With strong results in hand from the phase I stage of its phase I/II study testing a would-be COVID-19 subunit vaccine, Novavax Inc.’s president of R&D, Gregory Glenn, said “it’s possible we could go down in the dose” as work proceeds and get similar efficacy. But even without the as-yet-unproven opportunity of dose sparing, the outcome was impressive from the trial that evaluated NVX-CoV2373 in a randomized, observer-blinded, placebo-controlled experiment with and without the company’s Matrix‑M adjuvant in healthy adults ages 18 to 59.
Shares (NASDAQ:NVAX) closed Aug. 5 at $173.49, up $16.32, or 10%, after trading as high as $189.40.
The news also favored next-generation adjuvant firm Dynavax Technologies Corp., of Emeryville, Calif., which has gained approval already of Heplisav-B, the adult hepatitis B vaccine deploying Toll-like receptor agonist CpG 1018. Heplisav-B’s approval in late 2017 validated the safety profile. Dynavax partner Clover Biopharmaceuticals Inc., of Chengdu, China, is due to roll out phase I data with its COVID-19 vaccine candidate, SCB-2019, shortly. The product uses London-based Glaxosmithkline’s pandemic adjuvant system as well as the TLR adjuvant from Dynavax, shares of which (NASDAQ:DVAX) closed Aug. 5 at $8.99, down 2 cents, after rising earlier in the day to $9.69
Adjuvanted with Matrix-M, Novavax’s NVX-CoV2373 proved generally well-tolerated and sparked robust antibody responses numerically superior to those seen in human convalescent sera (HCS), the Gaithersburg, Md.-based company said. The data have been submitted for peer review to a scientific journal and to an online preprint server.
Reactogenicity events turned up mild. After the first dose, tenderness and pain were the most frequent local symptoms and systemic events were individually less frequent, with headache, fatigue and myalgia being reported most commonly. After the second dose, as expected, the effect was greater, though most symptoms were reported as grade 1 or less. The average duration of events was less than two days. Unsolicited adverse events (AEs) were collected through 28 days after the second dose, and none classed as severe (grade 3) was found; most were mild and deemed unrelated to the shot. No serious AEs appeared, and safety follow-up continues.
It worked, too. NVX-CoV2373 activated neutralization titers in every subject. The 5-µg adjuvanted dose’s group peak geometric mean titer was 3,906 (95% CI: 2,556; 5,970). All participants developed anti-spike IgG antibodies after a single dose, with many also generating wild-type virus neutralizing antibody (nAb) responses. After the second dose, all subjects had wild-type responses. Levels of anti-spike IgG and viral neutralization compared favorably to responses from patients with clinically significant COVID‑19 disease, Novavax said, and were “highly correlated” with neutralization titers, which means a significant proportion of antibodies were functional.
The Matrix-M adjuvant brought encouraging, polyfunctional CD4+ T-cell responses, and the lower 5-µg dose of NVX‑CoV2373 performed comparably with the 25-µg dose. Cellular immune responses were measured in a subset of participants, where the vaccine caused antigen-specific polyfunctional CD4+ T-cell responses with a strong bias toward the Th1 phenotype (IFN-g, IL-2 and TNF-a). “We're still at the maximum dose that the immune response can be achieved with this vaccine and formulation,” Glenn told investors during a conference call, adding that the firm is following a speedy trajectory.
Evercore ISI analyst Josh Schimmer agreed, calling Novavax “a very fast horse” that delivered neutralization titer levels “well above” what other companies have reported. “This is an exciting update, but one in a series of steps for COVID-19 vaccines and for the broader vaccine field,” he wrote in a report. “Most important is that we have a number of attractive options with different profiles to assess in phase III.”
Cross-trial comparisons are hard to make at the moment, “as illustrated by differences in convalescent plasma nAbs,” Schimmer noted. “This may reflect the types of convalescent patients assessed (or when they were measured), but could also represent assay differences. If we use the absolute neutralizing antibody levels, Novavax is a clear winner.” On the other hand, checking out “multiples of convalescent sera” gives the company “a less perceptible advantage,” in his view. “Notably, Novavax had more severe patients in their convalescent samples.”
J.P. Morgan analyst Eric Joseph liked the Novavax story, too, with a similar caveat. “While we’d still caution against reading too concretely across the various vaccine datasets, we believe it’s not too far a stretch to conclude the nAb activity of NVX-CoV2373 looks best-in-class, particularly when anchored to one of the more (if not most) stringent HCS cohorts” offered by aspirants thus far, he wrote in a report. “With NVX-CoV2373 looking every bit the contender in phase I, we believe relative valuations favor Novavax over the near-term, ahead of the first of the competitor phase III vaccine efficacy readouts.”
Perhaps most enthusiastic was Wainwright’s Vernon Bernardino, who trumpeted in his report that a “definable, sustainable commercial [COVID-19] vaccine opportunity has emerged” from Novavax. He maintained his buy rating and hiked the price target to $132 from $101. The selection of NVX-CoV2373 for the feds’ Operation Warp Speed program “remains underappreciated,” he said.
COVID-19 players continue to jostle for position, readying for hoped-for launches. New Brunswick, N.J.-based Johnson & Johnson inked a deal worth $1 billion-plus with the government for domestic manufacturing and delivery in the U.S. of 100 million doses of its Janssen unit’s prospect, Ad26.COV2.S, for use after approval or emergency use authorization. Pfizer Inc., of New York, and Mainz, Germany-based Biontech SE disclosed a pact with Canada’s government to supply their BNT-162 mRNA-based candidate, assuming clinical success and clearance by Health Canada. The parties didn’t disclose financial details of the deal, which is based on the timing of delivery and the volume of doses.