Sweeping doubts aside, Eli Lilly beats Regeneron to emergency OK — clearing low dose antibody for quick rollout

Eli Lilly has clinched the first emergency use authorization issued for an antibody against Covid-19, setting in motion a $1.2 billion deal to supply the feds with the drug — albeit at a dose that failed the primary endpoint in a key trial.

Prioritizing a reduction in Covid-19-related hospitalizations or visits to the ER, the FDA opened the door for physicians to give 700 mg/20 mL injections of the drug, dubbed bamlanivimab, to recenly diagnosed, non-hospitalized patients who don’t need extra oxygen due to the coronavirus infection.

The emergency OK puts Lilly ahead of close rivals at Regeneron, which announced the EUA filing for its antibody cocktail on the same day despite starting clinical trials slightly later. That was also the day — October 7 — President Donald Trump declared without evidence he’s already authorized the Regeneron drug, which he received as part of his Covid-19 treatment.

In the EUA letter, FDA chief scientist Denise Hinton wrote the agency based its decision on topline data from the interim analysis of BLAZE-1 and concluded it is “reasonable to believe that bamlanivimab may be effective for the treatment of mild to moderate Covid-19” for patients who are 12 or older, weigh at least 40 kg, and are at high risk of progressing.

As is customary, she didn’t break down the exact numbers regulators reviewed. But analysts have been puzzled by the lack of dose-dependent response in the Phase II trial: Out of three doses tested, only the middle, 2800 mg dose hit the primary endpoint of reducing viral load at statistical significance. The results that Lilly recently published in the New England Journal of Medicine raised further questions about just how effective the low dose of bamlanivimab is.

The 700 mg dose, meanwhile, cut viral levels by only 0.20 compared to placebo, for a p-value of 0.38, far below the 0.05 threshold long considered the industry standard.

Lilly’s argument for asking the FDA to authorize — and convincing the feds to purchase — the low dose was that “similar clinical effects were seen across all dose levels,” which was the metric that mattered. In a new statement, CSO Daniel Skovronsky highlighted that it appeared to reduce Covid-related hospitalizations.

The FDA apparently agreed with the company, noting in a press release:

However, the most important evidence that bamlanivimab may be effective came from the predefined secondary endpoint of COVID-19-related hospitalizations or emergency room visits within 28 days after treatment. For patients at high risk for disease progression, hospitalizations and emergency room visits occurred in 3% of bamlanivimab-treated patients on average compared to 10% in placebo-treated patients. The effects on viral load and on reduction in hospitalizations and ER visits, and on safety, were similar in patients receiving any of the three bamlanivimab doses.

Going with the lower dose also meant that the same amount of drug material could serve four times as many patients as a 2800 mg regimen could, a crucial difference given limited manufacturing capacity.

The antibody formerly known as LY-CoV555 now joins convalescent plasma on the roster of treatments with an EUA, with remdesivir recently graduating to full approval status as Veklury.

HHS has agreed to pay $375 million for 300,000 vials of that dose, which it said is good for a 2-month supply. The government has an option on another 650,000 doses on the same terms, meaning $812 million more in potential revenue for Lilly and AbCellera, which originally developed the drug in collaboration with the NIH.

The next step will be getting the manufacturing in order after inspectors found quality control problems at a New Jersey plant Lilly is using to meet its goal of producing 1 million doses of the antibody by year end.

Most of that will likely go to outpatients after the NIAID shuttered a study testing bamlanivimab in combination with remdesivir for those hospitalized with Covid-19 , after losing faith it could help sicker patients.

Lilly is also developing a cocktail that combines bamlanivimab with etesevimab from Junshi Biosciences, with a snapshot of results that had impressed commentators.

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