CDC recommends Novavax’s Covid shots as mix-and-match first booster to Pfizer or Moderna

There’s a fourth COVID-19 vaccine option in US: Novavax. The availability of the Novavax COVID-19 vaccine offers another option for people who may have been hesitant about getting vaccinated. Novavax’s shots rely on more conventional technology used in other vaccines for decades rather than the newer messenger RNA platform used by Pfizer and Moderna.

The Centers for Disease Control and Prevention on October 19, 2022, recommended Novavax’s Covid boosters for adults in the U.S., including for people who received Pfizer, Moderna or Johnson & Johnson’s shots as their primary series.

The Food and Drug Administration, in a factsheet for healthcare providers, said adults ages 18 and older can receive Novavax as their third dose six months after completion of the primary series of a U.S. authorized Covid vaccine.

The CDC gave the final go ahead for pharmacies to start administering the Novavax boosters just hours after the FDA had authorized the shots. Dr. Evelyn Twentyman, a CDC official, announced the Novavax recommendation during a meeting of the agency’s independent vaccine experts Wednesday afternoon.

The CDC recommended Novavax’s boosters without a debate or vote from its independent experts.

The authorization of Novavax’s booster could significantly increase the role that its shot plays in U.S. vaccination efforts. Up until now, Novavax’s vaccine was only authorized as a two-dose primary series, which limited its market because so many people were already immunized with Pfizer or Moderna. Tens of thousands of people have been immunized against Covid with Novavax’s shots compared with more than 200 million who’ve received other vaccines in the U.S.

The company’s shares jumped by almost 6% in morning trading but were flat by noon.

The FDA’s decision to allow people who received two doses of Pfizer or Moderna to receive Novavax as their third shot means millions of more people can get the Maryland biotech company’s vaccine.

“According to CDC data, almost 50 percent of adults who received their primary series have yet to receive their first booster dose. Offering another vaccine choice may help increase COVID-19 booster vaccination rates for these adults,” Novavax CEO Stanley Erck said in a statement Wednesday.

Only 35,300 people have received Novavax’s shots as a primary series so far in the U.S., according to data from the CDC. By comparison, some 372.5 million Pfizer shots, 235.8 million Moderna doses and 18.9 million Johnson & Johnson shots have been administered across the U.S. so far.

But allowing for mix and matching opens Novavax’s market up to roughly the 100 million adults in the US who have completed their primary series but not received a first booster dose.

The FDA’s authorization of Novavax’s boosters comes as millions of Americans have already received Pfizer’s and Moderna’s new bivalent shots that target the dominant omicron BA.5 subvariant and the original strain of Covid that first emerged in Wuhan, China in 2019.

U.S. health officials believe Pfizer and Moderna’s updated boosters will provide stronger protection against infection and disease this winter than the first generation of vaccines because they target omicron BA.5, which is causing most infections right now.

Novavax’s newly authorized booster was developed against the original strain of Covid but the company believes its protein technology provides durable protection across different variants of the virus. Novavax’s shots rely on more conventional technology used in other vaccines for decades rather than the newer messenger RNA platform used by Pfizer and Moderna.

Novavax said its booster doses triggered robust antibodies against omicron BA.1, BA.2 and the dominant BA.5 subvariant in studies that observed adults who received the third shot 8 to 11 months after receiving their Novavax primary series.

The booster dose also induced an immune response in participants who received Moderna, Pfizer and Johnson & Johnson as their primary series, according to the company.

Dr. Filip Dubovsky, Novavax’s chief medical officer, said the company believes its shots will provide durable protection even as the virus continues to evolve.

“We think we have a product that has a broad immune response, so we’re not going to be chasing the virus each time a new a new variant crops up. That needs to be proven but that’s our hypothesis,” Dubovsky said.

The most common side effects of Novavax’s vaccine are pain at the injection site, fatigue, headache, muscle pain, nausea and vomiting, according to the Centers for Disease Control and Prevention.

The FDA, in a fact sheet for health-care providers, has warned that Novavax’s primary series appears to carry a risk of heart inflammation called myocarditis. Pfizer’s and Moderna’s shots also carry an elevated risk of myocarditis primarily in young men and adolescent boys after the second dose.

