaluated, approved and delivered years that would typically have been the case when the to patients more quickly. The procedure was first agencies conducted their assessments separately. established in 2017 as part of the African Medicines Regulatory Harmonization (AMRH) initiative, which aims As a result of the pilot, it was decided to extend the to strengthen and align regulatory practices in sub- AMRH exercise to other African regions and also to Saharan Africa. The AMRH is coordinated by the African cover clinical trial approval procedures and drug Union’s technical body, the New Partnership for Africa’s safety monitoring and reporting as well as marketing Development (NEPAD). authorization activities.
Partners in the AMRH include the WHO, the African ZaZiBoNa Expands Collaborative Assessments Union Commission (AUC), the Bill and Melinda Other regional communities are now building up their Gates Foundation (BMGF), the World Bank, the UK own regulatory networks as part of the AMRH. One of Department for International Development (DFID), the the most prominent is the ZaZiBoNa group, which is US government, and the Global Alliance for Vaccines part of the 14-country Southern African Development and Immunization (Gavi). Community (SADC) and has implemented its own Collaborative Medicines Registration Procedure under The creation of the AMRH was driven by the need to which the national regulatory authorities jointly assess remove the barriers that hinder patient access to health medicines for registration procedure. ZaZiBoNa was care products, a problem that afflicts many LMICs but originally formed by Zambia, Zimbabwe, Botswana and is particularly pressing in sub-Saharan Africa. Research Namibia. But in May 2020 the Tanzania Medicines and has shown that the introduction of new vaccines and Medical Devices Authority (TMDA) announced that it medicines in poor countries can take four to seven had now expanded to include five more of the SADC years longer on average in poorer countries than in countries: Tanzania, the Democratic Republic of Congo, richer ones. Malawi, Mozambique and South Africa.
July 2020 | In Vivo | 19 WORLD VISION 360˚
The remaining six SADC states do not play an active said this was “a milestone achievement.” Strong part in dossier assessment but are involved in training national regulatory systems, Moeti said, were “critically programs and information sharing on products that important to ensure that when people seek treatment, are approved through the collaborative procedure, they receive effective medication and are safe from the TMDA said. They are also expected eventually to harm.” take an active role, depending on their resources and capabilities. The WHO believes this development will encourage other African countries to invest in building up their The aim of the ZaZiBoNa process is to promote a regulatory systems. “It should also serve to promote collaboration model and facilitate access to high-quality confidence, trust and further reliance on authorities medicines through work sharing in the assessment of attaining this level of maturity,” according to Mariângela medicines and inspections of manufacturing and testing Simão, WHO assistant director general for access to facilities. “It is envisaged that manufacturers of needed medicines and health products. medicines will benefit from accelerated registration processes, a single set of queries during the registration The evaluations of the Ghanaian agency were carried process and in principle harmonized registration out in 2014, 2015 and 2019 using the WHO’s Global decisions, which will facilitate easier review of any post- Benchmarking Tool (GBT), the primary means by which registration variations,” said the TMDA. the organization objectively evaluates regulatory systems. Products that meet the assessment criteria are granted individual approvals by regulatory bodies in those The WHO’s classification system begins with Level 1, countries where applications for registration were where only some elements of regulation exist in a submitted in at least two of the participating countries particular country, and goes up to Level 4, where an (in the common technical document format). Where agency operates at “an advanced level of performance necessary, variations to marketing authorizations can and continuous improvement.” The GBT is currently also be handled through the same process. The focus is used to evaluate regulatory systems for medicines, mainly on 10 priority diseases identified by the SADC as vaccines and blood products, but work is under way well as reproductive health products. to integrate medical diagnostics (including in vitro diagnostics) into the system by the end of 2020. Medicines that have been approved by a “stringent regulatory authority” (SRA; a term that is now being New Medicines Agency replaced by “WHO-listed authority”) are eligible for an While regulatory alignment and harmonization efforts abridged review process “provided there is access to continue at regional community level, efforts are under the full assessment reports on which the authorisation way to set up a new African Medicines Agency. by the respective SRA was based,” the TMDA added. The AMA, which was originally conceived back in The ZaZiBoNa procedure is not for use by generic drugs 2010, is not intended to be a stand-alone agency that have been prequalified by the WHO, as these can responsible for medicines regulation across the benefit from the accelerated WHO PQ Collaborative continent, and it will not replace the existing national Registration Process. or regional regulators. Instead, the agency is envisaged as a coordinating body that will help to promote the Regulatory Milestone For Ghana adoption and harmonization of medical product While regional