Collaboration, Speed, Scale: Lessons for Coronavirus and Beyond
With the current coronavirus pandemic, relying on traditional product development cycles to address the disease is proving to be woefully inadequate. Typically, research-based biopharmaceutical companies invest substantially in R&D with the promise of market exclusivity to recoup those investments. This results in carefully guarded data sets and often duplicated efforts, where first-to-market with a given class of compounds can mean billions. But with this pandemic, the public health objective of offering scaled-up technologies and treatments with speed and coordination trumps all other priorities — especially those of outmoded product development cycles.
What’s different about coronavirus
Our immediate priority is clear: prepare our health systems to weather the wave of cases that are quickly overwhelming care providers and medical facilities seeing a spike in coronavirus-related admissions. To do so we must ensure the delivery and allocation of personal protective equipment (PPE) and treatment supplies (ventilators, investigational drugs etc.). Simultaneously, we need to build an evidence base that will allow improved clinical outcomes, an understanding of what interventions are effective, and development of new products to help mitigate the effects of the virus. With COVID-19, we are truly “building the plane as we fly it,” to borrow a Silicon Valley adage. We face the dual mandates of figuring out how to best deliver care while simultaneously marshalling resources to improve it.
Learning from Ebola and H1N1
Recent infectious diseases outbreaks like the H1N1 Swine Flu or Ebola occurred when a foundation of knowledge and bodies of evidence already existed. Even though the H1N1 Swine Flu pandemic spread with similar aggression to COVID-19, immunity existed in sections of the population. Furthermore, H1N1 was more like other influenza A viruses than COVID-19 is like other coronaviruses (CITE). But the response to Ebola provides a better analogy to COVID-19.
Well over 1,000 peer-reviewed studies on Ebola, which was discovered in the 1970s, were available prior to the outbreak of the disease in 2014 Despite the early research on Ebola, the world was largely underprepared with robust product development by the time of the outbreak. However, one study found a 13x increase in publications on Ebola in just the first year of the outbreak, marking the beginning of an intensive effort to catalyze medical product development.Unfortunately, that effort came only after massive loss of life with more than 11,325 deaths and enormous societal disruption. And ultimately, product development stalled out as the spread of the disease was curbed. With COVID-19 we cannot afford to miss our window to deliver interventions before the pandemic wanes.
Learning from global health product development
High-quality clinical data traditionally has been predicated on anchoring medical product development with rigorous research methods. But the gold-standard of randomized placebo-controlled trials may not be possible as health systems globally are thrown into disarray with the overwhelming burden of patients. Instead as former FDA Commissioner, Scott Gottlieb has proposed, we should consider more flexible approaches, such as a compassionate use framework with a standardized protocol, that provide access to investigational drugs.
Today, new products are being developed with technologies advanced during the Ebola outbreak in 2014. For instance, the Johnson & Johnson AdVac and PER.C6 technologies which were used as platforms for the Ebola vaccine Ad26.ZEBOV. Furthermore, medical professionals and researchers are applying principles used over the last two decades in global health product development — focusing on collaboration, speed and scale — that offer a ray of hope as the world seeks to provide better, faster responses to epidemics such as COVID-19.
The coronavirus pandemic is a remarkable example of the contrast between how we develop products for wealthier markets and the approaches employed when there is not a robust commercial market. In this case, we have the budgets of traditional pharma coupled with the need for coordination that more often accompanies global health products.
When resources are scarce or time is limited, the coordination of efforts is critical. Rather than having multiple entities learning the same information about a given pathway or approach sequentially, using a forum to convene groups and share information in real time is critical. The COVID-19 Therapeutics Accelerator is a great ad hoc example of how that is being applied in the search for new COVID-19 therapies. This is a model that the Bill & Melinda Gates Foundation has already implemented in other disease areas where they are investing (such as the TB Drug Accelerator). The importance of these groups should not be underestimated. They can align disparate entities with common development protocols, streamline licensing between partners (particularly when combination products are involved), and open exchange of information on an ongoing basis.
When adequate products aren’t available to meet a significant medical need, speed must anchor global health product development. With tuberculosis, for example, in the early 2000s no new drug had been developed for the disease for nearly 50 years, and resistance to the standard treatment regimen was growing. In that context, a regulatory innovation initiative called the Critical Path for New TB Drug Regimens was born. This framework established a novel regimen development paradigm, where a sponsor develops a combination of drugs to be approved together (rather than as individual agents), saving almost two decades on the development end. Applied to coronavirus, we must study the effectiveness of promisingcombinations of therapies if safety can be established, thus avoiding the time it would take to approve multiple drugs individually. However, the FDA and other stringent regulatory authorities will still need to balance access with safety, particularly given the likely scale of use for these products.
