Steve Usdin, Washington Editor
Biopharmaceutical Report III
The fight against COVID-19 is far from finished, but victory is close enough to start considering how the tools created to tame SARS-CoV2 will reshape the post-war world.
As with World War II and the Cold War, the world’s brightest minds have enlisted in a race to create tools to extinguish an existential danger. Intellect, enhanced by immense financial
resources and industrial capacity, is once again developing technologies that will be applied immediately and will also fundamentally change the course of history. As in past conflicts, technologies accelerated, perfected and proven in the pandemic crucible will become the springboards for innovation that will continue long after COVID-19 has been tamed. The intense focus and investments of World War II unlocked the power of the atom and produced technologies such as the jet engine, radar and computers that defined the second half of the twentieth century.
The modern pharmaceutical industry was also a direct result of the war, especially of a crash project to create processes to mass-produce penicillin. While Alexander Fleming had alerted the world to his serendipitous discovery in 1929, it took the pressure of war to transform it from a lab reagent into a medicine. In the early years of World War II, penicillin was so precious that researchers routinely recycled it from patients’ urine while British
and American businesses and governments invested massively to create industrial penicillin-production processes.
In 1943, a small citric acid manufacturer was one of about a dozen U.S. companies that bet their futures that they could develop and master the fermentation technology needed to make the first antibiotic. The gamble paid off for the allied soldiers — and for American industry. Medics had penicillin in their bags when they landed at Normandy and government contracts started the citric acid company, Charles Pfizer & Co. — today’s Pfizer Inc. (NYSE:PFE) — on the path to becoming the world’s largest pharmaceutical company.
"TECHNOLOGIES THAT ONLY A YEAR AGO SEEMED PROMISING BUT UNPROVEN, OR WERE DEEMED NICE-TO-HAVE BUT NOT ESSENTIAL, HAVE BECOME REAL AND ESSENTIAL"
The viral war of 2020 will have similar effects on medicine and the companies that make medicines. Technologies that only a year ago seemed promising but unproven, or were deemed nice-to-have but not essential, have become real and essential.
Companies that were on nobody’s short list of hot biotechs a year ago have soared. For example, Novavax Inc. (NASDAQ:NVAX), which in Spring 2019 was facing a delisting threat from NASDAQ, has received $1.6 billion from the U.S. government for COVID-19 vaccine R&D and manufacturing, while Canadian biotech AbCellera Biologics Inc. (NASDAQ:ABCL) has gone from relative obscurity to a $555 million IPO and a market cap of nearly $11 billion.
One of the silver linings of the pandemic could be the reinvigoration of two technologies that could be the most cost-effective in medicine, but that have languished as a result of broken business models: diagnostics and preventive vaccines. The spin-offs from advances in these two fields will improve the way diseases are defined, treated and prevented.
Technologies developed because of COVID-19 will make it possible to protect populations, making a repeat of this year’s disaster less likely. They will also empower individuals by giving them the ability to detect and monitor their medical conditions cheaply and easily at home. Processes accelerated in response to the pandemic will democratize care by validating and perfecting tools that make it easy for people and communities that have been left out to benefit from participation in biomedical research.
The decade of progress that has been compressed into the last 10 months hasn’t come easily or without missteps. Continued advances are not inevitable. Smart public policies, including government investments and regulations, will be needed to capitalize on the potential that has been unlocked.
The tragic failures to ramp-up production and administer therapeutic mAbs, along with bumbling vaccine administration programs that are leaving life-saving countermeasures in warehouses and vulnerable senior citizens camping overnight in lawn chairs, demonstrate that scientific and technological progress is not sufficient. To realize their promise,
advances in discovering, developing and manufacturing vaccines, therapies and diagnostics must be coupled to investments in public health and injections of competence and confidence in government institutions.
Biopharma companies, regulators, academic researchers, funders and payers must all be willing to change the way they operate to incorporate some of the collaborative behaviors showcased in the pandemic into their routine operations.
Seven decades after it helped turn penicillin from a lab tool into a pillar of medicine, Pfizer is again among a handful of companies that are taking enormous risks and executing beyond all expectations. Like penicillin in 1943, mRNA vaccine technology was conceived long
before COVID-19 struck, but in the absence of wartime conditions, it could have taken a decade or longer to make the progress that has been achieved in the past 10 months.
If the mRNA vaccines developed by partners BioNTech SE (NASDAQ:BNTX) and Pfizer, and by Moderna Inc. (NASDAQ:MRNA) and NIH’s National Institute of Allergy and Infectious Diseases, along with those coming from CureVac N.V. (NASDAQ:CVAC) and other
companies live up to their promise, the lag between identification of an antigen target and deployment of vaccines could be even shorter the next time the world is threatened by a pathogen with pandemic potential.
The ability to rapidly respond to mutations is a major advantage over other vaccine technologies, with benefits not only for pandemics but also for seasonal influenza and other outbreaks.
The successful development of mRNA vaccines is also a shot in the arm for the cancer vaccines BioNTech and Moderna were founded to develop.
The pandemic has been a proving ground for a variety of vaccine technologies beyond mRNA that, combined with investments in manufacturing capacity, could fuel public health gains for a generation as some of the hundreds of companies that have started down the path to creating a COVID-19 vaccine shift their sights onto other challenges.
The need for rapid screening and testing in a variety of settings has accelerated the development of diagnostic technologies, including tests based on CRISPR technology, the deployment of pooled testing protocols, and the dissemination of point-of-care tests.
