Pfizer vaccine trial bets on early victory against coronavirus, documents say

(Reuters) – Pfizer Inc is betting that its coronavirus vaccine candidate will show clear evidence of effectiveness early in its clinical trial, according to the company and internal documents reviewed by Reuters describing how the trial is being conducted.

In recent weeks, Pfizer has said that it should know by the end of October if the vaccine, developed in conjunction with Germany’s BioNTech SE, is safe and effective. If the vaccine is shown to work by then, Pfizer has said it will quickly seek regulatory approval. It has not said what data it would use.

President Donald Trump, who is seeking re-election, has said a vaccine to combat the coronavirus pandemic is possible ahead of the Nov. 3 vote in the United States, raising concerns about political interference. Scientists have questioned whether drug makers will have enough evidence to be successful at that point.

Pfizer’s clinical trial protocol describes to the company, scientists, and regulators how the drugmaker could demonstrate that its vaccine meets the efficacy and safety standards set by the US Food and Drug Administration.

A company’s protocol is submitted to the FDA for review and is overseen by an independent panel of experts known as the Data and Safety Monitoring Board.

The protocol calls for a first evaluation of the vaccine’s performance by the monitoring board after 32 trial participants became infected with the new coronavirus. So far, more than 29,000 people have enrolled in the trial that began in July, some receiving the vaccine and others receiving a placebo.

The FDA has said that a coronavirus vaccine must be shown to be at least 50 percent more effective than a placebo in a large-scale trial to be considered for approval. However, a smaller sample of infections in a clinical trial changes the estimate of how that standard is met, according to the researchers.

Pfizer’s vaccine would have to be at least 76.9% effective to show that it works based on 32 infections, according to their protocol. That would mean that no more than six of those coronavirus cases would have occurred among people who received the vaccine, the documents showed.

If the drug manufacturer’s vaccine does not meet the 76.9% efficacy target in this first interim analysis, it would face stricter thresholds of statistical significance during subsequent interim evaluations, said biostatisticians who reviewed the protocol.

Pfizer said its interim analyzes were designed to show conclusive evidence “as quickly as possible in the midst of the devastating pandemic if our vaccine meets the strict standards set by the FDA.” Pfizer did not say whether it would use an interim analysis as the basis for seeking approval.

The FDA declined to comment on whether it would consider such data sufficient for approval.

SUFFICIENT EVIDENCE?

Safety and data monitoring boards typically use interim reviews to determine whether an experimental drug appears safe and effective enough to continue a trial, or whether it should be stopped if a safety concern arises.

But if a vaccine meets FDA parameters in an interim review without any serious safety concerns, it might make sense to use it as the basis for authorization to help curb a pandemic that has killed some 940,000 people worldwide, he said. Thomas Lumley, chair of biostatistics at the University of Auckland in New Zealand.

Modern Inc , another leader in the vaccine race, told Reuters it would seek an emergency clearance from the FDA to use its vaccine in high-risk groups if a mid-term evaluation of its trial showed that its vaccine was at least 70 percent effective. effectiveness.

Moderna, which released its protocols Thursday, said its first interim analysis of 53 infections is likely to take place in November.

Some vaccine experts have said that drug manufacturers should wait for their final analyzes of more than 150 cases before seeking FDA approval. They point to the speed at which vaccines for COVID-19 are being developed, compressing what may be a decade-long process into months.

Relying on the more limited interim analyzes could overstate the efficacy of a vaccine simply because not enough trial participants got sick, they said. Moving faster through the testing process also means that a drug manufacturer could miss potential side effects that could materialize if testing was given more time.

“These interim analyzes have an intermittent signal of shortcuts,” said Eric Topol, director of the Scripps Translational Research Institute in La Jolla, California. “The security issues are lost and the benefits are very likely to be overstated.”

In addition to Pfizer and Moderna, Reuters reviewed clinical trial protocols for vaccine candidates developed by AstraZeneca Plc. and Johnson & Johnson . AstraZeneca established its first interim analysis when around 40 coronavirus infections were reported among the participants. Her trial in the United States is currently on hold after a patient fell ill. J & J’s first analysis would begin with 20 infections, in accordance with the protocol for its large-scale trial that will begin on September 21.

AstraZeneca and J&J declined to comment.

(Reporting by Marisa Taylor in Washington and Dan Levine in San Francisco; Editing by Michele Gershberg and Will Dunham)