End of the beginning for COVID-19 vaccines

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It has been a hundred days and change since Chinese researchers posted the genetic sequence for the SARS-CoV2 virus to a public database, setting off the biggest and fastest race to create vaccines the world has ever seen. So far, at least six vaccines have made it into Phase I trials and a second cohort is poised to get into the clinic by the end of summer (see “COVID-19 Vaccines Timeline”).

Figure: Timeline of COVID-19 vaccines

Diagram shows select COVID-19 vaccines in or nearing the clinic. At least three companies say their vaccines could receive emergency use authorization (EUA) from FDA this fall. Half a dozen have disclosed plans to ramp up manufacturing in advance of EUA.

Source: company websites, SEC filings

We’ve reached the end of the beginning.

Beyond the astounding speed of vaccine development, one of the defining features of the race is diversity -- of vaccine modalities, types of organizations developing them, and geographic distribution of R&D and manufacturing.

Front-runners are headquartered in China, the U.S. and Europe.

Vaccine candidates in the clinic now are based on technologies that have never been used in an approved vaccine -- DNA and RNA -- as well as proven modalities such as inactivated virus and viral vectors.

Additional Phase I trials of vaccines based on these technologies, as well as protein-based and live-attenuated vaccine candidates, are set to start in the summer.

A curated list of preclinical and clinical vaccine candidates is available on BioCentury’s COVID-19 Resource Center.

Vaccine developers at the front of the pack range in size from behemoths like Pfizer Inc. (NYSE:PFE) and Johnson & Johnson (NYSE:JNJ) to the Jenner Institute at Oxford University that is partnered with Vaccitech Ltd., a biotech that has raised less than $50 million.

Like some of the other small entities, Oxford has teamed up with a pharma, AstraZeneca plc (LSE:AZN; NYSE:AZN), and is collaborating with Serum Institute of India, the world’s largest manufacturer by volume of vaccines (see “AstraZeneca to Make COVID-19 Vaccine” and “India Emerging as Major COVID-19 Vaccine Manufacturer”).

Other smaller players are partnering with government. Moderna is leaning heavily on NIH for clinical development and has received almost half a billion dollars from BARDA. CanSino Biologics Inc. (HKEX:6185) has backing from the Chinese government via the Academy of Military Medical Sciences’ Institute of Biotechnology.

While companies and academic groups are sprinting toward the finish line, they are competing against the virus rather than against each other. They are sharing data, and collaborating with each other, academic labs and government institutions to overcome common scientific and logistic challenges.

Two of the fiercest vaccine rivals, Sanofi and GlaxoSmithKline have set aside their competitive instincts to team up. GSK is providing an adjuvant that will stretch supplies of Sanofi’s vaccine and could provide broader protection in case the virus drifts (see “As COVID-19 Vaccines Progress, Science and Policy Questions Become More Urgent”).

Manufacturing bedfellows

Along with the scientific uncertainty and epidemiologic changes that could bedevil trials, manufacturing capacity is a critical rate-limiting factor for vaccines.

Pharmas like J&J, Sanofi and Pfizer can make large quantities of the vaccines they are developing.

Smaller players must partner with pharmas or buy capacity from CMOs.

The Oxford group has chosen the former strategy, while Moderna is pursing the latter (see “Lonza to Manufacture Moderna COVID-19 Vaccine”).

BARDA has placed big bets on Moderna Inc. (NASDAQ:MRNA) and J&J, and a smaller one on Sanofi (Euronext:SAN; NASDAQ:SNY). Whether and how generously they’ll support other COVID-19 vaccine manufacturers is unknown, and little is known about the adequacy of U.S. supplies of vials, syringes and distribution plans.

Europe hasn’t yet put in place a vaccine manufacturing strategy and China hasn’t announced its intentions or capabilities.

Europe, Japan, philanthropies including the Bill & Melinda Gates Foundation and the Wellcome Trust will make initial financial pledges for at-risk manufacturing on May 4. They’ll also reiterate commitments to global equitable access. They’re starting later than the U.S. and with underwhelming funding firepower (see “World Leaders -- Except U.S. and China -- Commit to Collaborate”).

Global manufacturing will be critical, as insurance against natural or man-made threats to facilities, and to ensure equitable access in the context of governments and regions prioritizing meeting the needs of their residents.

Clinical trial innovation will be critical. Master protocols are being designed and former FDA Commissioner Scott Gottlieb has proposed a “stepped wedge cluster” involving staggered vaccination of cohorts of people living in a city with an active outbreak (see “Master Protocols Emerge as a Critical Clinical Tool Against COVID-19”).

If clinical data look good, governments will be faced with difficult decisions about providing emergency access to unapproved vaccines.

The need to protect frontline healthcare workers will need to be balanced against the possibility that safety or efficacy problems could emerge that would harm individuals who received the vaccines and puncture the public confidence that is essential for successful vaccination campaigns.

Executive Editor Selina Koch contributed the graphic to this report.
Further analysis of the coronavirus crisis can be found at https://www.biocentury.com/coronavirus.

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