initiatives are continuing to flourish, regulatory policies, standards and guidelines at regional individual national regulators are also taking steps to level. As well as coordinating existing harmonization strengthen their internal capacity to help ensure the initiatives being undertaken by the RECs and by regional safety, quality and efficacy of medicines manufactured, health organizations (RHOs), it will provide input imported or distributed within their countries. The into regulatory actions, emerging health issues and latest regulator to announce such an upgrade is pandemics. the Ghana Food and Drugs Authority, which in May became the second in the WHO African Region to attain A key milestone in the development of the new “Maturity Level 3,” the second highest of the four-tier body came in May 2018 when health ministers of WHO classification of national drug regulatory systems. the 55-country African Union (AU) adopted the AMA The first country to achieve Level 3 ranking was Treaty (AMAT). Then in November 2019 the WHO and Tanzania, in November 2018. the AU signed a memorandum of understanding to formalize their cooperation in three areas: the ongoing Dr Matshidiso Moeti, WHO regional director for Africa, establishment of the AMA, strengthening disease
July 2020 | In Vivo | 20 WORLD VISION 360˚ control and prevention efforts, and implementing One regulatory response to the spread of the pandemic Universal Health Coverage across the continent. has been to take action to speed up reviews of clinical trial applications for potential COVID-19 products – Moussa Faki Mahamat, chair of the African Union vaccines, therapeutics and diagnostics – in African Commission, and Dr Tedros Adhanom Ghebreyesus, countries. “National regulatory authorities and national WHO director general, said at the time that this ethics committees from across Africa have agreed “deepened partnership” would “help to facilitate the to combine their expertise to expedite clinical trial necessary political support, and implementation of review and approvals for new multinational preventive, country-level interventions, needed to improve the diagnostic and therapeutic interventions to the health and well-being of people across the African COVID-19 pandemic,” the WHO announced in April. continent.” The decision to collaborate on the development of new Tedros said the WHO welcomed the AU’s decision to treatments and vaccines was taken at the last meeting endorse the treaty establishing the AMA and that it of the African Vaccines Regulatory Forum (AVAREF), one was “ready to provide further support to define the of the continental technical committees of the AMRH scope of activities and to provide high-quality technical initiative. AVAREF was set up by the WHO in 2006 as an expertise.” In particular, he said, “we are devoted informal capacity-building platform bringing together to creating an enabling environment to foster local African regulators and ethics committees in an effort to production, which is central to the African Medicines improve regulatory oversight of clinical trials in Africa. Agency’s work.” However, the new agency can only come into operation The approach proposed by AVAREF has already been once the governments of at least 15 of the 55 AU successfully used for vaccines against diseases such countries have both signed and ratified the treaty, and as meningitis, malaria, rotavirus, pneumococcal progress has been slow. Seventeen member states are pneumonia and Ebola virus. understood to have signed the treaty to date, the latest being Gabon in April, but only Rwanda has deposited its As is the case with regulatory initiatives at the regional instrument of ratification. level, the WHO stressed that the joint reviews of clinical trials under AVAREF would be “based on voluntary African politicians are keen for the process to be cooperation between the relevant national regulatory speeded up. In March, the health, labor and social authorities and ethics committees,” with each country affairs committee of the Pan-African Parliament (PAP) “solely responsible for granting regulatory approval.” convened a meeting to review the status of the treaty Importantly, it added, “this process retains country and to “sensitize representatives of the continental specific requirements so that participating agencies do parliament on the need to promote the ratification of not compromise protection of [their] citizens by a top- the treaty at national level, especially in the context of down approach.” the COVID-19 pandemic,” the parliament said. “As the world was starting to realize the devastating impact of Given the COVID-19-related restrictions on face-to- COVID-19, the PAP thought it was opportune to engage face meetings, the AVAREF member states will set up different stakeholders on the readiness of Africa’s an online (SharePoint) platform for conducting joint health sector and coordinated efforts,” the parliament reviews of proposed trials for therapeutic, diagnostic said in May. “In this regard, the PAP Committee on and preventive interventions related to the pandemic. Health invited NEPAD for a review and information National regulatory authorities, ethics committees session on the AMAT at a time when AU Member States and targeted ethics review boards in participating grapple with proliferation of falsified medical products countries will post their queries online for real-time that have adverse effects on the health of users. The responses from sponsors/applicants, while the AVAREF message to African Parliamentarians was to incite secretariat will convene and coordinate virtual meetings member states to ratify this treaty given its benefits for for participating countries to conduct joint reviews of Africans.” clinical trial applications on COVID-19.