"LIKE THE FRIENDSHIPS FORGED IN FOXHOLES, THE INTENSE COLLABORATION IN THE BATTLE AGAINST SARS-COV2 WILL NOT BE FORGOTTEN"
Diagnostic advances sparked by COVID-19 will be applied to battles against other infectious pathogens, especially antibiotic-resistant bacteria. The ability to quickly identify the pathogen in tests conducted in hospitals and physicians’ offices will make it possible to improve treatment of individual patients and stewardship programs that protect populations against resistant organisms.
The wave of in-home, point-of-care and lab-based diagnostics that are being developed for the novel coronavirus will be adapted, first to other infectious diseases, and later to other conditions.
Just as radar created for the battlefield made possible massive improvements in meteorology, diagnostic advances developed for COVID-19 will have broad effects beyond infectious diseases. New diagnostic technologies could extend the kinds of advances that
have occurred in cancer, including the redefinition of disease and the associated development of precision medicines, to other fields of medicine.
2020 has been the year of the master protocol.
While BioCentury has been reporting about and advocating wider use of master protocols for a decade, uptake outside of cancer has been slow. The urgency of the pandemic swept aside commercial concerns and funding constraints that have limited uptake of master protocols. Missteps on hydroxychloroquine and convalescent plasma, along with the massive missed opportunities caused by a plethora of underpowered and poorly designed trials have pounded home the importance of rigorous clinical research.
The U.K. RECOVERY trial, stood up in a matter of days, provided the first reliable demonstration that medicines can benefit COVID-19 patients, and just as importantly, solid data debunking therapies that had appeared promising based on anecdotes and underpowered studies. In the U.S., the ACTIV public-private partnership and the COVID R&D industry consortium turned to master protocols to test a wide range of therapies.
Having proved their value in the race to tame COVID-19, master protocols will become the tool of choice, not only for pandemic response, but also for determining the safety and efficacy of interventions targeting diseases and conditions that aren’t feasible to study with bespoke clinical trials. Prime candidates for master protocols include rare diseases, as
well as Alzheimer’s, diabetes and other common chronic diseases where the benefits of maintaining permanent trial infrastructure outweigh the costs.
Establishing ongoing master protocols for a wide range of diseases and conditions could be the first step in a much-needed modernization of the clinical trial enterprise. They will be platforms for advancing the use of adaptive trial designs, testing digital biomarkers, and especially for integrating clinical research into community settings. Realizing this potential will require substantial government funding, along with commitments to change on the part of physicians, hospitals, payers and biopharmaceutical companies.
Remote clinical trials technologies
In 2019 integrating remote data collection into clinical trials was an interesting idea, something added onto traditional trials or used experimentally.
The pandemic turned remote data collection and decentralized trials from niche ideas to mission-critical tools.
Just as diagnostic advances lead to the redefinition of disease, the ability to integrate data collection into routine care and to use sensors to gather data continuously rather than relying on tests conducted during visits to clinics will change the way diseases are defined and treated.
Expanded use of remote technology also has the power to reduce the disparities in clinical trial participation.
The COVID-19 experience has accelerated and will quickly make routine digital trial recruitment and integration of remote monitoring into trials. Together with digital sensors this means trials will become much more “real world.” This will lead to the redefinition of diseases as researchers and physicians move away from describing diseases based
on sporadic measurements at clinical visits and instead use continuous assessments of more relevant endpoints.
Scientific communication and collaboration
The sprint to create COVID-19 countermeasures was launched by a tweet on Jan. 10, 2020 from Edward Holmes, a scientist at the University of Sydney, reporting that he’d uploaded the genome sequence for the virus that causes COVID-19 to a public database. The sequence was the work of Zhang Yongzhen, a researcher in Shanghai who risked his career, and possibly his liberty, to release the information without waiting for Chinese government permission.
Presaging the spread of the virus itself, the tweet revealing that the sequence had been published flew around the world. For scientists in Oxford, Boston, Moscow and Mainz, the understated announcement was as loud as the crack of a starter’s pistol.
Within hours, researchers in academic labs and biotech companies were using the data to start designing vaccines and diagnostics and searching for therapies.
COVID-19 could have led governments around the world to set aside their differences long enough to defeat SARS-CoV2. That didn’t happen, but international collaboration and communication among scientists has been so critical to the pandemic response that new expectations have been created that will persist after the crisis has passed.
Life sciences researchers have been banging on the doors of academic journals for years, complaining that stodgy and snobby habits carried over from the paper and postage stamp era were unnecessarily slowing progress. Under the pressure of COVID, scientists have rushed the gates, publishing and critiquing research in real time on preprint servers rather
than allowing a handful of prestigious journals to act as gatekeepers, throttling the pace of progress to match the speed of academic peer review.
At biopharma companies, the coronavirus crisis prompted scientists to reach out to competitors and join with academics to form consortia, share data and collaborate.
When COVID-19 is in the rearview mirror, it will not be possible to maintain the 24/7 pace of activity and biopharma companies will revert to their traditional competitive postures.
Nonetheless, like the friendships forged in foxholes, the intense collaboration in the battle against SARS-CoV2 will not be forgotten. Patients, also, will not forget that medical product development that traditionally requires a decade or more can be accomplished in less than
New clauses in the social contract are being written that will require biopharma companies to expand their conceptions of the precompetitive space, and that will expand expectations about data-sharing and collaboration.
Beyond all of the scientific and technological progress, one of the most important lessons from the pandemic may be the need to restore confidence in science, to develop and adhere to sound principles for communicating about medicine and public health.
Signed commentaries do not necessarily reflect the views of BioCentury.
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