A study from the CDC last spring found that Covid infection carries a higher risk of myocarditis than Pfizer or Moderna vaccination.

Novavax has not presented real-world efficacy data on how its shots perform against BA.5, one of the most immune evasive variants of Covid yet. Pfizer and Moderna also do not have real-world data on how their new boosters perform against BA.5.

Novavax was one of the original participants in the U.S. race to develop a vaccine in 2020 and received $1.8 billion in taxpayer money, but fell behind Pfizer and Moderna because it had difficulties getting its manufacturing in place.

The FDA authorized Novavax’s two-dose primary series over the summer in the hope that people who are skeptical of Pfizer’s and Moderna’s shots would be more willing to get immunized with the Novavax version. People ages 12 and older are eligible for Novavax’s primary series, while people 18 and over can now get its booster shot.

People who received Novavax’s vaccine as their primary series are also eligible for Pfizer and BioNTech’s or Moderna’s new omicron booster.

PREVENT-19 adult and adolescent homologous boosting

In the PREVENT-19 trial, a single homologous booster dose was given to select adult participants aged 18 and older, approximately eight or 11 months after their primary series. Following a booster dose, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike (anti-S) Immunoglobulin G (IgG; a type of antibody) levels increased significantly relative to pre-boost levels, rising above the level correlated with 95% vaccine efficacy in a recent USG study. Neutralizing antibodies against the prototype strain also increased by 34- to 27-fold compared to pre-boost levels when boosted at eight or 11 months. Boosting also increased IgG and human angiotensin converting enzyme 2 (hACE2) receptor inhibition antibody levels against Omicron BA.1, BA.2, and BA.5 variants, with levels that are comparable to those observed in Phase 3 efficacy studies.

In the pediatric expansion of PREVENT-19 which evaluated boosting in adolescents aged 12 through 17, a single homologous booster dose was evaluated for anti-S IgG, hACE2 receptor inhibition and neutralization antibody responses. Following boosting, neutralizing titers were 2.7-fold higher than those seen with primary vaccination, and a significant boost was observed for antibody against Omicron BA.1, BA.2, and BA.5.

In both adults and adolescents, a third dose of the Novavax COVID-19 vaccine decreased the antigenic distance between SARS-CoV-2 variant and prototype virus strains, suggesting benefit for the prevention of COVID-19 against contemporary variants such as Omicron. Additionally, in both adults and adolescents, booster doses were well tolerated, with mostly mild to moderate reactogenicity that was of short duration.

About PREVENT-19

PREVENT-19 (the PRE-fusion protein subunit Vaccine Efficacy Novavax Trial | COVID-19) is a 2:1 randomized, placebo-controlled, observer-blinded trial to evaluate the efficacy, safety, and immunogenicity of NVX-CoV2373 with Matrix-M adjuvant in 29,960 participants 18 years of age and over in 119 locations in the U.S. and Mexico. The primary endpoint for PREVENT-19 was the first occurrence of PCR-confirmed symptomatic (mild, moderate, or severe) COVID-19 with onset at least seven days after the second dose in serologically negative (to SARS-CoV-2) adult participants at baseline. The statistical success criterion included a lower bound of 95% CI >30%. A secondary endpoint was the prevention of PCR-confirmed, symptomatic moderate or severe COVID-19. Both endpoints were assessed at least seven days after the second study vaccination in volunteers who had not been previously infected with SARS-CoV-2. In the trial, NVX-CoV2373 achieved 90.4% efficacy overall. It was generally well-tolerated and elicited a robust antibody response after the second dose in both studies. Full results of the trial were published in the New England Journal of Medicine.

The pediatric expansion of PREVENT-19 is a 2:1 randomized, placebo-controlled, observer-blinded trial to evaluate the safety, effectiveness, and efficacy of NVX-CoV2373 with Matrix-M adjuvant in 2,247 adolescent participants 12 to 17 years of age in 73 locations in the U.S., compared with placebo. In the pediatric trial, the vaccine achieved its primary effectiveness endpoint (non-inferiority of the neutralizing antibody response compared to young adult participants 18 through 25 years of age from PREVENT-19) and demonstrated 80% efficacy overall at a time when the Delta variant of concern was the predominant circulating strain in the U.S. Additionally, immune responses were about two-to-three-fold higher in adolescents than in adults against all variants studied.