COVID-19 Trials To Be Accelerated Virtual meetings will also be used to discuss how In the meantime Africa, like practically all other regions regulators and ethics committees can better prepare of the world, is having to deal with the impact of the for and respond to the COVID-19 pandemic. Regulatory coronavirus pandemic. As of 10 June, the total number authorities and ethics committees can use a separate of confirmed coronavirus cases had passed the 200,000 platform (MedNet) to share information on planned or mark, with more than 5,500 deaths recorded. ongoing clinical trials in their countries.
July 2020 | In Vivo | 21 WORLD VISION 360˚
Wider Boost For Trials? Trials Registry, only 38 – just 2.5% of the total – include Any encouragement to align COVID-19 clinical trial any African countries. Those that do include African practices is welcome and could also help to boost sites are found mainly in Egypt and South Africa, with the low numbers of trials that are carried out in the some taking place in Nigeria, Ghana, Tunisia, Kenya and continent in general. Zambia.
According to Jenniffer Mabuka, program manager at the “The figures above are sadly nothing new,” The Africa African Academy of Sciences (AAS), the conduct of trials Report said, noting that even before the pandemic, in African countries is hindered by “poor visibility of “despite the clear needs, under 5% of ICTRP-listed existing sites, limited infrastructure and unpredictable clinical trials typically involved African country clinical trial regulatory timelines.” participation.”
“Africa’s virtual absence from the clinical trials map It did note, though, that initiatives like AVAREF and the is a big problem,” Mabuka wrote in an article on The AAS’s Clinical Trials Community aimed to address and Conversation website in April. “The continent displays rectify this problem, and that other projects were under an incredible amount of genetic diversity. If this way. These include the COVID-19 Clinical Research diversity is not well represented in clinical trials, the trial Coalition, which has been set up to accelerate research findings cannot be generalised to large populations,” in countries with fragile health systems and vulnerable she declared. populations.
The academy has set up the Clinical Trials Community, Action will be needed at the political level too. “Every a platform that aims to increase the visibility of African country’s epidemic preparedness kit should contain trialists and sites, reduce duplication of effort, and funds set aside for clinical trials during epidemics provide access to regulatory and ethics committee or pandemics,” said Mabuka. “This would require requirements across countries. governments on the continent to evaluate their role and level of investment in the general area of clinical trials.” The paucity of trials is also the subject of a June 2020 Such a move, she said, would “augment the quality analysis by The Africa Report, which found that of the and quantity of clinical trials in the face of the constant 1,556 interventional clinical trials related to COVID-19 challenge of emerging and re-emerging infectious currently listed on the WHO’s International Clinical diseases as well as a steady rise in non-communicable diseases.”
July 2020 | In Vivo | 22 WORLD VISION 360˚ Four Digital Saviors Of Indian Pharma During COVID-19
BY VIBHA RAVI s private clinics shut down across India, patients could not get to health care facilities due to strict estrictions on movements and hospitals were hit by a government-mandated cessation Executive Summary of elective procedures as well as incidences of COVID-19 From digital marketing to among staff. The pharmaceutical industry has witnessed an payment systems, electronic unprecedentedA crisis during the pandemic-led lock-down in the country. solutions are aiding Indian pharma to ensure business Acute and sub-chronic segments saw a sharp dip in sales while the chronic continuity during the lockdown. segment also suffered. A report on the impact of COVID-19 on the practice New guidelines are spurring the of health care professionals (HCPs) by Cognitrex Consultants and SIHMRACI adoption of telemedicine. Digital tools are connecting companies Educations Pvt. Ltd. showed gynecologists saw a 40% decline in their patient to their distribution chains and base, while plastic surgeons saw a 90% fall. health care professionals. While some changes are here to stay, An initial assessment by IQVIA estimates that growth in the Indian others might not stick. pharmaceutical market could slide to 1-5% in 2020 from earlier predictions of over 10%, against the backdrop of the demand and supply disturbances. (Also see “COVID-19 Disruptions Could Lead To Sharp Slowdown In India Pharma Market” - Scrip, 8 May, 2020.)
Hit by the business disruptions, Indian pharmaceutical companies are now more willing to adopt and invest in digital solutions that will allow them to continue operating during such crises than they were in the pre-pandemic era.
