FDA halts gene therapy for rare heart disease

Rocket Science?

The Food and Drug Administration (FDA) put a temporary stop to an early-stage trial of an experimental Rocket Pharmaceuticals gene therapy for a rare and deadly heart condition, Danon disease, reported Ben Fidler, senior editor of BioPharma Dive. Instead of halting testing because of a safety issue, the FDA  asked Rocket to put "additional risk mitigation methods" into its clinical program. This action could signal possible changes to enrollment criteria or drug regimens that might go along with treatment with the gene therapy.

Fidler related that the clinical hold is “the latest in a string of regulatory setbacks for gene therapies due to safety or manufacturing concerns.” He also described it as “the first bump in the road for Rocket's Danon program, a key driver of the biotech's recent stock surge.” Rocket said that it expects to resolve the issue with no more than a three-month delay to study enrollment.

Since its founding in late 2015 by former Novartis and Eli Lilly veterans, Rocket has become one of the most valuable gene therapy developers that are still independent. While the company targets diseases that affect very small groups of patients, its pipeline is broad. Clinical data that may come out this year could determine the company’s future.

Fidler said that early data on Rocket’s gene therapy for Danon, a deadly disease with no approved treatments, were a big reason for Rocket’s valuation on Wall Street. Danon involves weakness of the heart and skeletal muscles and leads to cognitive impairment, cardiomyopathy and often heart transplants. Men who have the disease die at around 19 years of age. About 15,000 to 30,000 people in the U.S. and European Union have the disease.

Gene therapy from Rocket aims to restore cardiac function. Results from early testing have demonstrated a decline in markers of heart failure in a small group of young adult patients. While no gene therapy has been proven as yet to successfully treat a cardiovascular condition, Rocket results Rocket have shown some promise, with evidence of "stabilization and even some modest improvements," according to Rocket CEO Gaurav Shah. However, one patient on a higher dose had an adverse effect last year, prompting more safeguards. Although there have been no new adverse events related to the therapy, the FDA halted dosing and asked for new risk mitigation measures. The agency asked that Rocket enroll patients who are younger and whose disease is not as advanced and that Rocket "further refine and enhance" the safety measures in its trial design. The company didn't provide specifics, though chief medical officer Jonathan Schwartz noted a more "rigorous, preemptive use" of drugs like Soliris "may be in the offing."

Rocket believes it can quickly resolve the situation. Shah predicted that enrollment would only be delayed by a quarter, because it is not a manufacturing issue or a request for additional data that would otherwise result in a prolonged delay. Shares fell by as much as 25 percent before trading down roughly 15 percent early in May. While some analysts think the delay might be longer than Rocket estimated, other analysts expect little disruption as Rocket addresses the safety concerns by treating younger patients with a lower dose.