Novavax, Johnson & Johnson Report COVID-19 Vaccine Data

Recent data releases from Novavax and Johnson & Johnson on coronavirus disease 2019 (COVID-19) vaccines show efficacy, but there remains some concern over new variants that have recently become more prevalent.

Protein-based coronavirus 2019 (COVID-19) vaccine candidate NVX-CoV2373, from Novavax, has reported phase 3 findings showing 89.3% efficacy in prevention of COVID-19 in participants from the UK.

The trial findings—conducted at a time of significant transmission in the country and an emerging, more transmissible variant spreading globally—coincide with phase 2b findings which show lesser prevention of the variant originally observed in South Africa.

The Vaccine

NVX-CoV2373 is a vaccine comprised of a full-length, prefusion spike protein made of proprietary recombinant nanoparticle technology and the saponin-based Matrix-M adjuvant.

Produced in insect cells, the purified protein is encoded by the SARS-CoV-2 spike protein genetic sequence.

With the emergence of new mutated strains of SARS-CoV-2 in regions including southeast England and South Africa, Novavax has begun development of new vaccine constructs specified to the strains’ genetic codes, with expectation that ideal candidates provided via booster or in combination as a bivalent vaccine will become apparent in the coming days.

Testing for these newer vaccines would launch in the second quarter of 2021.

“A primary benefit of our adjuvanted platform is that it uses a very small amount of antigen, enabling the rapid creation and large-scale production of combination vaccine candidates that could potentially address multiple circulating strains of COVID-19,” said Gregory M. Glenn, MD, Novavax president of Research and Development, in a statement.

UK Trial

Investigators enrolled 15,000-plus adult participants aged 18-84 years old, to assess the vaccine for a primary endpoint of occurrence of PCR-confirmed, symptomatic COVID-19 with onset at least 7 days following the booster vaccine dose in participants serologically negative for SARS-CoV-2 at baseline.

More than one-fourth (27%) of trial participants were older than 65 years.

In the first interim analysis of 62 COVID-19 cases, 56 (89.2%) were observed in the placebo arm, versus just 6 in the vaccine group (95% CI, 75.2 – 95.4). Of the 62 cases, just 1 was severe—from a placebo patient.

The highly transmissible UK variant strain was detected in more than half of all observed cases, investigators noted (n = 32). In a post hoc assessment, investigators reported that NVX-CoV2373 was 95.6% efficacious against the original COVID-19 strain, and 85.6% efficacious versus the UK variant strain.

In an interim analysis of the safety database, investigators observed low, balanced rates of severe and medically-attended adverse events in both treatment arms.

Clive Dix, Chair, of the UK Vaccine Taskforce, praised the results as “spectacular,” and expressed encouragement for the slightly less efficacious effect observed against the UK variant with the vaccine.

“This is an incredible achievement that will ensure we can protect individuals in the UK and the rest of the world from this virus,” Dix said in a statement. “Novavax expects to share further details of the UK trial results as additional data become available.”

South Africa Trial

In the phase 2b clinical trial assessing the vaccine versus placebo in 4400-plus adult participants from August 2020 to mid-January 2021, investigators reported a 60% efficacy (95% CI, 19.9 – 80.1) in prevention of COVID-19 among participants who were HIV-negative.

Overall, they observed 29 cases in the placebo group, and 15 in the NVX-CoV2373 group. Again, only 1 severe case was reported in the placebo group.

In the overall trial population, comprised of both HIV-positive and HIV-negative participants, investigators reported a 49.4% efficacy (95% CI, 6.1 – 72.8).

Preliminary sequencing data show that, for 27 of the observed 44 total COVID-19 diagnosis, 92.6% of cases were the South Africa variant.

Investigators stressed, however, that one-third of enrolled participants were seropositive, demonstrating prior COVID-19 infection at baseline. Pre-trial infections, per temporal epidemiology data for the assessed region, indicate these cases would be the original COVID-19 strain.

Whether the current Novavax product could completely protect against the globally-spreading South Africa variant is questionable, yet investigators stress its value in reducing COVID-19 severity.

“The 60% reduced risk against COVID-19 illness in vaccinated individuals in South Africans underscores the value of this vaccine to prevent illness from the highly worrisome variant currently circulating in South Africa, and which is spreading globally,” principal investigator professor Shabir Maddi, executive director of the Vaccines and Infectious Diseases Analytics Research Unit (VIDA) at Wits, said in a statement. “This is the first COVID-19 vaccine for which we now have objective evidence that it protects against the variant dominating in South Africa.”

US Trial

According to Novavax, the enrolling PREVENT-19 clinical trial in US and Mexico has already randomized more than 16,000 participants, with expectation of 30,000 targeted enrollment by early February.

Conducted in support from federal agencies including Operation Warp Speed (OWS), the phase 3, randomized, placebo-controlled, observer-blinded assessment will gauge the efficacy, safety, and immunogenicity of NVX-CoV2373 with Matrix-M in adults versus placebo.

Johnson & Johnson

Johnson & Johnson (J&J) announced today its JNJ-78436735 COVID-19 vaccine was 85 percent effective in preventing severe disease across all regions studied—28 days after vaccination.

These regions included the US, Latin America, and South Africa. Efficacy against severe disease increased over time with no cases in vaccinated participants reported after day 49 in all adults 18 years and older.

Additionally, the vaccine's level of protection against moderate to severe COVID-19 infection was 72% in the United States, 66% in Latin America, and 57% in South Africa—28 days post-vaccination.

The single dose investigational vaccine, which is being developed by the Janssen Pharmaceutical Companies of Johnson & Johnson, is more commonly referred to as the Ad26.COV2.S vaccine, and is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike (S) protein.

“These topline results with a single-shot COVID-19 vaccine candidate represent a promising moment. The potential to significantly reduce the burden of severe disease, by providing an effective and well-tolerated vaccine with just one immunization, is a critical component of the global public health response,” Johnson & Johnson Vice Chairman of the Executive Committee and Chief Scientific Officer Paul Stoffels, MD, said. “A one-shot vaccine is considered by the World Health Organization to be the best option in pandemic settings, enhancing access, distribution and compliance. Eighty-five percent efficacy in preventing severe COVID-19 disease and prevention of COVID-19-related medical interventions will potentially protect hundreds of millions of people from serious and fatal outcomes of COVID-19. It also offers the hope of helping ease the huge burden placed on healthcare systems and communities.”

These results come from the company’s Ensemble study being conducted in eight countries and three regions.

“The J&J vaccine turns in a fantastic result,” former FDA Commissioner Scott Gottlieb, MD. tweeted this morning. “We now have 3 highly effective vaccines. This vaccine showed sustained (and increasing!) immune protection over time, perhaps from a robust early induction of memory immune cells (CD4 and CD8). The protection was strong and durable.”