July 2020 | In Vivo | 23 WORLD VISION 360˚
While cloud-based services and data helped visits by their medical representatives (MRs) are not continuation of clinical trials, and use of medtech like possible given the lock-down. remote monitoring devices in a health care setup ensured that risk to lives of the medical community The initial assessment by IQVIA revealed that while 77% minimized, the focus in this article is on the use of of HCPs believe it is important to maintain contact with digital enablers aiding pharma firms’ sales during pharma companies during the COVID 19 phase, only the pandemic. (Also see “Coronavirus Pandemic 64% of them were contacted by these companies. The Accelerating Shift To Digitally-Enabled Innovation” - data would have changed since, nevertheless it reveals HBW Insight, 2 Jun, 2020.) gaps in digital marketing strategies.
Digital modes of communication between a company Most companies are using simpler tools like text and and its distribution chain, its field force and HCPs, WhatsApp messages as well as emails to communicate and HCPs and patients, have helped. While some of directly with HCPs while webinars are being organized the tools or practices might be here to stay, others to provide HCPs with updates in their fields of are unlikely to entirely stick after conditions return to specialization along with information on the relevant normal, say experts. products of the sponsor.
In Vivo delves into four such solutions that have helped “A vast majority of pharma still believes that the crisis the industry maintain business continuity. is short-lived, and life will go back to normal very soon. Hence, they are not yet convinced about digital Digital Marketing transformation which is capital intensive in companies Unlike certain developed markets, companies in India that do not have that infrastructure. Companies depend to a significant extent on prescriptions by that do, are also still making half-baked attempts at HCPs, given that there are multiple companies selling engaging customers online with the belief that their a generic drug. The traditional reliance on HCPs has sales forces will return to the market soon enough,” resulted in a model which leverages a large sales/field said Salil Kallianpur, a former executive vice-president force to drive sales. at GlaxoSmithKline PLC in India who now runs a digital health consultancy. (Also see “COVID-19 and What While some companies have invested substantially in Doctors Expect From Pharma In India” - Scrip, 1 Jun, digital marketing tools, others haven’t and so have been 2020.) unable to quickly pivot to them at a time when physical
“In a situation where brand recall is the only differentiator, MRs play a significant role in what a doctor prescribes. They develop a personal rapport with physicians and have deep insights. Then you have the issue of offering incentives to doctors, which might not be ethical but it’s a practice that is deeply entrenched in the system.”
Industry Expert
“Companies are taking a multichannel rather than “Information has always been available to HCPs, single channel approach during this time. However, in whether it’s via a website or product brochures, a country like India where labor costs are economical, however access and attention have been deficient,” he companies have always maintained a substantial field observed. force and this is unlikely to change in the near future despite the current challenges,” said Anup Soans, a Dr Vivek Shetty, joint replacement surgeon and former industry professional who is currently a digital consultant orthopedic at P D Hinduja National Hospital media enthusiast and author of multiple books. in Mumbai, said that a few companies like Zydus
July 2020 | In Vivo | 24 WORLD VISION 360˚ group’s Cadila Healthcare Ltd. have sponsored webinars Normally, private clinics prefer cash payments, but and it came to a point where two to three were being patients are insisting on using digital apps since the organized every day, but he feels that this strategy has lock-down has made cash withdrawals difficult. The run its course as fatigue for the medium has set in. Cognitrex-SIHMRACI study shows Google Pay and Paytm are preferred while internet banking is barely Digital modes of marketing are more likely to find favor used. among the newer generation of HCPs while the older generation might find it difficult to adapt, experts say. Apart from this, digital solutions are also being adopted in the pharmaceutical distribution chain. A Online Pharmacies And Consulting Platforms recent service by AIOCD-AWACS offers stockists of Online pharmacies like Netmeds, 1 mg, Medlife and pharmaceutical companies the option of using a digital PharmEasy offer customers the convenience of door- payments system instead of physical checks that are step delivery. Along with deep discounts, delivery has currently in use. been a draw for customers who worry about exposure to COVID-19 during a physical trip to the chemist. Apart from avoiding visits to a bank or ATM to physically deposit the checks, the free service also helps avoid Medlife serves customers in 29 states and 4,000 cities charges on bounced checks and payments made via fulfilling over 25,000 deliveries daily. CEO Ananth cards. Additionally, reminders are sent to stockists to Narayanan recently told local media that the online maintain an account balance in line with the credit limit pharmacy is looking to hire delivery staff as there has assigned to them by a clearing and forwarding agent been an up to 200% upsurge in the number of orders, (CFA) appointed by the pharmaceutical company. while deliveries are at 60-70% of