Humanigen Announces Positive Trial Data for COVID-19 Antibody, Drawing Criticism

Humanigen on Friday revealed positive interim data in a late-stage clinical trial of its monoclonal antibody lenzilumab for the treatment of COVID-19 patients, but a trial design expert contended that the disclosure was inappropriate and could put the trial’s integrity at risk.

The company announced that an interim analysis from the trial — which uses an adaptive design in which the information gathered during the trial can lead to changes — suggested the antibody had a clinically meaningful effect on patient recovery. The company says the data predicts approximately 37 percent more recoveries in patients who received lenzilumab compared to the group receiving standard of care.

But the release of the information isn’t typical, could cause bias within the trial and will likely draw scrutiny from the FDA, said Scott Berry, president and senior statistical scientist at adaptive trial design firm Berry Consultants. The company disputes that characterization.

Berry said: “What is a concern within a trial is if information gets out that changes inherently the trial, the patients that are enrolled [and] the behavior of patients in the trial in a way that risks the credibility of the scientific information; that’s referred to generally as ‘operational bias’,” Berry told FDAnews. “What’s very clear is they have not reached statistical significance, they have not demonstrated that the drug is effective, but yet they have sent out information that very much alludes to that fact.”

Berry explained that the FDA has published guidance on adaptive trials that stresses the importance of protecting information in a trial and keeping it from reaching the public to avoid operational bias. Specifically, the agency strongly recommends “that access to comparative interim results be limited to individuals with relevant expertise who are independent of the personnel involved in conducting or managing the trial.”

Humanigen’s announcement goes against that guidance, Berry said, and while it’s unlikely the FDA will ask the company to stop the trial, they will likely ask them to show their actions didn’t have an effect on it.

“I don’t think this is a deathblow to their trial, [but] … they’re going to be asked to analyze the data before and after the announcement,” he said. “They’ve brought undue scrutiny to the analysis at the end because of their actions, but it doesn’t mean it’s a deathblow.”

A Humanigen spokesperson told FDAnews that the company stands by their decision to release the data, calling the disclosure of analyses of unblinded interim data “common practice.”

“We are encouraged by these data, in which investigators, patients, contract research organizations and company representatives remain blinded to” the data, the Humanigen spokesperson said. “We are operating in a pandemic environment where access to information is vital to improve patient outcomes while maintaining study integrity.”

Humanigen also announced Friday that it has been granted a Biomedical Advanced Research and Development contract that will see the company receive Operation Warp Speed (OWS) support for lenzilumab. The contract does not include a funding component at this point, the company explained, as its focus is on generating a more efficient Emergency Use Authorization (EUA) and potential Biologics License Application (BLA) submission by giving Humanigen access to regulatory, manufacturing and statistics experts.

Humanigen was briefly run by “pharma bro” Martin Shkreli in 2015, when it went by the name KaloBios Pharmaceuticals. — James Miessler