Transparency On COVID Vaccine Clinical Holds Needed, Sharfstein Says; US FDA Advisory Cmtes Offer Venue

Former acting Commissioner Josh Sharfstein argues that while agency officials have done a commendable job in overall communication on COVID vaccine development, more information is needed on the clinical holds.

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When he was acting FDA Commissioner in 2009, Sharfstein testified before the House about the H1N1 virus outbreak.

The US Food & Drug Administration needs to be more transparent about the details on the clinical holds that have been placed on COVID-19 vaccine candidates, including the reasons for imposing the holds and the data behind the decision to lift them, former FDA Acting Commissioner Josh Sharfstein said.

“Here we have the most critical vaccines in a long time, needing to be reviewed under incredibly time-sensitive circumstances, and we’re learning about problems with the trials through leaked explanations of investor phone calls,” he said during Prevision Policy/Friends of Cancer Research’s sixth annual Biopharma Congress. (To register and listen to all Biopharma Congress sessions, click here.)

“I just can’t say that makes sense to me. The public deserves to hear from FDA what’s going on: What the FDA is doing about the hold, and when the holds are resolved, why the FDA feels confident that the hold should be resolved.”

Sharfstein served as acting commissioner during the confirmation process for Margaret Hamburg and then served as her principal deputy. After leaving the agency, he headed Maryland’s health commission and is now vice dean for public health practice and community engagement at Johns Hopkins’ Bloomberg School of Public Health. His name has been floated as a commissioner candidate under the Biden Administration.

Sharfstein emphasized that he “fully believes” FDA is doing a “good job behind the scenes” in ensuring that any safety issues with the COVID-19 vaccines are addressed. “But I don’t think it does very much for public confidence to be getting these little snippets of information through investor phone calls.” Rather, he said, a “competent public health official” like Center for Biologics Evaluation & Research Director Peter Marks should “explain it to people.”

Here are the COVID-19 vaccine clinical holds known to date:

• The first, on AstraZeneca PLC’s candidate, was issued in early September due to an unexplained serious adverse event in a single participant in a UK-based Phase III study. The symptoms were consistent with transverse myelitis, an inflammation of the spinal cord. (Also see "AstraZeneca CEO: 2020 Approval For COVID Vaccine Still Possible" - Scrip, 10 Sep, 2020.) The hold was lifted in late October.

• Inovio Pharmaceuticals, Inc. announced a partial clinical hold on its Phase II/III trials on 28 September which are related to concerns with the company’s Cellectra 2000 delivery device that will be used in the trial. The Phase II segment of the trials is now ongoing, but the Phase III segment remains under partial clinical hold.  (Also see "Inovio COVID-19 Vaccine Trial Delayed By FDA Partial Hold" - Scrip, 28 Sep, 2020.)

• Johnson & Johnson’s Janssen “paused” its Phase III trials on 12 October after reports of a participant’s “unexplained illness.” The company noted that trial pauses – as opposed to a clinical hold imposed by regulators – are not usually made public. The company said it planned to resume the trials in late October but declined to provide details.  (Also see "Coronavirus Update: AstraZeneca’s Vaccine Trials Cleared To Restart In the US, J&J Prepares To Restart Its Vaccine Study" - Scrip, 26 Oct, 2020.)

Janssen’s decision not to release much information about the clinical trial pause raised red flags during an 30 October meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices. Members argued that transparency on safety issues is vital to instilling vaccine confidence.  (Also see "Lack Of Details On J&J COVID Vaccine Trial Safety Pause Raises ACIP Concerns About Transparency" - Pink Sheet, 4 Nov, 2020.)

In making a case for FDA to release information about the clinical trial holds, Sharfstein acknowledged that he is “fully aware that this is typically not what FDA does.” But he believes (as do many career FDA officials) that the regulations on what the agency can release about unapproved products should be changed: “The FDA should have the ability to explain what it thinks about clinical holds because it’s the FDA, and people really should hear from the FDA.”

At the same time, he suggested that the COVID-19 pandemic is an unpresented situation that requires unprecedented transparency. If asked by FDA, most vaccine sponsors would “waive any concerns about confidentiality” and allow the release of “basic information” about the clinical trials – without compromising patient privacy.

“That would give everyone a lot more confidence – and confidence is really going to be critical for products that millions and millions of Americans are going to have to take,” Sharfstein said.

Adcoms Can Reset The Narrative On Vaccines

Upcoming meetings of FDA’s Vaccines and Related Biological Products Advisory Committee to discuss the individual candidates will provide an opportunity to provide greater detail on the clinical holds, Sharftsein acknowledged.

Pfizer Inc./BioNTech SE’s vaccine will be reviewed by the committee on 10 December, FDA announced 20 November, the same day the sponsors sought an Emergency Use Authorization. Moderna, Inc. is close behind, and although the firm hasn’t filed for an EUA, Moncef Slaoui, Operation Warp Speed’s chief science adviser, said on ABC’s “This Week” on 22 October that the Moderna vaccine would get an FDA advisory committee review on 17 December.

Sharfstein acknowledged the high stakes around the advisory committee discussions: “The White House politicized this process in some ways by making completely unfounded accusations about the FDA that put everybody on edge.” Plus, “there’s a lot of stress people are feeling about the fact that states have jumped out and said that they want to do their own reviews,” he said. “It’s a little bit a sign of the political times.”

The VRBAC meetings offer an opportunity to reset that narrative and “validate the FDA’s thought process. If the FDA does a good job, with the decision-making and explaining itself, these will be extra boost of confidence around the country,” Sharfstein said. The agency should “provide the information that has been made public and be willing to explain its reasoning.”

“It’s science, and science sometimes has little confusing parts and they have to be explained. And for people to really have confidence, particularly for a lot of doctors to recommend it to their patients … having these kinds of dialogues in different places will be helpful.”