LONDON – CEOs of five leading biopharma companies have hit back against any suggestion COVID-19 vaccines and therapies could be approved in advance of phase III data, saying it is imperative the highest standards of quality, safety and efficacy are upheld everywhere.

The most important thing is to reinforce to the public the commitment to safety as the number one priority, said Kenneth Frazier, CEO of Merck & Co. Inc.

“We will not submit for emergency use authorization any vaccine candidate before we have a quantum of proof from phase III studies,” he said.

The sentiment was echoed by Albert Bourla, CEO of Pfizer Inc., who said, “Political pressure is irrelevant. We will never submit for approval any vaccine before we know it is safe. We will never cut corners – our phase III study will be the only one that will allow us to submit.”

The critical importance of gold standard phase III trials in dealing with the COVID-19 pandemic already has played out in the case of the anti-IL-6 antibody Actemra (tocilizumab), as Severin Schwan, CEO of Roche Holding AG noted.

“The idea was that for severe COVID-19 pneumonia patients who suffer an overreaction of the immune system, Actemra could help to dampen the immune response. We had a lot of anecdotes around that,” Schwan said.

But the phase III trial set up to confirm that did not read out positively. There has been an understandable rush to develop treatments for COVID-19, but Schwan said, “there’s no way we can lower the standards in conducting our trials. And the results of the Actemra trial demonstrate the point. Lots of people thought it would be effective as a monotherapy – this shows how important it is to do a randomized control trial,” he said.

The comments were made in an online briefing organized by the industry body, International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), to update on progress in developing vaccines and therapies, and warn against any regulatory shortcuts, after recent reports that the FDA is being leant on to approve a vaccine before the U.S. presidential election.

David Ricks, CEO of Eli Lilly and Co. and president of IFPMA, said a new style of engagement with the FDA, EMA and other regulators is certainly speeding things up. Typically, it takes two to three months to get a date to submit a file and discuss the data, and two to three months to get feedback. Now it is happening in a week.

“The procedural innovation has been strong,” Ricks said. But it is important to ensure the public understands no corners are being cut as a result. “We need to do randomized controlled trials that show efficacy,” said Ricks. “This industry and certainly our company, has no interest in getting approvals for ineffective products.”

Politicizing science

The refusal of companies to submit files to the FDA in advance of having phase III data provides cover for Stephen Hahn, FDA commissioner, who has been criticized by President Donald Trump for slow progress in approving new treatments for COVID-19.

In an interview with the Financial Times published on Aug. 30, Hahn is reported as saying the FDA is prepared to give emergency use authorizations before phase III trials are completed, but said it is up to companies to make an early application.

There is a further – geopolitical – dimension, with both Russia and China having approved vaccines in advance of phase III data.

The CEOs are concerned the all-too-public arm-twisting will lead to a loss of faith in the FDA and other regulators, and add to already significant public doubts about the safety of vaccines.

“I understand [the public] are skeptical, because science is so much politicized,” said Pfizer’s Bourla. “This is the worst situation the society can be in.”

One way to diffuse those concerns could be the introduction of extra transparency measures around emergency use authorizations. Bourla said he is “very much in favor” of that.

Merck’s Frazier agreed it may be a way to address doubts about vaccine safety. “It’s particularly important the data for emergency use authorizations is fully available and the scientific community can assure the public it has been looked at objectively,” Frazier said.

Based on his experience of how the FDA handled the application to approve his company’s antiviral drug, Veklury (remdesivir), Daniel O’Day, CEO of Gilead Sciences Inc., said there should be more effort to ensure the public understands getting emergency use approval is not trivial. The file for Veklury included data from three randomized controlled trials set up to assess if the product is effective against COVID-19.

“It is a very thorough process,” O’Day said. From a standing start as the pandemic took hold in January, the drug is now allowed for use in 50 countries.

Giving a progress update on the mRNA COVID-19 vaccine Pfizer is developing in collaboration with German biotech Biontech SE, Bourla reported that as of Sept. 2, the phase III trial has recruited 23,000 of 30,000 subjects. A significant number of those have already received the second dose.

The trial is randomized 1-to-1 vaccine to placebo. Now the wait is on to see if there are enough infections in the placebo arm to show the vaccine is protective. “We expect by October to have enough events to see if the product works or not,” Bourla said. “If enough events say it is safe and effective, we can submit [before the end] of October.”

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