SNY Sanofi

By Matthew Dalton and Joseph Walker 

PARIS -- A laboratory mistake has set back development of Sanofi SA and GlaxoSmithKline PLC's Covid-19 vaccine, delaying potential authorization by several months and complicating plans in the U.S. and Europe to quickly inoculate swaths of their populations next year.

Volunteers were accidentally given lower doses than intended in initial clinical trials due to a miscalculation in the manufacturing process, said Thomas Triomphe, Sanofi's executive vice president for vaccines.

Sanofi scientists, he said, will have to reformulate the vaccine to fix the problem with the goal of restarting clinical trials in February, and potentially securing regulatory authorizations in the fourth quarter of next year.

"It's a sad setback," Mr. Triomphe said in an interview. He estimated a delay of four months to five months. But "we prefer to take a step back, let the science work and come back with a product that is very efficacious in addition to being safe....You don't want to do compromises there."

U.S. and European public-health officials had high hopes that the vaccine could be developed in time to start distributing it to patients next year, a key part of their strategies to maximize vaccine supply.

Sanofi and Glaxo previously aimed for regulatory authorizations in the first half of 2021, but on Friday the companies pushed back that timeline to the fourth quarter.

The vaccine constitutes 10% of total global coronavirus vaccine doses that were expected from Western pharmaceutical companies next year, according to U.S. investment bank Jefferies Group.

European and U.S. health authorities have said they ordered more vaccines than their countries needed in the event some candidates failed.

Sanofi and GSK received $2.1 billion from Operation Warp Speed, the U.S. government's coronavirus vaccine program, to accelerate the development and distribution of the vaccine -- the biggest grant handed out by the U.S. program.

That deal called for the companies to supply the U.S. with 100 million doses and gave the government an option to order an additional 500 million. The European Union ordered 300 million doses, and the U.K. another 60 million.

Sanofi and Glaxo are two of the largest vaccine manufacturers in the world by revenue. Though usually fierce rivals, they teamed up this year in an unusual collaboration to jointly develop a vaccine, betting that by combining their scientific expertise and global operations reach they could move faster than by working alone.

Their vaccine combines a Sanofi-owned antigen -- a protein from the coronavirus that triggers immunity -- and a Glaxo-owned adjuvant, a molecule used in some vaccines to enhance the immune response

Friday's setback highlights the high-wire act of vaccine development in a pandemic, where even relatively mundane lab mishaps can have global consequences for public health.

"This shows what we know, that it is not always easy to develop a new vaccine to the point of being used to prevent the disease," said Stephen Evans, a professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine. "It is possible that adjustment of doses and constituents of the vaccine could improve responses in the elderly, but again, that is not guaranteed."

Mr. Triomphe said that the mistake occurred because of faulty lab materials, called reagents, that scientists were using to measure the potency of their antigen.

Sanofi used two different reagents made by separate manufacturers, but both wound up providing inaccurate measurements, Mr. Triomphe said.

"These reagents were not of high-enough quality or pure enough," said Mr. Triomphe. "The good news is that we can fix that."

Mr. Triomphe declined to name the manufacturers that produced the reagents.

The companies said that despite the dosing error, the vaccine showed encouraging results in volunteers age 18 years to 49 years. Yet it produced a weak immune response in people older than 50 years, a key demographic because they are more vulnerable to Covid-19.

Sanofi's reagent mishap is the second laboratory snafu in recent months to raise questions about the prospects of a leading vaccine candidate.

In November, AstraZeneca PLC and the University of Oxford said that a manufacturing error led to some patients receiving a lower-than-intended vaccine dose in clinical trials. In that case, the partners said the mistake may have been a happy accident because the lower dose showed greater effectiveness, though some experts have questioned whether the result will hold up after further testing.

One risk of the kind of vaccine technology used by Sanofi-GSK is that it was known going into the trial to produce weaker immune responses in older patients, said Penny Ward, visiting professor in Pharmaceutical Medicine at King's College London.

France was planning to begin its vaccination campaign this winter with the compound produced by Pfizer Inc. and BioNTech SE, the first coronavirus vaccine to be approved by regulators in the West, targeting nursing-home residents. France was planning to use the Sanofi-GSK vaccine as it starts inoculating the general public in the spring.

The Sanofi-Glaxo vaccine was expected to help ease the logistical challenges of mass vaccination since it can be stored at nonfreezing temperatures, unlike the Pfizer-BioNTech vaccine, which requires costly ultracold storage facilities.

Write to Matthew Dalton at Matthew.Dalton@wsj.com and Joseph Walker at joseph.walker@wsj.com

(END) Dow Jones Newswires

December 11, 2020 14:48 ET (19:48 GMT)

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