FDA slams the door in Humanigen's face, rejects emergency use green light, wants more data

After riding high in 2021 on some broadly positive COVID data and high hopes for a speedy authorization, Humanigen has come crashing back down to earth.

Early Thursday morning, Humanigen said the FDA has rejected giving the biotech an emergency use authorization (EUA) for its COVID drug hopeful lenzilumab in patients hit with the disease and in hospital. The Californian company had asked the FDA to hand out the EUA for its drug, which it believed could help calm the so-called “cytokine storm” that can hit some COVID patients.

The FDA, however, wants more data, telling Humanigen that “it was unable to conclude that the known and potential benefits of lenzilumab outweigh the known and potential risks of its use as a treatment for COVID-19.”

In a statement, Humanigen said the FDA “has invited Humanigen to submit additional data as it becomes available,” which the biotech thinks could come from the NIH’s so-called ACTIV-5/BET-B study, which “is expected to provide further data that may support a new EUA request.” The company did not give a timeline for the trial, or when the EUA may be re-submitted.

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Humanigen had also been talking up a potential full approval via a BLA, but that will likely now be off the table for the immediate future.

In a recent trial, investigators randomized 520 hospitalized COVID-19 patients to receive an infusion of lenzilumab or placebo on top of standard-of-care treatments such as dexamethasone and Gilead Sciences' Veklury.

In the data posted in March, after 28 days, the rate of ventilator-free survival was higher in the lenzilumab arm, causing the trial to hit its primary endpoint with a p-value of 0.0365. Humanigen changed the primary endpoint twice in the months after initiating the phase 3 trial in April 2020. 

In the treatment group, the Kaplan-Meier estimate for invasive mechanical ventilation and/or death was 15.6%, compared to 22.1% in the placebo group. Humanigen also reported a “favorable trend” in the mortality rate, which was 9.6% in the lenzilumab arm and 13.9% in the placebo group.

“We remain committed to bringing lenzilumab to patients hospitalized with COVID-19,” said Cameron Durrant, M.D., CEO at Humanigen.

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“We believe the ongoing ACTIV-5/BET-B trial, which has been advanced to enroll up to 500 patients, may provide additional safety and efficacy data sufficient to support our efforts to obtain an EUA to treat hospitalized COVID-19 patients.”

Humanigen, formerly KaloBios and once run by the imprisoned “Pharma Bro” Martin Shkreli, has also sent off for a review for the med to be used in the U.K., with a decision yet to be reached.

Lenzilumab targets GM-CSF, a cytokine associated with negative outcomes in COVID-19 patients. By neutralizing the cytokine, drug developers including Humanigen and GlaxoSmithKline have predicted that they may be able to counter life-threatening complications that arise when the immune system reacts particularly strongly to the virus.

Recent top-line data from a phase 3 had shown lenzilumab in hospitalized COVID-19 patients met its primary endpoint, sending Humanigen's shares rocketing, with expectations even higher. Analysts at Jefferies had previously guided that Humanigen would likely win an EUA, while those at Cantor had predicted blockbuster sales of $1 billion, but that now remains in serious doubt.

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Hospitalized patients have proven difficult to treat with other COVID-19 drugs. Anti-SARS-CoV-2 antibodies have struggled in the population, potentially because in hospitalized COVID-19 patients the immune response is as much of a factor as the virus itself. Researchers have tested other drugs designed to tamp down immune responses, including Roche’s Actemra and Sanofi’s Kevzara, with mixed results.  

Humanigen's shares were more than halved in early, pre-market trading Thursday on the news, down 52% to just over $7 a share.