Moderna Inc.’s phase III win with its COVID-19 vaccine candidate, mRNA-1273, lifted spirits while validating the Cambridge, Mass.-based firm’s platform, as Wall Street buzzed with comparisons between the prospects that have yielded late-stage data thus far.
An mRNA vaccine encoding for a prefusion stabilized form of the Spike protein, Moderna’s player met the statistical criteria prespecified in the study protocol for efficacy in an interim analysis of the study called Cove, with efficacy of 94.5%. Shares of the company (NASDAQ:MRNA) closed Nov. 16 at $97.95, up $8.56, after trading as high as $100.38 on news about findings by the NIH-appointed data safety monitoring board (DSMB). The analysis, Cove’s first, included 95 people with confirmed cases of the virus.
SVB Leerink analyst Mani Foroohar pointed out in a report that Moderna’s 94.5% point estimate landed well above the previously specified primary endpoint of about 74.1%. The rollout follows phase III results from Pfizer Inc., of New York, and Mainz, Germany-based Biontech SE with BNT-162b2, also an mRNA vaccine, with “over 90%” efficacy. “While questions on durability and specifics of safety and tolerability vs. Pfizer/Biontech and other competitors will come into focus looking forward, we expect those issues to take a back seat for the moment and for Moderna shares to trade up materially, as bullish investors read across from this data to the vaccine portfolio as a whole,” Foroohar said. Jefferies analyst Michael Yee said that “it will be interesting to see if other platforms show this high [level] of efficacy.” The final outcomes from Moderna and Pfizer/Biontech “may move around a little bit, but probably not significantly,” he added in a report.
Moderna said the vaccine remains stable at 2° to 8°C (36° to 46°F), the temperature of a standard home or medical refrigerator, for 30 days, an extension from the earlier estimate of about a week, and stays that way at -20° C (-4°F) for up to six months, at refrigerated conditions for up to 30 days, and at room temperature for up to 12 hours – which could provide an important edge. Brookline analyst Leah Rush Cann said in a report that “the updated, more favorable handling requirements give mRNA-1273 an impactful advantage over other potential vaccines that may be close to approval.” Piper Sandler’s Edward Tenthoff agreed, praising the possibility for wider distribution of the Moderna candidate as well as its easier administration.
Moderna plans to submit for an emergency use authorization (EUA) from the FDA in the weeks ahead, and expects the application will be based on the final analysis of 151 cases, with a median follow-up of more than two months. The study enrolled more than 30,000 participants in the U.S. and is being conducted in collaboration with the U.S. NIH and the Biomedical Advanced Research and Development Authority.
But hard times near term
The primary endpoint is based on the analysis of cases confirmed and adjudicated starting two weeks following the second dose of the vaccine. Of the 95 cases, 90 were observed in the placebo group and five in the mRNA-1273 segment, which led to the point estimate of vaccine efficacy of 94.5% (p<0.0001). A secondary endpoint analyzed severe cases of COVID-19 and included 11 of those as defined by the study protocol, all in the placebo group and none in the mRNA-1273 vaccinated group.
In the 95 cases were 15 older adults (ages 65 and up) and 20 participants identifying as being from diverse communities (including 12 Hispanic or Latinx, four Black or African Americans, three Asian Americans and one multiracial).
The interim analysts included a concurrent review of the available safety data by the DSMB, which did not report any significant safety concerns, and a review of solicited adverse events (AEs) showed the vaccine to be generally well-tolerated. Most AEs were described as mild or moderate. Grade 3 (severe) events greater than or equal to 2% in frequency after the first dose included injection site pain (2.7%), and after the second dose included fatigue (9.7%), myalgia (8.9%), arthralgia (5.2%), headache (4.5%), pain (4.1%) and erythema/redness at the injection site (2%). So far, the safety and efficacy profile seems consistent across all groups.
Moderna is working with the CDC, Operation Warp Speed and McKesson Corp., of Irving, Texas, as well as global stakeholders to gear up for distribution of mRNA-1273, if the EUA and similar, global go-aheads come through. By the end of this year, the company aims to have about 20 million doses of mRNA-1273 ready to ship in the U.S., and is still on track to make 500 million to 1 billion doses globally in 2021.
RBC Capital’s Brian Abrahams speculated in a report about the industry implications of the recent clinical victories. “A higher likelihood of vaccine success near-term, in our view, could reaccelerate sales growth for prescription products particularly sensitive to in-person detailing or physician-administration requirements, though [we] might also see a reversal of sales for COVID-19 therapeutics and classes that have benefited from the new environment,” he said. From a societal perspective, though, darkness still looms. “Positive cases are now rising out of control, with the expected pull-throughs on hospitalization rates and deaths predicting devastating mortality (and morbidity) along the way,” he said. “We have increasing confidence [that] things will begin to normalize by mid-2021, but expect this will be at the cost of another 190,000-320,000 COVID-related deaths and 270,000-440,000 total excess deaths in the U.S. – and those numbers assume that some new restrictions are implemented this fall to help curtail the current wave.”