The Sanofi SA-Glaxosmithkline plc COVID-19 vaccine program is taking a step backward to recalibrate as weak interim phase I/II data showed an insufficient response in patients age 50 and older. The step is a large one, delaying a potential launch until mid-2021 at the earliest and the end of next year at the latest.
Those patients age 50 and older demonstrated a low immune response when treated with the vaccine, possibly due to an insufficient concentration of neutralizing antigen titers. Now the companies are prepping a phase IIb study for February to measure a reformulation. If that works, a phase III could begin sometime in the second quarter of 2021, followed by regulatory submissions in the second half of the year.
The vaccine, according to the two companies, showed a “transient but higher than expected levels of reactogenicity likely due to the suboptimal antigen formulation, with no serious adverse events related to the vaccine candidate.”
The best results came from the group that tested the highest antigen concentration, combined with the Glaxosmithkline adjuvant and showed neutralization titers in 88%. Seroconversion was found in 89.6% of the 18 to 49 age group. in 85% in the over-50 age group and 62.5% in those older than age 60.
Management from both companies took the big picture view and said they would continue pursuing the vaccine program. Thomas Triomphe, Sanofi Pasteur’s executive vice president, said the delay is disappointing “but all our decisions are and will always be driven by science and data.”
Those younger than age 50, however, did well in the phase I/II study as the interim data showed their immune response to the vaccine was comparable to those who have recovered from COVID-19.
The phase I/II, which began in September, is evaluating 441 healthy adults receiving one or two doses of the vaccine or a placebo 21 days apart at 10 sites across the U.S.
Sanofi and Glaxosmithkline were awarded about $2.1 billion in July from the U.S. Operation Warp Speed to support development and large-scale manufacturing of their adjuvanted recombinant protein subunit vaccine, providing the federal government with 100 million doses. The companies also have supply deals with the U.K., Canada and Gavi, an international vaccine alliance.
Meanwhile, the Russian Direct Investment Fund said Astrazeneca plc will incorporate one of two human adenoviral vectors from the Sputnik V vaccine in its COVID-19 clinical trials by the end of 2020.
Russia’s Sputnik V, a two-shot human adenovirus-based vaccine, hit 91.4% efficacy on day 28 after the first dose. The efficacy was greater than 95% 42 days after the initial dose based on data from volunteers who received both doses or placebo.
The vaccine, which was developed by the Gamaleya National Center of Epidemiology and Microbiology and funded by the Russian Direct Investment Fund, gained emergency use authorization in Russia on Aug. 11, and 1.2 billion doses-plus are on order from more than 50 countries. Sputnik V comes in a freeze-dried formulation and demonstrated 91.4% efficacy in a second interim analysis.
A phase III interim analysis of Astrazeneca-University of Oxford’s AZD-1222, a chimpanzee adenovirus vectored vaccine, demonstrated that the vaccine is safe and effective at preventing symptomatic COVID-19. The vaccine’s 70.4% efficacy is above the required 50% threshold but significantly below that of mRNA vaccines. For instance, efficacy jumped to 95% from the 90% found in an interim analysis of Biontech SE and Pfizer Inc.’s mRNA vaccine, BNT-162b2.
However, efficacy of AZD-1222 increased to 90% in a prime-boost arm of the trial in which volunteers received half a dose followed by a full dose.
AZD-1222 has a leg up on the Sanofi-GSK vaccine: It demonstrated the same immune response in healthy people aged 70 as was seen in those ages 18 to 55, and the older people had fewer side effects, in a phase II trial.
Astrazeneca’s management, SVB Leerink analyst Andrew Berens wrote on Dec. 11, said they are satisfied with AZD-1222’s efficacy and that the vaccine will be approvable in the EU and the U.K. They added, Berens said, that U.S. regulators will most likely require additional regional data from the ongoing U.S. trial as a base case.
Dr. Reddy’s Laboratories Ltd., of Hyderabad, India, and the Russian Direct Investment Fund are collaborating on an adaptive phase II/III study in India of Sputnik V, which comes in a freeze-dried formulation. The two are testing the vaccine’s safety and immunogenicity.