COVID-19 Vaccine Sponsors’ Pledge To Wait For Phase III Helps US FDA
Executive Summary
The move reduces the pressure on the companies to rush development, but also relieves burden on the FDA to approve a candidate too soon.
The pledge by multiple coronavirus vaccine developers to follow high development standards may alleviate as much pressure on the US Food and Drug Administration as it does on the individual companies pushing to make their products available.
Nine vaccine sponsor CEOs announced a non-binding commitment 8 September (see box) to always make the safety and well-being of vaccinated individuals a top priority, continue to adhere to high scientific and ethical standards for the conduct of clinical trials and the rigor of manufacturing processes, work to “ensure a sufficient supply and range of vaccine options,” and “only submit for approval or emergency use authorization after demonstrating safety and efficacy through a Phase III clinical study.”
Companies Signing The Coronavirus Vaccine Development Pledge
The final item may be the most important at the moment, as several companies are now conducting Phase III clinical trials and questions are circulating about whether there will be pressure on the FDA to clear a vaccine before the 3 November US presidential election.
A spokesperson for Pfizer, one of the companies that signed the pledge, said that the Phase III trial will be completed before the company and its partner BioNTech submit an application.
Jon Bigelow, executive director of the Coalition for Healthcare Communication, an organization of advertising, marketing, medical publishing, and other communicators, but which does not include pharma companies, said in a letter to industry leaders that “much as the companies want to be first to market with an effective vaccine, they realize that launching a vaccine that could cause serious adverse reactions when given to millions of patients, and/or that fails to protect against COVID-19, would badly damage their own reputations.”
“Apparently the biopharma companies realized they need to protect the FDA from the president – and perhaps from itself – at this critical juncture,” Bigelow wrote.
President Trump said 8 September that “a vaccine is looking very good for pretty soon.” Others have said approval or an EUA by that date likely will be very difficult. (Also see "Gottlieb: Staged Access To Coronavirus Vaccine Possible Through EUA" - Pink Sheet, 7 Sep, 2020.)
The pledge relieves some of the pressure on the companies to rush to finish their development programs before safety and efficacy are definitive.
But the commitment to wait until the end of Phase III to submit an application also removes a large burden from the FDA. The agency cannot approve or grant an EUA for a vaccine without a formal application, and while it may be viewing clinical data in real-time, there likely will be less temptation to move faster than warranted.
“The intent of the pledge is to help ensure public confidence in the rigorous scientific and regulatory processes by which COVID-19 vaccines are evaluated and may ultimately be approved,” Pfizer said.
FDA Commissioner Stephen Hahn garnered criticism when he stated in an interview that a vaccine could be approved or receive an EUA before Phase III trials are finished, even though it may depart from agency guidance. (Also see "US COVID Vaccine Early Distribution Plans Assume Emergency Use Authorization First" - Pink Sheet, 30 Aug, 2020.)
Novavax, another of the companies that signed the pledge, indicated that it would submit a vaccine application before the end of Phase III, if warranted. (Also see "Novavax Willing To Submit COVID-19 Vaccine Before Phase III Completed" - Pink Sheet, 1 Sep, 2020.)
Pharmaceutical Research and Manufacturers of America President and CEO Stephen Ubl also issued a statement supporting the pledge indicating that “industry sponsors will be confident in the safety and efficacy of any new vaccine based on data from rigorous, large clinical trials” before data is submitted to the FDA and other regulators.
“We’re confident science will win,” Ubl said.
In the days before the sponsors announced their pledge, the Biotechnology Innovation Organization also called for FDA to maintain its independence in order to maintain public trust in the vaccine process. (Also see "BIO Calls For Journal Publication Of COVID-19 Trial Data, Independent FDA" - Pink Sheet, 3 Sep, 2020.)
Pledge Should Not Be Necessary, Offit Says
Paul Offit, pediatrics professor at the Children’s Hospital of Philadelphia Division of Infectious Diseases, told the Pink Sheet in an interview that the pledge was a responsible thing to do and that it was nice to know that the industry was holding itself to a high standard. But he added that the letter should not have been necessary because it is the FDA’s job to stand between the public and the pharma industry. He said fact that the companies felt obligated to take the pledge indicates that there is distrust of the senior leadership at the FDA.
Offit has said that companies should commit to not sending applications until the Phase III clinical trials are completed.
Interestingly, the pledge makes several references to the FDA, but mentions no other global regulators by name, potentially more evidence that it is focused on concerns in the US.
The declarations include that the FDA has clear guidance on vaccine development based on scientific and medical principals and that large, high-quality, studies are necessary to gain approval. The companies said in the pledge that they would follow “guidance from expert regulatory authorities such as FDA.”
Pfizer said its trial is intended to meet FDA standards, but that the company’s “commitment to stand with science applies to regulatory filings globally.”
Questions about White House influence on FDA decisions intensified after the agency granted an emergency use authorization for convalescent plasma. The announcement of the decision included an overstatement of efficacy data by Hahn and others and came after Trump said the agency was moving slowly on purpose. (Also see "Plasma Authorization Raises Fears Of Politically-Influenced COVID-19 Vaccine Decisions, Compromised FDA" - Pink Sheet, 24 Aug, 2020.)
Hahn Continues Confidence Rebuilding Work
Also on 8 September, Hahn posted a series of tweets intended to highlight the FDA’s work related to coronavirus vaccines and help rebuild some of the lost public confidence.
Hahn reiterated that “only science and data will drive FDA’s decisions,” and that agency professional staff will authorize a vaccine only if its meets “the high standards that Americans expect for safety and effectiveness.” He also once again said the agency would not “cut corners.”
The tweets also reference FDA guidance with coronavirus vaccine safety and efficacy recommendations and remind the public that the Vaccines and Related Biological Products Advisory Committee will meet 22 October to discuss coronavirus vaccine development and other issues.
“We believe transparency in this process will help build confidence and provide greater understanding of this critical work,” Hahn said in one of the tweets.
The advisory committee meeting could be one of many in late 2020 as product-specific sessions could be added to deal with issues unique to individual candidates. (Also see "COVID-19 Vaccine Advisory Committee May Help Determine US FDA Approach To Licensure" - Pink Sheet, 27 Aug, 2020.)
The FDA vaccine guidance sets a 50% efficacy threshold, in part to expedite development, but also to avoid pressure to approve a potentially substandard product. (Also see "Coronavirus Vaccine Efficacy Rate Set At 50% Because That’s What US FDA ‘Could Tolerate’" - Pink Sheet, 8 Jul, 2020.)
Pfizer and Moderna are leading the race for vaccine approval. Both companies’ mRNA candidates are nearing their Phase III trial recruitment goals. Pfizer also remains on track to seek regulatory approval in October. (Also see "Pfizer CEO: Vaccine Could Be Ready In October But Won't Be Hurried By Political Pressure" - Scrip, 4 Sep, 2020.)