Enthusiasm stayed high but abated somewhat throughout the day as Wall Street took in the positive interim phase III results from Biontech SE and Pfizer Inc. with the COVID-19 vaccine candidate BNT-162b2.
New York-based Pfizer said no serious safety concerns turned up but provided no details in that regard, and the company noted in a press release that data are still being gathered; efficacy could drop as the study goes on. It’s still unknown how well the vaccine ultimately will work against severe disease among the elderly and infirm. And the profile of BNT-162b2 in tackling any new COVID-19 strains that might arise is unknown pending further research.
As the 43,538-subject, phase III experiment goes on with the product, which encodes an optimized SARS-CoV-2 full-length spike glycoprotein, Pfizer reported that BNT-162b2 gained 90% efficacy in preventing infection at the first interim analysis conducted by an independent data monitoring committee (DMC).
Shares of Mainz, Germany-based Biontech (NASDAQ:BNTX) closed at $104.80, up $12.80, having traded as high as $115. Pfizer (NYSE:PFE) ended at $39.20, up $2.80, or 7.7%, after rising to $41.99 during the day.
After talks with the FDA, the companies decided to drop the 32-case interim analysis plan and instead let the DMC do its first peek at a minimum of 62. The analysis ended up evaluating 94 confirmed cases of COVID-19. Between vaccinated individuals and those who received the placebo, the case split indicates a vaccine efficacy rate above 90% at seven days after the second dose, so protection is achieved 28 days after the start of the two-dose schedule. The DMC said the study should continue. Biontech and Pfizer said they will discuss the findings thus far with regulatory authorities worldwide.
Begun this summer, the study had given the second dose to 38.955 participants as of Nov. 8. Among those in the U.S., 30% show racially and ethnically diverse backgrounds. Globally, the number was 42% diverse, though details were not provided on that, either. The trial will keep going through the final analysis, when a total of 164 confirmed COVID-19 cases have accrued.
Along with the primary efficacy endpoints in confirmed COVID-19 cases that accrue from seven days after the second dose, the final analysis will include, with the FDA’s blessing, new secondary efficacy endpoints based on cases accruing 14 days after the second dose. The altered protocol should help line up data across all COVID-19 vaccine studies, which would allow for informative comparisons. Participants will be monitored for two years after their dosing is completed.
$8.5B in first-year sales
Cowen analyst Steve Scala said in a report that the BNT-162b2 outcome is “about as good a result as could be hoped [for], at this stage. Notably, the interim analysis included more than half of the events needed for the final analysis, lending greater confidence that the greater than 90% efficacy will hold relatively steady. Signs of antibody-dependent enhancement would potentially have emerged by now,” he said, noting that “we are not out of the woods on safety, but are at least headed in the right direction.” The outcome “also greatly increases the likelihood that competitor vaccine candidates will be successful – wonderful news for society.”
The phase III findings set a high bar for Moderna Inc. with its COVID-19 vaccine candidate, which bears a similar mechanism of action and is due for interim data this month, a timeline that the Cambridge, Mass.-based company should be able to follow, given the jump in virus cases. SVB Leerink’s Mani Foroohar said in a report that he expected Moderna shares “to be up materially today, with this positive read-across,” though he deemed the Moderna risk-reward profile as “skewed to the downside,” given the “excellent” progress by Pfizer and Biontech. Shares of Moderna (NASDAQ:MRNA) closed at $77.74, up $5.29. During its earnings tally last month, Moderna said the phase III study with mRNA-1273 is fully enrolled with 30,000 participants, including 37% from diverse communities and 42% at high risk of severe disease. The study began in late July.
With BNT-162b2, Pfizer said a median of two months of safety data following the second (final) dose – which is what the FDA needs for potential emergency use authorization (EUA) – will be available by the third week of this month. Biontech and Pfizer are putting together safety data related to manufacturing. They expect to crank out globally up to 50 million vaccine doses in 2020 and up to 1.3 billion doses in 2021.
