Two months after a clinical setback that delayed for at least a year the expected launch of their COVID-19 vaccine, Sanofi and GlaxoSmithKline (GSK) said today they have begun a new mid-stage study of a “refined” formulation of their adjuvanted recombinant protein-based candidate, with plans to advance to Phase III next quarter and reach the market by year’s end.
Sanofi and GSK said they have begun testing their COVID-19 vaccine candidate in a Phase II trial (VAT00002; NCT04762680) that is expected to recruit 720 volunteer participants ages 18 and older, with the goal of selecting the most appropriate antigen dosage for a Phase III study expected to begin in the second quarter. Should the results of that study prove positive, the companies said, they will pursue approvals designed to bring the vaccine to patients during the fourth quarter.
“Over the past few weeks, our teams have worked to refine the antigen formulation of our recombinant-protein vaccine, based on learnings from our initial Phase I/II study,” Thomas Triomphe, executive vice president and Head of Sanofi’s vaccines unit Sanofi Pasteur, said in a statement.
That study (NCT04537208) produced interim results showing that the vaccine generated insufficient neutralizing antibody titers in adults over the age of 50, “likely due to an insufficient concentration of the antigen,” GSK and Sanofi said on December 11 in announcing the clinical setback, and restated today.
The statement suggests that the companies may have reformulated their vaccine by increasing the concentration of antigen. However, Sanofi and GSK offered no details in their announcement about how they refined the antigen formulation of their vaccine candidate—except to say it was designed “to achieve optimal immune response, including in older adults.”
Sanofi antigen, GSK adjuvant
The companies’ COVID-19 vaccine candidate incorporates Sanofi’s S-protein COVID-19 antigen, which is based on recombinant DNA technology; and GSK’s pandemic AS03 adjuvant. “We are confident that our vaccine candidate has strong potential and we are very encouraged by the latest preclinical data,” Triomphe said. The companies’ statement did not summarize, let alone detail, that preclinical data.
To assess that potential, Sanofi and GSK have begun their new Phase II trial, a randomized, double-blind, multi-center dose finding study conducted in adults aged 18 years of age and older that is designed to evaluate the safety, reactogenicity, and immunogenicity of two injections given 21 days apart. The trial will include equal numbers of adults 18 to 59 years and those 60 years and above.
GSK and Sanofi plan to test three different antigen doses with a fixed dose of adjuvant in their total study population of 720 volunteers in the U.S., Honduras, and Panama. Results of the Phase II trial will inform the protocol of the Phase III trial, set to start in the second quarter. Positive results from the Phase III trial would be followed by submissions to regulators in the second half of this year, with the vaccine expected to be available in Q4 2021.
The new trial is being funded through the U.S. government program launched last year by the Trump administration to accelerate development of COVID-19 vaccines and drugs. The program, whose original name “Operation Warp Speed” was dropped by the Biden administration, awarded the companies up to $2.07 billion in funding in July 2020.
“The world needs multiple vaccines and we are confident that combining our proven pandemic adjuvant system with this improved antigen formulation will have significant potential as the pandemic evolves,” added Roger Connor, president of GSK Vaccines.