Is that all? FDA committee reviewing Incyte's anal cancer drug flags bevy of trial concerns from deaths to diversity

A study for Incyte's anal cancer drug had a tiny study population. Ten patients appear to have died due to treatment-related adverse events. Barely any non-white patients participated and well, it wasn't even all that effective. 

And that's not all, according to an FDA advisory committee reviewing the therapy for an early approval.

The FDA's Oncologic Drugs Advisory Committee (ODAC) voted 13-4 Thursday to defer a regulatory decision on Incyte's PD-1 inhibitor retifanlimab.

Of the first 76 approvals for immune checkpoint inhibitors, 35 were given the accelerated pathway, according to the committee. Incyte was hoping to land in that exclusive—and often lucrative—club, but the vote provides the agency with some food for thought as it mulls the decision. 

Advisory panels like ODAC provide advice, but the FDA does not have to follow it. The agency typically falls in line with the recommendations, but sometimes goes another way entirely, which was the case with Biogen's Alzheimer's disease drug Aduhelm earlier this month. 

In the case of retifanlimab, ODAC determined that data from a phase 2 trial, dubbed POD1UM-202, was not sufficient. The committee would prefer to see data from a confirmatory trial that's currently underway to assuage concerns.

Data from that trial is not expected to be ready until the fourth quarter of 2024, according to analysts from Mizuho.

The news is a blow as Incyte hopes to become the first FDA-approved treatment for patients with anal cancer who have progressed after first-line chemotherapy. Retifanlimab is aimed at patients with metastatic squamous carcinoma of the anal canal who have progressed on or are intolerant of platinum-based chemotherapy. Incyte paid MacroGenics $150 million upfront in 2017 for the global rights to retifanlimab.

RELATED: Incyte lands priority review for PD-1 inhibitor in anal cancer

In a briefing document posted Tuesday ahead of the vote for retifanlimab, ODAC flagged a bevy of concerns with the mid-stage trial.

Just 13 people, or 14%, responded to the treatment out of 94 patients. The trial did not show a durability of response, which clouds the ability to conclude survival benefit, according to the committee.

While the safety profile of retifanlimab appeared similar to what's been recorded with other checkpoint inhibitors in other disease settings, the committee determined that 10 out of 37 deaths were attributed to treatment emergent adverse events, or causes other than disease progression.

In case a reminder is needed—the total trial population was 94.

There were 72 white patients, one Black patient and four Hispanic or Latino participants among multiple unreported races. This could be a major thorn for Incyte, as the committee questioned "how applicable the results" could be to patients who would actually receive retifanlimab, if the drug were to receive approval.

Retifanlimab's 14% overall response rate also did not beat its competitors, even though this cancer tends to be a poor responder anyway. In other small studies, two chemotherapies, Bristol Myers Squibb's Opdivo and Merck's Keytruda have reached a 17% to 33% response. 

Incyte was hoping to reach a 25% response in the phase 2 trial, prompting the FDA in September to question whether this measure could reasonably predict clinical benefit.

Other therapies that have been granted accelerated approval have also done much better on prolonged response compared to retifanlimab's 9.5 months in the 13 responders. 

The study had an insufficient number of patients 65 years or older and too few HIV-positive patients in the small single-arm study, the committee noted. HIV and human papillomavirus are "almost always associated" with this type of anal cancer, Incyte said.

RELATED: 2021 forecast: Clinical trial diversity has long been a thorn in biopharma's side, but 2020 could turn things around

Even though the FDA is not bound to the ODAC recommendation, Mizuho analysts said in a note that they "do not have meaningful expectations given the clinical results and modest patient population," of less than 9,000 new cases annually.

The firm called retifanlimab "a facilitator" for the rest of Incyte's immuno-oncology pipeline, with potential for use in combination therapies. This is likely to occur "later rather than sooner," the Mizuho analysts wrote.

Mizuho kept its rating at neutral as the analysts do not expect a large impact on shares. And indeed, Incyte's stock barely wavered Thursday morning, down less than 1% as of 10:17 a.m. ET.

Retifanlimab was granted an orphan drug tag and priority review by the FDA, with a decision on the application due July 25. 

Lance Leopold, M.D., Incyte's group vice president for immuno-oncology clinical development, said the company is disappointed, but he pledged to work with the FDA as the drug application works its way towards a decision, according to a statement.

This is not Incyte's first rodeo with the FDA on a complex drug approval. The rheumatoid arthritis drug baricitinib, which was developed in partnership with Eli Lilly, hit roadblocks on its way to approval in 2018.