Novavax COVID-19 vaccine hits 90% efficacy in pivotal U.S. trial

Novavax’s COVID-19 vaccine candidate has achieved 90.4% efficacy in the pivotal trial designed to support U.S. approval. The phase 3 data set Novavax up to file for approval in the third quarter.

The Maryland-based company reported its vaccine achieved 89.3% efficacy in a 15,000-subject U.K. phase 3 clinical trial in January. Data from the PREVENT-19 clinical trial that enrolled 29,960 subjects in Mexico and the U.S. validate the earlier readout and provide further evidence of the efficacy of the recombinant nanoparticle protein-based COVID-19 vaccine against certain variants of concern.

The headline finding is that 63 cases of PCR-confirmed symptomatic COVID-19 occurred at least seven days after the second dose in the one-third of participants who received placebo, compared to 14 cases in the vaccine group. The difference resulted in 90.4% efficacy against the primary endpoint.

Digging deeper, 10 moderate cases and four severe cases happened in the placebo group, whereas all the cases in the vaccine cohort were mild, as defined by the trial protocol. Based on the available data, the NVX-CoV2373 vaccine has 100% efficacy against moderate and severe COVID-19.

Novavax collected efficacy data from Jan. 25 to April 30, a period in which variants of concern and interest were circulating in the U.S. and Mexico. NVX-CoV2373, like other available vaccines, was designed to protect against the original SARS-CoV-2 virus and as such could be less effective against variants that have arisen during the pandemic.

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The study has sequencing data for 54 of the 77 cases. Ten cases involved viruses not considered to be of variants of concern or interest. All those cases happened in the placebo arm. Of the remaining 44 cases, 35 involved variants of concern, primarily the Alpha or B.1.1.7 variant first identified in the U.K., and nine involved variants of interest.

There were 38 cases involving variants in the placebo group and six in the vaccine cohort. The result suggests NVX-CoV2373 is highly effective against variants—Novavax calculated the efficacy at 93.2%—but may mask weaknesses against particular forms of the coronavirus.

The Alpha variant accounted for 63.6% of cases involving variants of concern and interest. As the Alpha variant was prevalent in the U.K. during Novavax’s earlier phase 3 trial, NVX-CoV2373 has already demonstrated a high level of efficacy against that particular form of the coronavirus. Studies suggest other vaccines work against the Alpha variant, too. 

However, other variants have different mutations that may render vaccines less effective. Novavax provided early evidence of the potential for vaccine escape in January when it reported 49.4% efficacy in a 4,400-subject phase 2b in South Africa, where the Beta or B.1.351 variant was common at the time of the study.

Two of the sequenced cases in the U.S.-Mexico trial involved the Beta variant, reflecting the low levels of the virus in the countries during the study. There were two sequenced cases of the Gamma variant, the P.1 virus that originated in Brazil, and three of the Epsilon variant found in California. The dominance of Alpha during the study makes it hard to determine efficacy against other variants.

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The reactogenicity profile is clearer. Novavax linked the vaccine to a higher rate of local reactions, specifically tenderness and pain, after both doses, but the vast majority of reactions were grade one or two, and many patients were free from such side effects, even after the second dose. 

Rates of systemic reactions in the placebo and vaccine arms were comparable after one dose but diverged after the second dose. Reactions such as headache, muscle pain and fatigue were more common in the vaccine group, but no one event affected more than 50% of people and almost all the side effects were grade one or two. 

Novavax is now continuing to gather data on people aged 12 to 18 years while working to prepare to seek approval. In its statement to disclose the data, Novavax reaffirmed its plan to file for approval in the third quarter. Novavax had planned to seek approval on the strength of the U.K. data in the second quarter but was held up by manufacturing issues.

The latest news is that Novavax will file for approval “upon completion of the final phases of process qualification and assay validation needed to meet chemistry, manufacturing and controls requirements.” Novavax expects to be making 100 million doses a month by the end of the third quarter and hit 150 million doses a month by the end of the year.