Pfizer revealed Tuesday that researchers have not yet conducted an analysis of the efficacy of the vaccine it is developing against Covid-19.
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.
Against that backdrop, there is a huge amount of attention on Pfizer’s interim analyses, which were originally designed as a way to make a vaccine available as soon as possible. Such analyses are a standard part of clinical trials, and are conducted by an independent committee called a data and safety monitoring board, or DSMB.
However, it’s unusual that Pfizer will be getting reports from the DSMB on the efficacy of the study as it is still ongoing, and it is also unusual that those results will be announced as the study continues with patients and doctors remaining unaware of who has received the vaccine and who has received placebo. It might also have been possible, for instance, for Pfizer to have told the DSMB only to give it information if there is enough safety data to file for an EUA. That appears to be the approach, for instance, that is being taken by Johnson & Johnson with its Covid-19 vaccine. In many but not all circumstances, interim analyses are made public because a treatment or vaccine is so effective (or ineffective or unsafe) that it is no longer possible to continue a study.
Receiving these reports puts Pfizer in the position of having to disclose them for both financial and ethical reasons. That’s certainly true if the DSMB says the vaccine is effective or definitively not effective, but Pfizer may also feel the need to announce if the DSMB conducts an interim analysis and allows the study to continue.
Bourla said on a conference call Tuesday that he is “cautiously optimistic” that the study will have positive results, and that those could come in an interim analysis. “You never know until you have a study result,” he said. “Let’s all have the patience that is required for something so important for public health.” He later said that he knows that the U.S election is raising the tension around the data readout. “This is not going to be a Republican vaccine or a Democratic vaccine. This is going to be a vaccine for the citizens of the world. I hope that it is going to be effective.”
Making educated guesses about what is happening in a clinical trial is normal practice for investors who follow pharmaceutical companies, but not for a general public that is hoping a vaccine will be able to help slow a pandemic. A warning, then, from past attempts from investors to read the tea leaves on clinical trials: They are frequently wrong.
For instance, on Monday, analysts at Morgan Stanley wrote that they suspected the first interim, which Pfizer said requires 77% vaccine efficacy, had happened in mid-October, and that Pfizer could be getting its second planned report on the data, which occurs after 62 cases of Covid-19 occur in the trial. That was smart speculation — and, it turns out, incorrect.
In an unrelated update, Novavax, another closely watched vaccine maker, said the U.S. study of its Covid-19 vaccine would start in late November, after it was expected.