During Pfizer’s earnings call in late October, CEO Albert Bourla talked about the supply details. “We have a contract with the U.S. government that we should provide them 100 million doses by March, and we are feeling very good about our ability to do it,” he said. “But also there's a provision that we should provide 40 million doses this year. Just to put things into perspective, let's say, 30 million doses – it’s 15 million people,” which, he acknowledged, “is a very small part of the population. So [the vaccine is] not going to be massively available, it’s going to be targeted in its availability. As we move into the first months of 2021, we are going to have much more massive distribution of the vaccine around the world.”
Evercore ISI’s Josh Schimmer pointed out that mRNA vaccines take longer to scale, whereas subunit adjuvant ones, such as Gaithersburg, Md.-based Novavax Inc. is developing, and viral vector vaccines, such as Astrazeneca plc has in the hopper, scale much faster. “If we get the right mix of approved vaccines, we could have adequate supply for the U.S. and well beyond by the first quarter of 2021, but if we’re only relying on mRNA vaccines, we might not have adequate supply until the third quarter of that year. Fortunately, enough of the vaccines should work reasonably well to put us on a mid-first half of 2021 supply timeline,” in his view. In late-stage development with fast-track status is Novavax’s NVXCoV2373, described as a stable, prefusion protein made using the firm’s nanoparticle technology, including its MatrixM adjuvant.
SVB Leerink analyst Geoffrey Porges said in a report that the phase III BNT-162b2 outcome so far “looks very promising” and “should beat expectations of most investors and the market,” as well as provide “a welcome boost to sentiment going into an epidemiologically challenging winter season.” Mizuho’s Vamil Divan cheered, too, predicting the EUA by December, and pegging sales at more than $8.5 billion in the first year.
Trouble cited in MAb space
J.P. Morgan analyst Cory Kasimov said the Pfizer/Biontech rollout “signals that a return to normalcy could be possible in the not-too-distant future,” though he nodded to the shortage of data beyond the top line. Because of “the competitive nature of COVID-19 vaccines (there could be many) and the uncertain duration of the pandemic, we believe that the market is already ascribing a substantial amount of value” to them, which leaves Kasimov “cautious on the ultimate opportunity (on a per company level), despite the obvious importance BNT-162b2 will have in controlling the pandemic in the near to intermediate term.” Data from the full phase III study will be submitted to a scientific journal, Pfizer said.
As developers push ahead with would-be vaccines and therapies, the COVID-19 treatment space becomes more complicated. Safety has arisen as a potential concern for monoclonal antibodies used on hospitalized patients. Tarrytown, N.Y.-based Regeneron Pharmaceuticals Inc., with REGN-COV2, paused recruitment of high-flow oxygen and mechanical ventilator patients. Eli Lilly and Co., of Indianapolis, stopped its study with bamlanivimab (LY-CoV555) outright. Regeneron’s Recovery trial has continued to recruit, although this did little to quell the worries of such analysts as Baird’s Madhu Kumar, who covers San Francisco-based Vir Biotechnology Inc., with VIR-7831, which binds to an epitope on SARS-CoV-2 that is shared with SARS-CoV-1, indicating that the epitope is highly conserved, which may make it more difficult for resistance to build, the company said.
Hints of the cause of the Regeneron and Lilly difficulties surfaced recently in London-based Astrazeneca’s earnings call, when Menelas Pangalos, vice president of R&D, told investors that the “Fc inactivation that we've done [with our candidate] we think is important – potentially could be important – in those severe patients. As you know, Lilly and Regeneron antibodies have both stopped because of a poor risk-benefit in the more severe population." This was news to some, and exact reasons weren’t given, but a June paper in Nature Reviews Immunology suggested that antibody-dependent cellular phagocytosis from COVID-19 monoclonal antibodies might be driven by activation of macrophages. Vir, though, has published plenty of its own favorable research regarding VIR-7831.