Sanofi and GSK Delay COVID-19 Vaccine Program Due to Insufficient Immune Response in Older Adults

Compiled by Keke

Just hours after the mRNA vaccine developed by Pfizer and BioNTech gained support from a U.S. FDA advisory panel, Sanofi and GlaxoSmithKline announced that their development program for an adjuvanted COVID-19 vaccine had suffered a major setback.

On December 11, Sanofi and GlaxoSmithKline (GSK) announced a delay in the trial plan for their adjuvanted recombinant protein-based COVID-19 vaccine to improve the immune response in the elderly population. According to the latest interim results from the Phase 1/2 study, the immune response in adults aged 18 to 49 who received the vaccine was comparable to that of patients recovering from COVID-19, but the immune response in the elderly population was lower. The two pharmaceutical companies believe this may be due to insufficient antigen concentration.

This Phase 1/2 clinical study was a randomized, double-blind, placebo-controlled trial designed to evaluate the safety, reactogenicity, and immunogenicity (immune response) of a COVID-19 vaccine candidate. A total of 441 healthy adults participated in the study across 10 research sites in the United States. Participants received one or two doses of the candidate vaccine or placebo at 21-day intervals.

Specific data showed that after two vaccine doses, the neutralizing antibody titers in participants were comparable to those in the serum of patients recovered from COVID-19. Cellular responses were balanced in adults aged 18 to 49 years, but neutralizing antibody titers were insufficient in adults aged 50 years and older. Participants exhibited transient but higher-than-expected reactogenicity levels, possibly due to suboptimal antigen formulation; no serious adverse events related to the vaccine candidate occurred. The most favorable outcomes were observed in the group receiving the highest antigen concentration combined with the GSK adjuvant, with 88% of participants showing neutralizing titers. Seroconversion rates were 89.6% in the 18–49-year age group, 85% in the ≥50-year age group, and 62.5% in the >60-year age group.

In addition, a recent challenging study conducted in non-human primates demonstrated that the vaccine developed by Sanofi and GSK could prevent pulmonary lesions and rapidly clear the virus from the nasal cavity and lungs within 2 to 4 days. The results of this preclinical study confirmed that the candidate vaccine has a strong capacity to inhibit viral replication through an optimal antigen formulation. These findings have bolstered both companies’ confidence in the ability of their adjuvanted recombinant platform to deliver highly effective vaccines for all adults.

GSK and Sanofi had projected the release of hundreds of millions of doses of their vaccines to the global market, accounting for a significant proportion of the vaccine doses required for the worldwide fight against influenza. The two companies signed an agreement with the World Health Organization (WHO) to collaborate on the equitable allocation of vaccines, ensuring supply to less affluent countries around the world.

Sanofi and GSK’s adjuvanted recombinant protein vaccine candidate was selected by the U.S. government’s “Operation Warp Speed” in July 2020 to accelerate its research, development, and manufacturing. The two pharmaceutical companies had originally planned to roll out their vaccine to countries by mid-2021, but due to these unfavorable results, the vaccine development program will be delayed.

Sanofi and GSK announced that Phase 2b clinical trials would commence in February 2021, supported by the Biomedical Advanced Research and Development Authority (BARDA) under the U.S. Department of Health and Human Services (HHS). This Phase 2b study will include a comparison with an already authorized COVID-19 vaccine. If the data are positive, global Phase 3 trials may begin in the second quarter of 2021. Positive results from the Phase 3 trials would support the two companies in submitting regulatory approval applications in the second half of 2021. However, even if everything proceeds smoothly, the vaccine is not expected to become available until the fourth quarter of 2021. The two pharmaceutical companies stated that they have notified governments with which they have supply agreements, including the U.S. government, under a $2.1 billion deal for 100 million doses of the vaccine.

References:

1.Sanofi-GSK COVID-19 Vaccine Hits Snag With Insufficient Immune Response in 50+ Population

2.Sanofi and GSK announce a delay in their adjuvanted recombinant protein-based COVID-19 vaccine program to improve immune response in the elderly

3.Sanofi, Glax­o­SmithK­line hit with a ma­jor de­lay on Covid-19 vac­cine pro­gram as their first jab flops in old­er adults