About the Novavax COVID-19 vaccine (NVX-CoV2373)

The Novavax COVID-19 vaccine (NVX-CoV2373) is a protein-based vaccine engineered from the genetic sequence of the first strain of SARS-CoV-2, the virus that causes COVID-19 disease. The vaccine was created using Novavax' recombinant nanoparticle technology to generate antigen derived from the coronavirus spike (S) protein and is formulated with Novavax' patented saponin-based Matrix-M™ adjuvant to enhance the immune response and stimulate high levels of neutralizing antibodies. The Novavax COVID-19 vaccine contains purified protein antigen and can neither replicate, nor can it cause COVID-19.

The vaccine is packaged as a ready-to-use liquid formulation in a vial containing ten doses. The vaccination regimen calls for two 0.5 ml doses (5 mcg antigen and 50 mcg Matrix-M adjuvant) given intramuscularly 21 days apart. The vaccine is stored at 2°- 8° Celsius, enabling the use of existing vaccine supply and cold chain channels. Use of the vaccine should be in accordance with official recommendations.

Novavax has established partnerships for the manufacture, commercialization, and distribution of the vaccine worldwide. Existing authorizations leverage Novavax' manufacturing partnership with Serum Institute of India, the world's largest vaccine manufacturer by volume. They will later be supplemented with data from additional manufacturing sites throughout Novavax' global supply chain.

About Matrix-M™ Adjuvant

Novavax' patented saponin-based Matrix-M adjuvant has demonstrated a potent and well-tolerated effect by stimulating the entry of antigen-presenting cells into the injection site and enhancing antigen presentation in local lymph nodes, boosting immune response.

About Novavax

Novavax, Inc. (Nasdaq: NVAX.O) is a biotechnology company that promotes improved health globally through the discovery, development, and commercialization of innovative vaccines to prevent serious infectious diseases. The company's proprietary recombinant technology platform harnesses the power and speed of genetic engineering to efficiently produce highly immunogenic nanoparticles designed to address urgent global health needs. The Novavax COVID-19 vaccine has received authorization from multiple regulatory authorities globally, including the U.S. Food and Drug Administration, the European Commission, and the World Health Organization. The vaccine is currently under review by multiple regulatory agencies worldwide, including for additional populations and indications such as adolescents and as a booster. In addition to its COVID-19 vaccine, Novavax is also currently evaluating its COVID-19-Influenza Combination vaccine candidate in a Phase 1/2 clinical trial, its quadrivalent influenza investigational vaccine candidate, and an Omicron strain-based vaccine (NVX-CoV2515) as well as a bivalent format Omicron-based / original strain-based vaccine. These vaccine candidates incorporate Novavax' proprietary saponin-based Matrix-M adjuvant to enhance the immune response and stimulate high levels of neutralizing antibodies.

Novavax, Inc., presented data on Oct 12, 2022 from the Phase 3 PREVENT-19 trial and Study 307 (Lot Consistency) at the World Vaccine Congress Europe 2022. PREVENT-19 data in both adults aged 18 and older and adolescents aged 12 through 17 showed the prototype Novavax COVID-19 vaccine (NVX-CoV2373) achieved its pre-specified immunologic endpoint. Study 307 (Lot Consistency) met its primary endpoint, showing that three lots of the Novavax COVID-19 vaccine tested as a heterologous booster induced consistent immune responses in previously vaccinated adults aged 18 to 49.

It’s not new technology

“This vaccine contains harmless spike protein subunits with an adjuvant added to boost immune response. And, unlike mRNA vaccines, protein-based vaccines do not contain any genetic material,” said Dr. Fryhofer. “Our vast experience with protein subunit vaccines should be reassuring to those who worry about the newness of mRNA vaccine technology.”

“This protein-based platform is new for COVID vaccines but it's not really new. This technology has been around for more than 30 years,” she said, noting “it’s already been used in making other vaccines, for example, for flu, hepatitis B and whooping cough.”

