FDA Torpedoes CytoDyn's Leronlimab for COVID-19 with Rare Public Scolding

FDA_Al Drago/CQ Roll Call

Al Drago/CQ Roll Call

The U.S. Food and Drug Administration (FDA) published a “Statement on Leronlimab,” CytoDyn’s monoclonal antibody that was initially being developed for HIV and cancer before it began testing for COVID-19. In unusual public scolding, the agency accused the company of misrepresenting its clinical trial results for the drug in COVID-19. 

In particular, the statement focused on results from two clinical trials, CD10, in 86 mild-to-moderate COVID-19 patients, and CD12, which included 394 patients, focused on severe symptoms of respiratory symptoms associated with COVID-19.

In March, CytoDyn’s Phase III trial of leronlimab, a CCR5 antagonist, failed to hit the primary endpoint of reducing symptoms and missed all secondary endpoints, including if the drug decreased mortality for COVID-19. However, the company placed a positive spin, focusing on a subgroup of 62 patients on mechanical ventilation, arguing that leronlimab caused a 24% decrease in all-cause mortality and a six-day reduction in hospitalization. They then released a second press announcement describing an “age adjustment” analysis alleging leronlimab decreased mortality in older patients.

The FDA stated, “It has become clear that the data currently available do not support the clinical benefit of leronlimab for the treatment of COVID-19. None of these analyses met statistical significance when using established and reliable analytical methods that correct for multiple comparisons.”

Investors were paying attention, and company shares plunged more than 27%. Also, in a recent 10-Q filing, a shareholder has filed a class-action lawsuit against the company, alleging it made false and misleading statements about how effective leronlimab is for treating in COVID-19. A second lawsuit along the same lines was filed in April.

The FDA’s rebuke is rare. They noted, “Although FDA generally cannot disclose confidential information about unapproved products, we have concluded that given the significant public interest in leronlimab, it is important to provide summary information about the status of the CytoDyn development program.”

The agency then described what a well-designed clinical trial is and how that differs from what CytoDyn was doing. For example, “If the analyses of the primary and secondary endpoints do not support conclusions of the medicine’s benefit, then FDA considers subgroup analyses to be exploratory, meaning they may inform the design of future trials, but do not support reliable conclusions about the medicine’s benefit. Focusing on only the most favorable of many subgroup analyses, even if the subgroups 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.”

In what seems to be a summary remark, but which was in the middle of the FDA statement, the agency said, “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.”

The agency did say that if CytoDyn planned additional studies of leronlimab for COVID-19, the agency would continue to provide advice. In addition to COVID-19, CytoDyn is evaluating the drug for HIV, a broad range of solid tumors, psoriasis and Crohn’s disease, graft versus host disease, and nonalcoholic fatty liver disease.

Today, CytoDyn announced they planned to submit the results of the newly completed topline data of its CD12 Phase III trial to various regulatory agencies, including but not limited to regulators in India and the Philippines. 

“We are very thankful for the opportunity to be able to conduct two very crucial clinical trials in Brazil for severe and critically ill COVID-19 patients, which we believe could result in a statistically significant p-value of our primary endpoint leading the way to a potential approval,” stated Nader Pourhassan, president and chief executive officer of CytoDyn. “Although we did not meet our primary endpoint in our CD12 clinical trial in the mITT population, we were still very pleased that we did meet almost all of our secondary endpoints in the critically ill subpopulation of COVID-19 patients. To the best of our knowledge, we are unaware of another drug or therapeutic which has reported results in the critically ill population, in a random controlled trial, remotely close to what we reported for the CD12 trial. We are very excited for the opportunity to receive our first approval in multiple countries in great need of leronlimab. We are very confident this approval will happen this year.”

The company also recently inked an agreement for a possible emergency authorization and compassionate use program for the drug in India. And on May 7, it announced plans to launch two clinical trials in Brazil.

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