In an unprecedented public rebuke, the FDA accused CytoDyn of trying to cherry-pick data from two failed studies of leronlimab in COVID-19 patients to claim the drug is effective.
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.”
Shares of CytoDyn plummeted when the FDA released its statement just before the market closed. The stock lost 76 cents in value, dropping more than 27% to $2.04 at market close.
The FDA is not the only one to have noticed CytoDyn’s missteps. 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 U.S. 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.
A request for comment to CytoDyn went unreturned as of publication.
As recently as last week, CytoDyn signed a deal to pursue an emergency authorization and compassionate use program for leronlimab in India. Another deal to start two clinical trials in Brazil was announced May 7.
The FDA said the subgroup analyses could be used to form the basis of future trials and pledged to work with CytoDyn should the company wish to move forward with new research in COVID-19.
Outside of COVID-19, CytoDyn is trialing 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.