TrialSite reported on the Novavax Phase 1 clinical trial, managed by contract research organization Nucleus Network, early on in the process. Now the study results have been peer reviewed and published in the New England Journal of Medicine: the results reveal that the investigational product, NVX-CoV2373 produced by Novavax is in fact safe and actually triggers an immune response.
The Vaccine Candidate
A prefusion protein coronavirus vaccine candidate, NVX-CoV2373 is developed based on the company’s proprietary nanoparticle technology—Matrix-M, an adjuvant to bolster the immune reaction while triggering more intense production of neutralizing antibodies. The company, Novavax, has patented its saponin-based Matrix-M adjuvant: they have demonstrated a potent and well-tolerated effect by triggering the entry of antigen-presenting cells to the site of injection while boosting antigen presence in local lymph nodes, which augments immune response, in the process helping the immunized patient to produce more antibodies against the virus.
The Phase 1 clinical trial (NCT04368988) is a randomized, placebo-controlled study designed to evaluate the immunogenicity and safety of vaccine candidate with or without Matrix-M adjuvant in health participants aged 18 to 59. The Australian investigational team offered either the vaccine candidate or placebo to 131 volunteers back in May. A total of 83 participants received the vaccine with adjuvant (agent used to boost response) while 24 received the vaccine and no booster. Finally, 23 participants received a placebo. The participants received a total of two injections.
The protocol called for participants to keep note of any possible symptoms from strong reactions to mild soreness. Moreover, the Australian study volunteers were given tests to determine if they had COVID 35 days post the very first injection.
After 35 days, no serious, unexpected or unusual adverse events were reported. One person reportedly had a mild fever that went on for a day after the second injection. Additionally, a second participant reported a slight fever lasted for about one day post the second injection. A couple volunteers in the vaccine group reported a headache and some fatigue or generally not feeling well for what turned out to be a median of two days or less.
For the most part, after the second injection a majority of the study volunteers didn’t report any issues or if they did so, they were not material—e.g. some soreness from the second shot while eight volunteers reported some joint pain and fatigue.
Vaccine Triggers Immune Response
The vaccine apparently generated an immune response as the study team reported that all of the volunteers receiving the vaccine actually developed neutralizing antibodies once they received their second injection of NVX-CoV2373.
A promising result is the level of antibody response in the 35 volunteers receiving two doses of the vaccine. Apparently the actual levels of neutralizing antibodies were four to six times greater than what would be recorded in a recovered COVID-19 patient. The study team randomly selected 16 volunteers to measure T -cell response and found that NVX-CoV2373 generated T-cell activity. These are a class of immune cells that helps the body fight off an infection.
Benefit of Adjuvant
The study team reported that there was in fact a clear benefit of including the vaccine adjuvant as it apparently bolstered the antibody response as well as evidenced greater value after the second injection on day 21.
Novavax R&D Comment
Dr. Gregory Glenn, president of R&D at Novavax, observed, “Based on the positive Phase 1 results, we have begun multiple Phase 2 clinical trials, from which we expect to collect preliminary efficacy.” He continued, “Novavax is committed to generating the safety, immunogenicity and efficacy data that will support confident usage of the vaccine, both in the U.S. and globally, and the data published today further bolsters our conviction that this is possible.”
Limitations of this Study
Note that this was a small Phase 1 study and additional data from Phase 2 would be required for more confidence in regards to this experimental vaccine. Volunteers were in good health and that won’t be indicative of real world scenarios where in countries such as the United States, many millions will have comorbidities. Moreover, there is a growing concern that although ethnic minorities, such as African Americans and Hispanics are falling ill to COVID-19 at higher rates, they are not participating in the current studies in sufficient amounts. This was the case with the Phase 1 Novavax study that was conducted in Australia.
Back in July, it was announced that Novavax was selected to participate in the U.S. government’s Operation Warp Speed and as part of that deal was awarded $1.6 billion by the government to complete late-stage clinical development including a pivotal Phase 3 study as well as establish production capability and the ability to deliver 100 million doses of the experimental vaccine as early as late 2020.
Since then the company has been very busy inking deals, including:
· A license agreement with the busiest vaccine manufacturer in the world—the Serum Institute of India for distribution in low-and middle-income countries and India.
· The company formed a partnership with FUJIFILM Diosynth Biotechnologies (FDB) to manufacture drug substances in support of production of NVX-CoV2373 at a site in Morrisville, NC.
· The company received a commitment for $384 million by the Coalition for Epidemic Preparedness Innovations (CEPI) back in May.
Publicly traded under the symbol NVAX, the late-stage biotechnology company focuses on the development of drugs and vaccines based on its proprietary recombinant technology platform. They are headquartered in Gaithersburg, MD with facilities in Uppsala, Sweden and Bohumil, Czech Republic.