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One of the world’s leading vaccine manufacturers has suffered a major setback in its work to produce a Covid-19 vaccine. The problem will push the timeline for deployment of Sanofi Pasteur’s vaccine — if it is approved — from the first half of 2021 into the second half of the year, the company said Friday.

The news is not just disappointing for Sanofi and its development partner, GlaxoSmithKline, which is providing an adjuvant used in the vaccine. The companies have contracts with multiple countries, including the United States and Britain, as well as the European Union.

Sanofi had hoped to start a Phase 3 trial of the vaccine this month and had projected it could produce 100 million doses of vaccine in 2020, and 1 billion doses in 2021.

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The problem relates to inadequate results in older adults in Sanofi’s Phase 1/2 trial, which the company traced back to an inadequate formulation of their vaccine, Su-Peing Ng, global medical head for Sanofi Vaccines, told STAT in an interview.

Ng said both Sanofi and GSK are committed to continuing work on the vaccine, and plan to begin a Phase 2b trial in February.

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“We’re disappointed that there is a delay,” she said. “I think, though, that we’re encouraged that we have enough information, enough of the results from preclinical and clinical [studies] to tell us that we have a path forward. We need to optimize this formulation.”

In effect, participants in the trial received too little vaccine. While the too-small dose generated adequate levels of neutralizing antibodies in adults aged 18 to 49 in the trial, adults 60 and older generated lower levels of neutralizing antibodies than are seen in the blood of people who have recovered from Covid-19 infection, Ng said.

Perplexed by the findings, the company set out to figure out why the vaccine underperformed. It discovered two commercial reagents used to measure how much antigen — active vaccine — was included in each dose were giving false readings. In fact, Ng said, the concentration of the antigen “was insufficient.”

A revised formulation, tested recently in non-human primates, showed the vaccine prevented damage in the lungs, which is what triggers severe Covid disease in people, and led to rapid clearance of the virus.

The vaccine’s path will be more challenging because of this delay; the Covid vaccine landscape is changing daily and placebo-controlled trials may not be feasible for much longer, with the first vaccines soon to be deployed. If people know they may soon have access to an authorized vaccine, there is less motivation to enroll in a trial where they might get a placebo.

Sanofi knows this and is proposing to the Food and Drug Administration that its Phase 2b trial compare its vaccine to one that is already authorized, not a placebo.

“To continue to provide confidence that we’re going to have a vaccine that meets the expected standard of care, we propose the comparison with an authorized Covid-19 vaccine instead of placebo control,” Ng said.

That would set a very high bar for the Sanofi vaccine. Pfizer and Moderna, the front-runners in the vaccine race, have reported vaccine efficacy of about 95% in their Phase 3 trials. If the Sanofi vaccine doesn’t reach that level of efficacy, can it be brought to market, STAT asked Ng.

“That will be up to the regulators,” she said, adding that “for the public to be confident in the choice of a vaccine, it would have to be pretty close to what’s been established now.”

The Sanofi vaccine would have one advantage compared to the Pfizer and Moderna vaccines: It wouldn’t require ultracold storage and could instead be kept in standard refrigerators, making it easier to distribute.

Pfizer and Moderna are poised to receive emergency use authorizations from the FDA this month — an FDA advisory panel endorsed the Pfizer shot on Thursday — and vaccine rollout in the United States is expected to begin within days of the FDA’s green light. The Phase 3 trial for Johnson & Johnson’s vaccine — the only one-dose vaccine currently in clinical trials in the U.S. — is about to finish enrollment; if it is effective, it could get an EUA in the first quarter of 2021.

The Sanofi vaccine is made with an approach the company uses for one of its flu vaccines, Flublok. That in theory is an advantage; the FDA knows how this vaccine system works. It’s called a recombinant protein vaccine, with the spike protein of the SARS-CoV-2 virus, which cases Covid-19, generated in insect cells.

Sanofi is also developing a second vaccine, a messenger RNA vaccine, like the Pfizer and Moderna shots. For this project, it is collaborating with Translate Bio, a Lexington, Mass.-based biotech. Clinical trials for that vaccine have not yet begun.

  • Of the placebo recipients in your (and other company’s) trials, how many of those in the placebo groups ultimately developed covid or were asymptomatic?
    Thanks!
    Respectfully,
    Caryn Westmeier

  • The key takeaway from this article is how the FDA needs to be completely reformed. The standard that what reaches the market has to be better than what is already on the market in trials is so ignorant, it defies belief.

    First, unless there is supply for 100% of the population, they need any vaccine they can find. As long as it’s efficacy is 60% or higher, release it

    Second, trials are a very small snapshot of the treatment. Maybe this one is safer, works on certain populations better, or holds immunity longer. The FDA sniffing this out before release prevents that answer.

    The FDA is flawed to the core, these two examples are the just the tip of the iceberg.

    • Erik, the FDA does not require that a new product must be more effective than an adequately effective product already on the market. The new product may be less effective than a previously licensed one as long as it is deemed to be effective enough. As you rightly point out, a slightly less but adequately effective product might have other advantages, and in case of a product shortage could be a useful alternative to fill the void.

    • Amelia, did you read the article? Their vaccine director is clearly concerned their vaccine may get rejected due to differences in efficacy.

      I realize the FDA does approve treatments that are less effective, but that should not even be a consideration.

    • I did read the article. I spent almost 30 years at the FDA as a vaccine reviewer, then supervisor of vaccine reviewers. I hope my comments are clarifying and reassuring.

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  • I am going to agree with another person who commented that Sanofi-Pasteur and GSK need to “stop trying to reinvent the wheel”, and work with other labs and companies that are developing similar vaccines – although sooner than the Sanofi-Pasteur’s timetable(end of 2021). They have the global manufacturing capacity and resources other smaller organizations don’t have.

    Novavax in the US and across the globe “Vector” Research Center(in Russia) are likely to have a recombinant viral protein particle vaccine(NVX-CoV2373 and EpiVacCorona) ready in the 1st months of 2021. Sooner than Sanofi/GSK. But both have limited manufacturing capacity of their own – a problem not faced by the latter 2 companies.

    If the current stage III and IIB trials in the UK and South Africa of the Novavax vaccine show success of at least 70%(random hypothetical percentage) it may be prudent for Sanofi-Pasteur to throw its resources behind Novavax in the US and help build up a vaccine supply in North America(where Pfizer is forecast to come up short in supply in the early crucial months of 2021) as soon as possible. Likewise Sanofi-Pasteur also has a presence in Russia as a vaccine supplier and a joint manufacturing agreement with “Vector” would also benefit them there as well. Otherwise they will end up being labeled the “pros” who came last behind the “rookies”.

    I personally would prefer taking the Novavax vaccine(or something similar) which will not be based on new mRNA technology, the long term effects of which are still to be determined in the future. Viral spike protein particles may not sound as “cool” as genetic engineering, but should be more acceptable to a nervous and distressed public.

    • It worked for a well defined, large part of the population. Why not move forward? Save other vaccines for those too old for this one. Something is missing here. Was this some twisted idea of fairness, or is there more to this story?

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