GSK and Vir, navigating early antibody pitfalls, tout delta variant-busting data for latecomer sotrovimab

While several vaccines now stand tall in the fight against COVID-19, therapies—and antibody drugs in particular—have had a decidedly tougher time. Saddled with access issues and beset by fast-emerging variants, firstcomer Eli Lilly has recently been forced to rethink its tactics. Now, GlaxoSmithKline and Vir Biotechnology are applying those lessons to their solo agent sotrovimab.

Backed by promising phase 3 data and lab results showing efficacy against a suite of virus variants including the lurking delta variant, sotrovimab still has a big role to play in the pandemic, executives from GSK and Vir said in a recent joint interview with Fierce Pharma and Fierce Biotech.

Federal officials seem to agree. Late last week, the U.S. paused the distribution of Eli Lilly’s combo of bamlanivimab and etesevimab until further notice, citing the ascent of the gamma and beta variants stateside. With Lilly’s drug struggling to keep pace with mutations, the Assistant Secretary for Preparedness Response and the FDA urged healthcare providers to switch to other authorized antibodies like sotrovimab and Regeneron’s cocktail REGEN-COV, both of which are “likely to retain activity” against the gamma and beta variants, which now make up more than 11% of sequenced U.S. coronavirus cases, ASPR said in a release.

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But sotrovimab—priced at $2,100 in the U.S.—isn’t stopping there, George Scangos, Ph.D., president, chief executive officer and director at Vir Biotechnology, said.

The sotrovimab approach

To develop its drug, Vir “deliberately isolated an antibody that binds to a part of the virus that is very difficult for the virus to mutate,” he said. That piece of the virus is “conserved, not only in all the variants, but in SARS-1 … and in a whole family of coronaviruses.”

Vir knew the variant onslaught was coming, said the company's executive vice president of research and chief scientific officer, Herbert “Skip” Virgin, M.D., Ph.D. So far, added Scangos, its premise of targeting a conserved site to maintain efficacy against mutations “seems to be holding true.”

Sotrovimab “appears to retain activity against variants of concern” like alpha, beta, gamma, epsilon and iota, the National Institutes of Health noted in recently updated COVID-19 treatment guidelines. Last week, GSK and Vir provided data suggesting that delta also belongs to that list. Updated lab experiment data posted on the preprint repository bioRxiv showed sotrovimab’s activity against 14 variants including the troubling delta variant—which first surfaced in India and appears to spread more rapidly than the already-speedy alpha—was very similar to that against the original SARS-CoV-2 virus.

Vir studied its drug’s efficacy using the common IC50 marker, which essentially measures the concentration needed for an intervention to inhibit 50% of infection in cells.

The site the partners’ antibody binds to isn’t just conserved from SARS-CoV-1 and SARS-CoV-2 but also across “many sarbecoviruses”—the viral grouping to which both coronaviruses belong, he said. Vir was already aware that SARS-1 varies to get away from antibodies, “so there was no reason to expect that SARS-2 would not.”

Meanwhile, it wasn’t just about what Vir would target, but what it wouldn’t, Virgin pointed out. The company “wanted to avoid” the “hyper-variable parts of the viral spike,” where many mutations have occurred.

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Sotrovimab is flying high on its own, and leveraging the drug as a solo agent will remain Vir and GSK’s plan for the foreseeable future, Scangos said.

“That being said, we are conscious of the fact that although we cover all existing variants that are around today," the company can’t count on that always being true, he noted.

The company is advancing its own second-generation antibodies that pair well with sotrovimab and plan to bring forward a combination of sotrovimab with a second antibody, he said.

Adding a similarly effective antibody to sotrovimab, which already seems to work against the current mutations, has the potential to be “truly variant-proof” or “as close to variant proof as you could do,” Scangos added.

The commercial piece

Meanwhile, questions remain about how GSK and Vir will sell their product. Sotrovimab won its FDA emergency nod in late May but didn’t receive a supply deal with the U.S. government like the drugs from its mAb predecessors, Lilly and Regeneron.

With the companies planning to file for a full approval in the second half of the year, GSK and Vir will be turning to its already established “existing commercial channels” in the U.S., Victoria Williams, vice president and medicines commercialization leader for sotrovimab at GSK, said. At a wholesale acquisition cost of $2,100 in the U.S., the drug is in the reported price range of other antibodies, she said.

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While the companies are in an admittedly different “commercial setting” than Lilly and Regeneron, “we felt that it was important to be in that same [price] range,Williams said. Government supply deals will certainly “remain a route in a number of different countries,” she added.

Earlier-to-market antibodies from Lilly and Regeneron have struggled with uptake, thanks to tight treatment windows, inconvenient infusions and, most recently, variant susceptibility. GSK and Vir are now looking to counter some of those pitfalls with sotrovimab, Williams said.

She highlighted three key pain points in the patient journey: access, the tight timeframe within which antibody treatment is optimal and having the capacity to infuse patients.

“I think many healthcare systems have got the capacity piece organized,” Williams noted. “Where the issues have been” include awareness about the tight treatment window and how to find patients in time and give them access to receive the mAb.

Working that angle, GSK is teaming with governments on measures like scaled healthcare professional education programs. It is also collaborating with countries’ health systems to create automatic alerts when a high-risk patient tests positive for COVID-19. In addition, GSK is looking at ways to support infusion centers in Canada, but by and large, it’s having to strategize country-by-country, Williams explained.

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As far as supply is concerned, the companies currently have about 450,000 sotrovimab doses on hand, Vir’s Scangos said. The companies are also revving up their manufacturing network to crank out roughly 2 million doses for the first year of emergency supply in the U.S. The antibody itself is made by WuXi and Samsung Biologics in China and South Korea, respectively, before it’s finished and distributed from GSK’s facility in Parma, Italy, Scangos said.

Samsung is currently coming online with high-volume manufacturing, and the companies “think in the following year, we can make many more than two million doses available,” he added.

The partners are also working on a formulation that can be delivered as an intramuscular injection, which many patients and healthcare providers prefer over infusions, Williams noted.

"Vaccinal" antibody allure

So far, antibody drugs have exclusively been authorized to treat mild-to-moderate COVID-19, with use limited to patients who aren’t hospitalized but are at high risk of progressing to severe disease. That treatment window has proven tricky for Lilly and Regeneron, but Vir and GSK “have a second approach,” Virgin said.

While sotrovimab is basically a half-life extended version of a natural human antibody, the company has another prospect in the hopper, VIR-7832, which is built to be better than natural antibodies and could be relevant to more severe COVID-19 cases, he said. Specifically, the antibody is enhanced to trigger T cells alongside the benefits of sotrovimab. The hope is that the drug would not only offer therapeutic benefits but also confer a vaccine-like effect, potentially making it a meaningful weapon for prevention.