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2nd time lucky for Sanofi-GSK after passing small midstage COVID shot; eye approval by year-end

Read more at www.fiercebiotech.com

After fumbling their first attempt, once rivals but now partners Sanofi and GlaxoSmithKline have passed a small phase 2 COVID-19 vaccine test, plotting a much larger phase 3 in the coming weeks and a late 2021 approval.

The data are very top-line, with results yet to be published in a journal (though we’ve become used to that over the past year), but the headlines look encouraging for the vax: Its adjuvanted recombinant shot “achieved strong rates of neutralizing antibody responses,” which the pair said was “in line” with those measured in people who have recovered from COVID-19.

The test, in adults aged 18 to 95 years, was only in 722 volunteers in the U.S. and Honduras, but the inoculation after both shots (and across all doses) showed 95% to 100% seroconversion (when your immune system responds by producing antibodies in response to the virus).

Sanofi told Fierce Biotech the trial recruited participants “with racial diversity” including 64% white, 9% American/Alaskan Native, 8% African American and 5% Asian (with around 11% unknown). It added that 28% were of Hispanic ethnicity.

Overall, its candidate “elicited strong neutralizing antibody levels that were comparable to those generated by natural infection, with higher levels observed in younger adults (18 to 59 years old),” the pair said. 

After a single injection, high neutralizing antibody levels were seen in participants with evidence of prior SARS-CoV-2 infection; Sanofi and GSK said this suggests “strong potential for development as a booster vaccine,” which may be, in countries already using or buying up other vaccines, its main market in the future.

RELATED: After setback, Sanofi, GSK take tweaked COVID-19 vaccine into phase 2

It safety was clean, but, in such a small study, that means little; with clotting concerns from fellow Big Pharmas AstraZeneca and Johnson & Johnson, this will likely be of major importance to regulators. We still don’t know whether it can help stop infections nor reduce death or hospitalizations as the test was geared up only for immune responses, following the same path as COVID vaccine developers before it.

That will all need to be shown in its pivotal phase 3 study, which should be made up of 35,000 subjects and is expected to start “in the coming weeks.” This will work as a randomized, double-blind, placebo-controlled study with the middle 10-µg dose in combination with GSK’s pandemic adjuvant.

This tougher study than what we’ve seen before is what “regulators are asking for registration,” Sanofi said, as it looks toward a full approval and not just an emergency use authorization. It will also be geared toward the new variants emerging across the world.

Sanofi told Fierce Biotech that although the phase 2 was intentionally limited, it has given the partners “the confidence” to move on to the late-stage study. Commercial production will start as soon as the phase 3 starts, a risky bet for the company, given that if all falls through, they would have produced many doses for nothing. It did not give specifics of how many it will be making this year. 

The trial will be undertaken across “a broad range of countries” and will assess the efficacy of two vaccine formulations including the D614 (Wuhan) and B.1.351 (South African) variants.

It’s still getting the final signoff for the phase 3 and is staying mum on exactly which countries it had chosen for the tests, but in a call with journalists early Monday morning, led by Thomas Triomphe, executive vice president and and global head of Sanofi Pasteur, the company admitted to the “operational difficulties” of the trial, which will need to compete against high rates of vaccination in the U.S., U.K. and Israel as well as increased dosing across Europe, Russia, China and other countries.

It may well be that many in these regions have already had a shot, or are expecting one, and be unwilling to trial an experimental inoculation—a reversal of the situation last year, where people were signing up to COVID trials in droves. Sanofi did, however, point out that many parts of the globe are still in need of a vaccine and will want to be a part of its phase 3, including countries in Asia and Latin America, where the virus is also still circulating at a high enough rate for the trial.

In parallel, the companies will also work on booster studies with various variant formulations in order to assess the ability of a lower dose of the vaccine to generate a strong booster response, regardless of what shot they have had. These will not need efficacy results, Sanofi said on the call, but rather immunogenicity data, and tests can be done in countries like the U.S. or U.K. where the virus is on the downward path alongside major vaccine uptake.

The booster market appears to be, in the West at least, its main future market opportunity if it can be used after initial doses of other vaccines.

This all comes after the pair was hit by a setback for the vaccine: In last year’s phase 1/2 clinical trial, the original formulation of the Sanofi-GSK vaccine failed to trigger the desired immune response in adults aged 50 years and older.

The holdup, which followed stellar phase 3 data on rival vaccines, prompted Sanofi and GSK to go back to the laboratory in an effort to come up with a more effective candidate. A tweak of the vaccine was made, and, in February, it kicked off the phase 2, which seems to have borne out its change.

If all goes well in the late-stage trials and it gets the nod from regulators, the vaccine “is expected to be approved in the fourth quarter of 2021.”

Sanofi and GSK’s adjuvanted protein-based technology could be better suited to protecting people against multiple circulating variants than other platforms.

The virus-based approaches used by AstraZeneca and J&J may confer vector immunity that limits the effectiveness of repeat dosing. Equally, Moderna and Pfizer-BioNTech may struggle to provide protection against multiple variants in a single vaccine without causing levels of immune stimulation that make tolerability an issue.

Sanofi and GSK, in contrast, can potentially keep levels of immune stimulation constant—by using the same dose of adjuvant—while including additional antigens to protect against multiple variants in a single vaccine. Novavax’s COVID-19 vaccine is based on similar technology.

Sanofi is also working on an mRNA approach with biotech Translate Bio, but this is further back in testing; it’s also lending a hand with manufacturing other vaccines. 

Read more at www.fiercebiotech.com

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