Pharma R&D alliance to take on long-term pandemic preparedness
New industry organization will create a portfolio of Phase II-ready coronavirus, influenza therapies
A new industry organization will create a portfolio of Phase II-ready coronavirus, influenza therapies.
An alliance of R&D leaders of pharmaceutical companies is forming an organization focused on ensuring that the world is better prepared for future pandemics. The initiative is fueled by the urgency of the ongoing crisis, informed by lessons learned in the war against COVID-19, and motivated by scientists who know their industry is uniquely situated to protect global populations against a repeat catastrophe.
The organization is an extension of the COVID R&D Alliance that executives from over a dozen pharmas formed in the spring together with a handful of smaller biotechs and VCs, to coordinate and advance the industry’s pandemic response. The goal of the new enterprise is to create a portfolio of therapies, primarily small molecule drugs, that could be rapidly deployed while vaccines are under development, and after vaccines are deployed to treat individuals who are unable to receive or are not protected by vaccines. The emerging threat from SARS CoV-2 variants highlights the importance of therapeutics, even in the context of rapid vaccine development.
A working group of COVID R&D Alliance members has been meeting for several months to map out a strategy to turn the hastily assembled militia that came together in March 2020 into a confederation that can collaborate over the years-long timelines required to research and develop new medicines for future respiratory pandemics.
“We feel a great sense of urgency and that the work needs to move forward.”
The effort is propelled by the realization that if R&D on therapies for SARS and MERS had not slowed to a crawl after those outbreaks burned out there would likely have been far better medicines on hand when SARS-CoV-2 struck. Unlike vaccines and mAbs, it is impossible to develop new small molecule drugs from scratch quickly enough to respond to an unfolding pandemic – the work must be started years in advance.
While the group has discussed its plans with government officials and representatives of philanthropies, the pharma companies are not waiting for external leadership or funding.
Details of the new organization, including a name, are still under discussion, but there is a commitment to rapidly put the plans into effect, Elliott Levy, SVP of global development at Amgen Inc. (NASDAQ:AMGN) and a member of COVID R&D, told BioCentury.
“We feel a great sense of urgency and that the work needs to move forward. We hope to launch this organization in the relatively near future,” Levy said. “It has to be years and not decades before we have a library of Phase II-ready assets” that can be drawn on to combat future pandemics.
While vaccines will be critically important in a future pandemic, the experience of 2020 and the emergence of variants has removed any doubt that therapeutics remain essential, including small molecule drugs that can be mass produced and easily distributed. As well as downgrading from severe to mild disease , they can slow disease spread while vaccines are being developed and deployed, and treat individuals who are unprotected or unable to receive vaccines.
Based on past performance, there is a narrow window for standing up pandemic preparedness activities before competing priorities siphon away attention and resources. That window will likely slam shut as soon as an end to the current crisis is in sight.
Governments are unlikely to act quickly enough to seize the moment and they lack the expertise and capabilities industry has sharpened through decades of competitive pressure that allow companies to excel at discovering and developing drugs and vaccines.
Biopharma companies that accepted government leadership in the heat of the COVID-19 crisis are unlikely to commit resources and opportunity costs to a government-run program after the pandemic has waned. An effort designed by companies that harnesses both pre-competitive collaboration and competition around specific molecules has a far greater chance of success.
The COVID R&D Alliance’s first act
The new long-term pandemic response organization will build on the relationships forged in the COVID-19 crucible, including public-private partnerships and industry consortia.
Operation Warp Speed and the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) consortium created by NIH and the Foundation for the NIH (FNIH) have been in the public eye, and CEPI jumpstarted vaccine R&D. Two complementary industry-led consortia, the COVID-19 Therapeutics Accelerator and COVID R&D, have also been making important contributions.
COVID R&D, ACTIV and the Therapeutics Accelerator have overlapping memberships.
“The organization is envisioned to be a confederation within which all participants commit to a meaningful level of effort in preparing for the next pandemic.”
The COVID R&D Alliance’s accomplishments include launching COMMUNITY, an adaptive platform trial designed to evaluate multiple therapies in parallel across the spectrum of hospitalized COVID-19 patients. Amgen is sponsoring the study, which started in December 2020 with three immunomodulators from consortia members — Otezla apremilast from Amgen, Takhzyro lanadelumab from Takeda Pharmaceutical Co. Ltd. (Tokyo:4502; NYSE:TAK), and zilucoplan from UCB S.A. (Euronext:UCB).
COVID R&D established a screening platform that evaluated over 3,000 molecular candidates, including molecules submitted to a public portal maintained by BioCentury. The evaluation identified several candidates that have progressed to additional screening.
The alliance has taken a collaborative approach to data sharing and an expansive view about the scope of the pre-competitive space. This has included bringing together “experts in real-world data to share data and analytic resources and develop rapidly a body of real-world evidence around the natural history of COVID-19,” Levy said.
The long-term pandemic preparedness plan the COVID R&D Alliance is developing rests on three legs: creation of a pre-competitive space for developing and sharing resources; drug discovery and development by companies with requisite expertise; and funding to support an ecosystem, including smaller biotechs, capable of discovering and developing small molecule drugs.
It is focused on coronaviruses and influenza.