what it used to fulfill. “Normally, a CFA has post-dated checks given by In fact, demand has surged to an extent where online stockists based on the credit limit fixed for each pharmacies are now cutting marketing spends and stockist. If a CFA sells products of 50 pharma companies even offering lower discounts to customers as they are and supplies to 50 stockists of each company and there assured of sales. Strong growth has been forecast for are two to three billing cycles in a month, which is the e-pharmacy market in India. generally the case, the CFA has to deposit 5,000-7,500 checks at a bank in just one month,” Rakesh Dave, Digital platforms like Practo, Lybrate, Ask Apollo and president of market research agency AIOCD AWACS, Just Doc have helped HCPs who run private clinics to said. keep consultations going at a time when clinics are shut or patients are unable to reach them due to restrictions “Imagine the hardship of doing so these days and the on movements. Even online pharmacy 1mg, which now time taken for a check to clear. Instead of that, we have also offers remote consultations, has seen a quantum details of each stockists’s current account details on our jump in the number of paying customers. portal, a CFA raises an invoice, the stockist gets an alert and dues are cleared smoothly,” he added. RedSeer Consulting has upped its estimate of the global digital health market to $25bn in FY25, compared with Stockists of some top pharmaceutical companies its pre-COVID-19 estimate of $19bn, with medicine like Sun Pharmaceutical Industries Ltd., the Indian delivery continuing to comprise a large share of the subsidiary of Abbott Laboratories Inc., Mankind Pharma market. India’s digital health market will expand to Ltd. and Cadila Healthcare are using this service and $4.5bn in this fiscal year, compared to $1.2bn in FY20, more are exploring the option driven by operational the consultancy said. continuity concerns, he added.
While regulation is still developing, most leading Teleconsulting e-pharmacies claimed to transact with customers Telemedicine is not new to the country, with Apollo through offline pharmacies and comply with the current Hospitals’ Apollo Telemedicine Networking Foundation laws. (Also see “India Pharma 2020: Trends That Can having been set up in 1999, however telemedicine Change Business Tempo” - Scrip, 8 Jan, 2020.) practice guidelines issued by the government on 28 March have helped drive its adoption during the Digital Payment Solutions nationwide lock-down. Digital payment gateways within teleconsulting and online pharmacy apps as well as independent digital So far operating in a regulatory grey area, telemedicine payment apps have kept transactions within the health has gained credence as registered medical practitioners care system going. are free to consult patients via phone, video, and
July 2020 | In Vivo | 25 WORLD VISION 360˚ chat applications including telemedicine platforms population against the 10 per 10,000 recommended by and WhatsApp. The guidelines, formulated by the the World Health Organization, telemedicine’s potential government think tank NITI Aayog, were notified under in India is huge. the Indian Medical Council (Professional Conduct, Etiquette, and Ethics Regulation, 2002). “Teleconsulting is a useful tool, especially for senior citizens and for those who have had surgical procedures Experts say teleconsulting has helped to keep sales recently. It’s particularly handy now for other patients going during the current lock-down when new as well who need follow-ups – in fact, my colleagues tell prescriptions dropped. IQVIA’s survey of 500 HCPs me that they’re likely to continue with this practice as it during 5-9 April, showed that while HCPs use multiple saves time and money for patients,” said Dr Vivek Shetty channels of communicating with customers, telephone of P D Hinduja National Hospital. calls and WhatsApp are preferred. However, it’s important that they have already met the Conducted among over 2,300 doctors in 16 Indian cities medical professional earlier and a physical examination between 24 March to 2 May, the Cognitrex-SIHMRACI has been done, he said. study shows that among the general practitioners surveyed. Setting up good teleconsulting facilities needs large - 60% communicated with their patients over the investments, which is easier for larger hospitals to phone do rather than smaller set-ups. Besides, patients’ - 22% via mobile applications (apps) like WhatsApp, unfamiliarity with technology is a barrier to adoption, Google Duo and Facebook messenger he added. - 15% through live video calling apps like Zoom, Skype and Microsoft Teams Dr Rakesh Ranjan, consulting neurosurgeon at Aditya Birla Memorial Hospital and Jupiter Hospital in Pune, On the other hand, hematologists interacted with agrees, saying it’s easier done at hospitals where patients on the phone 45% of the time while 35% were payments are handled smoothly and the patient-doctor contacted via mobile apps and 20% through live video interaction is recorded, but it’s not feasible if proper apps. data cannot be maintained, which is important from a legal point of view. It also doesn’t work if payments can’t In fact, state governments have been urged to drive be made by patients remotely. telemedicine use. Tweets from twitter handles of several state governments have shown or mentioned So, while telemedicine will not “substitute physical visits such consultations even in remote areas. With completely, more people will be forced to adopt it in a physician-population ratio of 7.6 per 10,000 of some form.”
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