In an unprecedented public rebuke, the US Food and Drug Administration accused drugmaker CytoDyn of trying to cherry-pick data from two failed studies of leronlimab in COVID-19 patients to claim the drug is effective, reports FierceBiotech.
Back in March, a phase 3 clinical trial of CytoDyn’s leronlimab failed on the primary goal of reducing symptoms and all secondary goals, including one that questioned whether the therapy could reduce mortality. But the company instead focused its data release on a subgroup of 62 mechanically ventilated, critically ill COVID-19 patients, claiming that the drug spurred a 24% reduction in all-cause mortality and a six-day reduction in hospitalization, among other trial wins.
CytoDyn then issued a second press release after performing an “age adjustment” analysis that claimed to show leronlimab reduced mortality in older patients.
Now, the FDA has broken its usual vow of silence on disclosing information on unapproved products to say that CytoDyn’s reshaping of the data is erroneous.
“It has become clear that the data currently available do not support the clinical benefit of leronlimab for the treatment of COVID-19,” the FDA said. “None of these analyses met statistical significance when using established and reliable analytical methods that correct for multiple comparisons.”
According to the company’s most recent 10-Q (PDF), a stockholder has filed a class action lawsuit alleging that CytoDyn made false and misleading statements about the viability of leronlimab in treating COVID-19. A second, similar suit was filed in April.
The US regulatory authority went on to explain how clinical trials actually work: A prespecified endpoint is selected, the trial is conducted, and, if the goal is not met, the trial is considered a failure. Any so-called “subgroup” analysis following a failed trial are considered by the FDA to be exploratory and can be used only to inform the design of future trials.
“Focusing on only the most favorable of many subgroup analyses, even if the sub-groups are pre-specified, can lead to overestimating the evidence of benefit, because regardless of a drug’s true efficacy, some analyses are likely to appear favorable by chance when a large number of analyses are conducted,” the FDA said.
After two clinical trial readouts, the FDA has therefore found its answer on leronlimab: “With the conclusion of both the CD10 and CD12 clinical trials, it has become clear that the data currently available do not support the clinical benefit of leronlimab for the treatment of COVID-19.”
In the CD10 trial, the FDA said the data appeared to show that patients recovered from COVID-19 regardless of whether they received leronlimab or placebo. As for the larger CD12 trial, the agency said the drug failed to show any effect on the primary endpoint when compared with placebo.
The FDA said the unusual statement was released because of “significant public interest” in the drug.
Outside of COVID-19, CytoDyn is trialling leronlimab in everything but the kitchen sink including HIV, 22 different solid tumor cancers, autoimmune diseases such as psoriasis and Crohn’s disease, graft-versus-host disease and nonalcoholic fatty liver disease.
Full FierceBiotech report (Open access)
Full FierceBiotech report (Open access)
Full FDA statement on leronlimab (Open access)
See also from the MedicalBrief archives:
FDA grants fast-track status to leronlimab as treatment for HIV and breast cancer