Another lesson in speed came from the failings of the global response to the 2014 Ebola outbreak. At the World Economic Forum meeting in Davos in 2016, global shortcomings in the Ebola response prompted a call to better prepare vaccine development for epidemic threats. Follow-up recommendations served as the foundation for the Coalition for Epidemic Preparedness Innovations (CEPI), “a multilateral and collaborative approach, [whereby] the complexities of vaccine development and delivery [will] be addressed for the public good.” In other words, CEPI is designed to award grants for vaccine development that can address public health concerns where significant private investment does not exist.
CEPI’s formation required significant patient capital invested upfront (currently $750m of a $1bn stated goal) for the development of a rapid response vaccine platform to plug in new diseases (akin to how the flu vaccine is modified to address seasonal strains). However, given its ongoing work on a vaccine for Middle East Respiratory Syndrome (MERS), the group is already well positioned to coordinate development efforts for the new coronavirus. According to CEPI, the goal of having a COVID-19 vaccine ready for use in 12–18 months will cost an additional $2bn.
While a year sounds like a long time, given the remarkable speed of the coronavirus pandemic, this is lightning fast in the world of vaccine development. The International Federation of Pharmaceutical Manufacturers Federation (IFPMA), a global industry association representing research-based pharmaceutical companies, estimates a typical vaccine development program to take 10–15 years. With global coordination of efforts comes reduced inefficiencies and an opportunity to advance promising breakthroughs quickly.
Another area where the coronavirus response can and is learning from global health is scaling the innovations produced to deliver them quickly to those in need. Typical drug or vaccine development can include delays between the approval of a product and its availability, because manufacturing scale-up takes time and requires additional regulatory obligations. When abbreviated approval mechanisms are employed this can be of particular concern as the sponsor needs to begin manufacture and process scale up well before the results of the subsequent phase of development are available. To address this, JNJ is slated to manufacture its lead vaccine candidate at scale before it is proven in the clinic, in order to ensure the availability of sufficient volumes once the vaccine is approved.
In global health, the coordination between public entities and product developers often means that there is already alignment between the regulators, developers and purchasers about the target product profile and the process to bring it to market. This relationship is not necessarily so straightforward in purely commercial development approaches.
A good example of how global health has developed for scale is Gavi, the Vaccine Alliance, which sets out to shape vaccine markets to be more responsive to the needs of low-income countries. Among the tools that they have employed is the advanced market commitment (AMC) which secures vaccine manufacturers investments with volume guarantees from donors in order to lock in lower prices that emerging economies can afford. As the scale of public investment into coronavirus skyrockets the dynamics around access and affordability will no doubt come to the fore — particularly as more mature pharmaceutical markets will present enticing commercial opportunities for the successful COVID-19 product developers.
New Partnership Types
In global health, product development often includes a diversity of actors coming together, in part, because no one group has the resources to address the health challenges alone. A great example is the “product development partnership” (PDP) which is an organizational model that brings together the diversity of stakeholders to coordinate and drive medical product development. Created originally to support HIV vaccine development, it has been replicated across a number of infectious diseases where commercial markets were lagging. A unique feature of product development for global health is the diversity of stakeholders that come together — from academia to industry to donor organizations.
With the coronavirus there is a whole new set of partnerships not typically employed at this scale in global health — technology companies. To help combat COVID-19 there are a number of highly visible technology partnerships with potential to impact the product development landscape. IBM’s Summit, the world’s fastest supercomputer, for example, conducted a virtual high-throughput screening to simulate interactions between known compounds and SARS-CoV-2 binding to host cells. In just two days, the model identified and assessed 77 small-molecule drugs that could potentially inhibit the viral infection. Meanwhile DeepMind’s AlphaFold has released structural predictions of COVID-19 that could otherwise have taken months. All this while Eli Lilly and Canadian biotech company AbCellera have formed a partnership to identify and develop therapeutic antibodies to combat COVID-19 infection. Their stated goal: to be testing in the clinic in four months, an almost unheard-of timeline for scientific development.
In the face of the staggering medical and societal challenge coronavirus presents, healthcare entities have already stepped up in ways that were previously unimaginable. Private pharmaceutical and medical device companies have shifted their massive R&D engines toward identifying new therapies, vaccines and diagnostics with unprecedented timelines. This societal focus on medical product development has changed the rules of the game for coronavirus and hopefully for other diseases moving forward.
Ben Alsdurf is TLGG Consulting’s Health Care Practice Lead in the USA.