Pfizer and BioNTech said today that BNT162b2, the lead candidate of their BNT162 COVID-19 vaccine program, aced its Phase III trial by showing itself to be more than 90% effective in preventing COVID-19 in participants without evidence of prior SARS-CoV-2 infection, in the study’s first interim efficacy analysis.

The external, independent Data Monitoring Committee (DMC) of the Phase III trial (NCT04368728) carried out the analysis, which included assessing 94 confirmed cases of COVID-19 among the trial’s 43,538 participants to date—of which 38,955 had already received their second dose of BNT162b2.

Pfizer and BioNTech now estimate that a median of two months of safety data following the second and final dose of the vaccine candidate—the amount of safety data specified by the FDA in its guidance for potential Emergency Use Authorization (EUA)—will be available by the third week of November.

The companies said they plan to file for an EUA for their vaccine “soon after.”

“Today is a great day for science and humanity,” declared Albert Bourla, DVM, PhD, Pfizer Chairman and CEO, in a statement. “The first set of results from our Phase III COVID-19 vaccine trial provides the initial evidence of our vaccine’s ability to prevent COVID-19.”

The trial is continuing to enroll participants, and is expected to continue through a final data analysis, when a total of 164 confirmed COVID-19 cases have accrued, Pfizer and BioNTech said. The evaluation will also assess the potential for the vaccine candidate to provide protection against COVID-19 in those with prior exposure to SARS-CoV-2, as well as vaccine prevention against severe COVID-19 disease.

“We are reaching this critical milestone in our vaccine development program at a time when the world needs it most with infection rates setting new records, hospitals nearing over-capacity and economies struggling to reopen. With today’s news, we are a significant step closer to providing people around the world with a much-needed breakthrough to help bring an end to this global health crisis,” Bourla added.

The companies said they plan to submit Phase III data for publication in a peer-reviewed journal: “We look forward to sharing additional efficacy and safety data generated from thousands of participants in the coming weeks,”

“Very promising”

One analyst this morning echoed Pfizer’s upbeat assessment of the trial’s success.

“This early disclosure looks very promising and we think should beat expectations of most investors and the market, and should provide a welcome boost to sentiment going into an epidemiologically challenging winter season,” Geoffrey C. Porges, MBBS, director of therapeutics research and a senior research analyst with SVB Leerink.

BNT162b2 is a nucleoside modified mRNA (modRNA) candidate that encodes an optimized SARS-CoV-2 full-length spike glycoprotein antigen. It has received the FDA’s Fast Track designation, as has the other advanced construct under study, BNT162b1, another nucleoside modRNA candidate which encodes an optimized SARS-CoV-2 receptor-binding domain (RBD) antigen.

Pfizer and BioNTech are studying BNT162b2, BNT162b1, and two other  constructs of BNT162: a uridine containing mRNA (uRNA) candidate; and a candidate using self-amplifying mRNA (saRNA).

BNT162b2 is among 20 “Front Runner” candidates among the more than 300 COVID-19 therapeutics under study in GEN’s “COVID-19 Drug & Vaccine Candidate Tracker.”

The first interim analysis had initially been planned to take place after the first 32 participants in both vaccine and placebo arms developed COVID-19. Following public criticism that the data from that size of a subpopulation may not provide sufficient data for the large-scale vaccination envisioned for COVID-19. Pfizer and BioNTech opted to drop the 32-case interim analysis and conduct the first interim analysis with at least 62 participants.

By the time the companies concluded talks with the FDA, they said, the number of participants with COVID-19 reached 94, and the data monitoring committee began its analysis on all those cases, Pfizer and BioNTech said.

The Phase III trial began in July as a Phase II/III study of up to 30,000 patients, after the companies switched their lead vaccine candidate from BNT162b1 to BNT162b2, citing stronger clinical data. In September, BioNTech and Pfizer submitted an amended protocol to the FDA seeking approval to add 14,000 participants to their trial.

Of the trial’s 43,538 participants, approximately 42% of global participants and 30% of U.S. participants have racially and ethnically diverse backgrounds, BioNTech and Pfizer said.

Up to 1.3B doses in 2021

Pfizer and BioNTech project that they expect to supply up to 50 million vaccine doses globally this year, and manufacture up to 1.3 billion doses in 2021.

A spokesman for U.K. Prime Minister Boris Johnson today told Reuters that the country has ordered 40 million doses of BNT162b2, with 10 million of those doses expected to be available by the end of this year. BNT162b2 is one of six COVID-19 vaccines for which the U.K. has arranged supply agreements.

In the U.S., the Department of Health and Human Services (HHS) and Department of Defense (DoD) in July ordered an initial 100 million doses of the vaccine for $1.95 billion—which the companies agreed to offer for free under an agreement signed as part of Operation Warp Speed, the Trump administration’s effort to accelerate development of up to 300 million doses of COVID-19 vaccines by January.

Under that agreement, the U.S. federal government has the option to purchase 500 million additional doses.

The companies have not disclosed the price of those additional 500 million doses should Washington agree to order them—but have said their agreement is subject to Pfizer successfully manufacturing and obtaining approval or emergency use authorization for the vaccine.

In addition to the trial’s primary efficacy endpoints evaluating confirmed COVID-19 cases accruing from seven days after the second dose, the final analysis will upon FDA approval include new secondary endpoints evaluating efficacy based on cases accruing 14 days after the second dose as well: “The companies believe that the addition of these secondary endpoints will help align data across all COVID-19 vaccine studies and allow for cross-trial learnings and comparisons between these novel vaccine platforms.”

The announcement touched off a more than 1,600 point (>5%) surge in the Dow Jones Industrial Average at the start of trading, and a >3.5% surge in the S&P 500. As of 9:45 a.m., Pfizer shares rose about 8% in pre-market trading to $39.30, while BioNTech shares jumped nearly 21% to $111.00 a share.

The trial’s DMC had not reported any serious safety concerns and has recommended that the study continues to collect additional safety and efficacy data as planned, Pfizer and BioNTech said.

“The first interim analysis of our global Phase 3 study provides evidence that a vaccine may effectively prevent COVID-19. This is a victory for innovation, science and a global collaborative effort,” stated Prof. Ugur Sahin, BioNTech Co-founder and CEO.

“When we embarked on this journey 10 months ago this is what we aspired to achieve,” Sahin said. “Especially today, while we are all in the midst of a second wave and many of us in lockdown, we appreciate even more how important this milestone is on our path towards ending this pandemic and for all of us to regain a sense of normality.”

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