Expect typical side effects

“Just like the mRNA vaccines, these vaccines are reactogenic, so expect fatigue, muscle pain, joint pain, headache, maybe some nausea, vomiting, maybe a little fever,” said Dr. Fryhofer. “These side effects usually go away within one to two days.”

“Unfortunately, as we've seen with the mRNA vaccines, there have been reports of myocarditis and pericarditis after Novavax during the clinical trials and also in early post-authorization data,” she said. “We know that the risk of heart complications is higher after COVID disease than after mRNA COVID vaccination among males and females of all ages.

“However, we can't directly compare myocarditis rates between Novavax and mRNA vaccines based on currently available data,” Dr. Fryhofer added. “Now, in the Novavax clinical safety study, there were only four to six cases identified out of more than 40,000 vaccine recipients. “As of the beginning of May of 2022, nearly 750,000 doses of Novavax had been administered in other countries and global post-marketing safety data have revealed 36 cases of myocarditis or pericarditis.”

“Myocarditis risk was addressed by the FDA in its guidance fact sheets, and FDA explains the chance of myocarditis is very low, but it can occur usually within 10 days following vaccination,” she explained. “It also says patients who have chest pain, shortness of breath, the fast heartbeat, heart fluttering or a pounding heart should seek medical care right away.”

“Post-authorization safety monitoring will continue and will be so important in further defining myocarditis risk,” Dr. Fryhofer noted.

Novavax is easy to store and use

“It comes in 10-dose vials, and it's preservative free. A dose is half a cc and contains 5 micrograms of protein subunit antigen along with 50 micrograms of a proprietary adjuvant Matrix-M, which boosts the immune response,” said Dr. Fryhofer, adding it is given “intramuscularly in the deltoid muscle.”

“Novavax has several logistical advantages. It's easy to store, easy to prepare and easy to administer,” she said. “You store it at regular refrigerator temperatures but don't freeze it. No dilutions necessary, but vaccine has to be discarded if it's not used within six hours after the first puncture of the vial.”

You can wait longer between doses

“In the study, vaccine doses were administered three weeks apart. However, CDC guidance says you can extend the interval between doses to as long as eight weeks,” said Dr. Fryhofer. “This extended interval guidance is based on data from mRNA vaccines. There are no specific data on extended intervals for Novavax and this is all based on the mRNA vaccine studies.”

“Some studies of mRNA vaccines have indicated a lower risk of myocarditis and greater immune response with that extended interval,” she said. “The eight-week interval could be considered, especially in young adult males, to reduce potential for myocarditis and at the same time optimize vaccine effectiveness.

“This extended interval recommendation does not apply to those with immunocompromised conditions,” Dr. Fryhofer added. “CDC recommends sticking to that three-week interval for patients with immunocompromised conditions so we can get their immune protection built up as quickly as possible.”

Be mindful of vaccine co-administration

There’s some “good news” about coadministration of flu and COVID-19 vaccines, said Dr. Fryhofer. “It's fine to give flu shots and COVID vaccines at the same time, and that also goes for the Novavax vaccine.

“Also, there's no problem giving Novavax or any of the other COVID vaccines with other vaccines with one exception: orthopoxvirus vaccines,” she added, noting that while “we're in the middle of a monkeypox outbreak … ACAM2000 and JYNNEOS are the two vaccines available for orthopoxvirus viruses.”

Unfortunately, “ACAM2000 has been linked to myocarditis. We don't know if there's an increased risk of myocarditis with JYNNEOS yet, but if you've received a dose of one of these orthopox vaccines, CDC suggests waiting four weeks to get a COVID vaccine dose,” Dr. Fryhofer explained. “However, if you've already received a COVID vaccine and you're now at risk of monkeypox due to exposure, no need to wait. Go ahead and get the monkeypox vaccine dose now.

“And remember, Novavax and other COVID vaccines are reactogenic and can have significant side effects,” she said. “The shingles vaccine—Shingrix—also is very reactogenic, so you might want to think twice about getting both shingles vaccine and COVID vaccine on the same day.”