Setback for Sanofi/GSK COVID-19 vaccine highlights importance of portfolio strategy
A delay in the development of Sanofi and GSK’s COVID-19 vaccine due to a lack of efficacy in older adults reinforces the importance of the portfolio strategy governments are taking in procuring a COVID-19 vaccine.
Partners Sanofi (Euronext:SAN; NASDAQ:SNY) and GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) announced Friday that regulatory submissions for its COVID-19 vaccine would be delayed by about six months after Phase I/II data showed the vaccine did not provide adequate neutralizing antibody titers in adults >60 years old.
The U.S., U.K. and EU have spread their vaccine bets out across several different candidates and modalities to protect against such setbacks. The U.S. and U.K. have deals for seven different vaccine candidates, while the EU has deals in place for six.
With a procurement deal for 300 million doses of the Sanofi/GSK vaccine, the EU will be the hardest hit by the partners’ delayed timeline. Meanwhile, the U.K. has agreed to procure 60 million doses, while the U.S.’ Operation Warp Speed has allocated $2 billion to support the vaccine, including procurement of 100 million doses.
The partners had originally hoped to launch a global, placebo-controlled Phase III trial this month with data and regulatory submissions coming in 2Q21.
Instead, Sanofi and GSK now plan to start a Phase IIb trial in February that will test an “improved antigen formulation” that the companies hope will illicit a higher immune response across all age groups.
However, given the likelihood that at least two and up to four other COVID-19 vaccines could be authorized by then, the Phase IIb trial and subsequent Phase III trial slated to start in 2Q21 may have an authorized COVID-19 vaccine rather than placebo as the control arm.
On Thursday, FDA’s Vaccines and Related Biologic Products Advisory Committee (VRBPAC) voted 17-4 in favor of recommending emergency use authorization (EUA) for mRNA COVID-19 vaccine BNT162b2 from Pfizer Inc. (NYSE:PFE) and BioNTech SE (NASDAQ:BNTX), with an EUA expected as early as today. The VRBPAC is reviewing an EUA submission for mRNA-1273 from Moderna Inc. (NASDAQ:MRNA) on Dec. 17.
Both mRNA vaccines have been the standout performers, demonstrating about 95% efficacy in Phase III trials. Such high efficacy would set a high bar for any non-inferiority trial designs that include either one as an active comparator.
AstraZeneca plc (LSE:AZN; NASDAQ:AZN) and partner the University of Oxford reported Phase III data for adenovirus-based AZD1222 that exceeded FDA’s efficacy requirements, but questions about the levels of protection it could provide remain given that a half-dose/full-dose regimen showed 90% efficacy in one trial, while a second trial of two full doses showed only 62% efficacy.
Despite the questions, AZD1222 is already under review in Europe and the U.K. and very likely could be available before February.
And another adenovirus-based vaccine, JNJ-78436735 from Johnson & Johnson, could have Phase III data for a single-dose regimen by year-end or early January, with a potential EUA coming as early as February.
The Sanofi/GSK vaccine is a protein-based vaccine that uses GSK’s pandemic adjuvant. In the Phase I/II trial in 441 healthy adults, seroconversion was 89.6% in adults 18-49 years old and 85% in the >50 years old group, but only 62.5% in the >60 years old group. Most other vaccines that have reported data have shown 100% or near 100% seroconversion rates.
The partners did note that a recent challenge study in non-human primates using an improved antigen formulation showed protection against lung pathology and rapid viral clearance in two to four days.
Further details from the Phase I/II trial will be published in a peer-reviewed publication in the coming days, the companies said.