Virus World

Pfizer and BioNTech are under a white-hot spotlight because their vaccine, by design, is likely to be the first to have any efficacy data. The announcement is both good news and bad news. Umer Raffat, a senior managing director at the investment bank Evercore ISI, wrote in an analyst note that the fact that Pfizer hasn’t conducted an interim analysis was “a good thing” because it means that, based on the details of the trial protocol, the vaccine had not failed to prevent more than 77% of Covid cases, the benchmark for success at this early juncture. But it also suggests that cases of Covid are being reported less frequently among participants in the Pfizer study than in the U.S. as a whole. That means that the study is progressing more slowly than Pfizer and its partner, BioNTech, originally expected. In August, Pfizer had thought that the first interim analysis could occur as early as September. Pfizer and BioNTech are under a white-hot spotlight because their Covid-19 vaccine, by design, is likely to be the first to have any efficacy data. But that first analysis will come when there have been a total of only 32 cases of Covid-19 across the company’s entire 42,000-volunteer study. It would be considered to be positive, Pfizer has said, if six or fewer of those 32 cases occurred in the group that received the vaccine, with the rest occurring in the group that received the placebo. The trial is expected to continue until 150 of the volunteers in the study have had Covid-19.

Pfizer CEO Albert Bourla set the goal of having a Covid-19 vaccine ready by October this spring, in what appeared to be a bid both to combat the pandemic and to make a statement about the company’s research prowess. Pfizer is in the midst of spinning off older, slower-growing parts of the company in a merger with Mylan, which will leave Bourla running a firm whose future will depend heavily on its research laboratories and the prospects of its experimental drugs.  The vaccine itself is expected to be a significant but not huge financial opportunity. Analysts at SVB Leerink estimate sales could peak at $3.5 billion in 2021, and then stabilize at $1.4 billion a year. In its third-quarter earnings, also announced Tuesday, Pfizer reported profits of $2.2 billion on sales of $12.1 billion. But the October time frame has put Pfizer squarely in the political maelstrom of the U.S. election, as President Trump repeatedly predicted that a vaccine would be available before Election Day. It has been clear for months that other companies developing Covid-19 vaccines, including Moderna, AstraZeneca, and Johnson & Johnson, had no chance of hitting that mark.

On Oct. 6, the Food and Drug Administration released new guidance on safety data that would be required before it would consider clearing a vaccine through an emergency use authorization, or EUA, its fastest path to making a vaccine available. The agency told drug makers not to file for an EUA until at least half the patients in their studies have been followed for two months. In an Oct. 16 public letter, Bourla confirmed that this would prevent Pfizer from filing for an EUA until the third week of November. At an advisory panel of outside experts the FDA held last week, the agency signaled that it was not certain it would grant an EUA for a vaccine until a sufficient amount of data had been accumulated to more fully understand the safety and efficacy of a vaccine prospect.

The first human trials of a coronavirus vaccine developed by researchers at the University of Oxford will start today in the U.K. Making the announcement at a recent press briefing, U.K. government Health Secretary Matt Hancock pledged £20 million in government funding to support Oxford University’s ChAdOx1 nCoV-19 coronavirus vaccine program, and another £22.5 million to fund Phase II testing of a coronavirus vaccine in development by Imperial College London, which is projected to start human testing in June. The Imperial College London funding will also be used to help prepare for Phase III studies. “We will throw everything we’ve got at developing a vaccine,” Hancock added. “The U.K. is at the forefront of the global effort … and for all of the efforts around the world, two of the leading vaccine developments are taking place here at home, at Oxford and Imperial.”

The start of human testing in the U.K. coincides with Germany’s regulator, the Paul-Ehrlich-Institut, giving German biotech BioNTech and partner Pfizer the green light to start the first coronavirus vaccine clinical trial in the country. “This is the fifth authorized clinical trial worldwide in which a preventive specific COVID-19 vaccine candidate is tested in humans,” the Federal Institute for Vaccines and Biomedicines said. The Phase I/II study will evaluate the BNT162 vaccine program. Clinical trials are also expected to start in the United States upon regulatory approval, which is anticipated shortly, Pfizer said. The first part of the clinical study in Germany will test variants of the vaccine in 200 healthy volunteers aged 18–55 years. The second part of the study will be expanded to include volunteers who are at an increased risk of infection or increased risk of serious COVID-19 disease.

The companies started a large study of a vaccine candidate for Covid-19 aimed at securing approvals — but it’s not the one for which results were released. Pfizer and BioNTech are starting a large study of a vaccine candidate for Covid-19 aimed at securing approvals — but it’s not the one for which results were released earlier this month. The companies always said that they planned to pick from among four different candidates, all of which use a technology called messenger RNA to produce a protein on SARS-CoV-2, the virus that causes Covid-19. The vaccine is designed to lead the immune system to recognize the protein, and, it is hoped, to attack the virus. On July 1, the companies announced results in a preprint publication showing that one vaccine candidate, BNT162b1, prompted an immune response in patients. That vaccine encoded a key portion of the spike protein, which SARS-CoV-2 uses to enter cells. The vaccine being taken forward, BNT162b2, encodes an optimized version of the whole spike protein, which should lead to “more consistent responses across diverse populations and in older adults,” Pfizer said in a statement. Philip Dormitzer, a Pfizer vice president in charge of vaccines, said the selected vaccine appears to generate a stronger response, in part because it includes more of the spike protein. That could mean less variability in how people respond to the vaccine. It also seemed to cause fewer side effects. “It just seemed a bit milder,” Dormitzer said in an interview. “There were fewer reactions to immunization, and that was an important mark in its favor.”

The study, which began today, will recruit about 30,000 healthy volunteers between 18 and 85, randomizing half to get the vaccine and the rest to get placebo. Pfizer will recruit from about 120 sites in countries around the world, including the U.S., Germany, and Brazil. The primary goal is preventing patients from developing Covid-19, and the secondary endpoints include preventing severe cases of the disease and protecting volunteers against asymptomatic infections. The announcement came hours after Moderna began a 30,000-participant trial of its own. Like Pfizer and BioNTech, Moderna’s vaccine uses messenger RNA to compel the body to produce spike proteins, leading to an immune response that will ideally protect subjects from Covid-19. Pfizer and BioNTech said that they are on track to file for regulatory review as early as October, and that they plan to supply up to 100 million doses by the end of 2020 and 1.3 billion doses by the end of 2021.