“We asked ourselves what would be the likely causative agent for the next global outbreak, and we decided to focus first on respiratory viruses, because they're more transmissible than viruses that travel via other routes,” Levy said. The group narrowed the focus to the “coronavirus and influenza virus families because they have been the source of three of the important outbreaks from novel agents in the last 20 years.”
While the “core activity is going to be the development of small molecule antivirals that are ready to be tested against a pathogen, the framework is broad enough that it will also support the development of other modalities, including monoclonal antibodies. We feel that there could be important benefits from sharing best practices in that area, even though the development timelines for those therapeutics are much shorter.”
COVID R&D has not disclosed the financial commitments that will be required from members of the new organization, nor the number of members. Levy said they will “establish effort levels that will be expected of each participant that collectively represents a substantial, all-of-industry response to the pandemic.”
Industry investments will be large enough to create a portfolio of drug candidates. The COVID-19 vaccine experience, especially the outstanding performance of unproven mRNA technology and the disappointing results with some tried-and-true technologies, has made clear the importance of investing in a portfolio of responses.
“The organization is envisioned to be a confederation within which all participants commit to a meaningful level of effort in preparing for the next pandemic,” Levy said. “All will contribute know-how and data and support the development of platform capabilities that in a pre-competitive way assist the entire sector.”
Commitment levels will be set at levels sufficient to “support the development of a robust portfolio of antiviral agents against conserved targets” of the coronavirus and influenza families, and to develop them through optimization to nonclinical toxicology in Phase I testing. They would be ready to be deployed in Phase II clinical trials in the setting of a new outbreak.
“The government doesn’t know at heart how to develop drugs – it’s not their ‘day job’ like industry folks.”
The organization will create and share centralized resources such as assays and other common standards for preclinical research, animal models, structural studies, databases and other resources that can advance the development of coronavirus and influenza therapies.
Companies that have active antiviral R&D programs will dedicate some of their activity to the new organization’s objectives. Member companies will also fund R&D conducted by companies that have relevant capabilities.
“Some companies will launch their own internal discovery efforts and seek to develop agents, many of which we envision will be against highly conserved viral targets like the polymerase and protease,” Levy said. “Other companies will choose to invest externally in what we hope and what we envision through external funding will become a robust ecosystem of smaller companies that are working in the same area.”
Companies will retain IP rights to the drugs they develop. Tools and data created as part of the pandemic preparedness organization’s pre-competitive activities will be shared across members.
Learning from COVID
The new organization will build on lessons learned in the COVID-19 response. Several companies, including some that are not COVID R&D Alliance members, have expressed frustration with the ways ACTIV and Warp Speed have managed the development of therapies.
Moncef Slaoui, who recently stepped down as scientific adviser and co-leader of Operation Warp Speed, acknowledged some missteps, especially regarding the conduct of clinical trials of therapies, in an exit interview with BioCentury.
Along with its successes in accelerating vaccine development, one of the overarching lessons from Warp Speed is the importance of placing organizations and individuals in leadership positions based on their deep expertise. Biopharmaceutical executives who have spent their careers discovering and developing drugs are going to make better decisions about executing pandemic drug development than academic or government scientists who have different areas of expertise.
“Industry has the greatest capability to discover, optimize and test novel therapeutics; that's what we do,” Levy said.
“Clearly there have been sparkling examples where government, academics and industry worked together on COVID,” especially some of the ACTIV initiatives and government funding for manufacturing, Keith Gottesdiener, president and CEO of Prime Medicine, Inc., told BioCentury.
Gottesdiener has been involved in both ACTIV and the COVID R&D Alliance. During a 16-year tenure at Merck ending in 2011, his responsibilities included developing vaccines and infectious disease therapies.
“The government doesn’t know at heart how to develop drugs – it’s not their ‘day job’ like industry folks,” Gottesdiener said. “They don’t have the expertise to identify, test, study or manufacture drugs or vaccines.” he added. “They really don’t live it,” like biopharmas do.
Gottesdiener emphasized he wasn’t seeking to “undervalue what government folks can do, but they really see things from an inside-the-government point of view and don’t fully value that people outside the government can do these things really, really well.”
Clinical trial networks
In planning the extension into long-term pandemic preparedness the COVID R&D working group has discussed the importance of modernizing clinical trials for infectious diseases, but has not determined what if anything it will do in the area. A central principal of the alliance’s COVID-19 strategy last year was to test molecules using platform trial designs.
“We recognize that there will be little value in developing a library of potentially useful compounds if there's no way to study them, so the organization has within scope the issue of clinical testing, but it would be premature to say exactly what it will do to address the problem there,” Levy told BioCentury.
The new organization plans to deploy some of its companies’ advocacy and regulatory expertise to advance pandemic preparedness. Clinical trials infrastructure, a high priority for Acting FDA Commissioner Janet Woodcock, may be an area that is ripe for collaboration between the industry group and government.
More broadly, the new organization will serve as a single point of contact and voice for government agencies and philanthropic organizations to communicate and collaborate with industry, Levy said. “We think that not only can we accelerate industry's work and make it more productive, we also can be of service to other sectors by joining forces to provide them with a trusted partner that they can work with in a productive way.”
The alliance is relying on governments, philanthropies and other organizations to address a number of critical aspects of pandemic preparedness that are outside its scope, such as creation of surge manufacturing capacity, tackling antimicrobial resistance, developing diagnostics to guide treatment decisions in a pandemic and global surveillance capabilities to detect emerging pathogens.