- The Food and Drug Administration has temporarily halted an early-stage trial of an experimental Rocket Pharmaceuticals gene therapy for a rare and deadly heart condition known as Danon disease.
- The news came as somewhat of a surprise, as the agency didn't stop testing due to a new safety issue. Rather, the FDA asked Rocket to put "additional risk mitigation methods" into its clinical program, which executives on a conference call described as potential changes to enrollment criteria or drug regimens that would accompany treatment with the gene therapy.
- The clinical hold is the latest in a string of regulatory setbacks for gene therapies due to safety or manufacturing concerns. It also marks the first bump in the road for Rocket's Danon program, a key driver of the biotech's recent stock surge. Rocket believes, however, that it can resolve the issue with no more than a three-month delay to study enrollment.
Over the past year, Rocket has grown to become one of gene therapy's most valuable independent companies, with a relatively broad pipeline of rare disease treatments and a market capitalization eclipsing more established companies like Bluebird Bio and UniQure.
Early data supporting its gene therapy for Danon — a deadly disease with no approved treatments for its underlying cause — are a large component of that rise. The disease is characterized by weakness of the heart and skeletal muscles, and leads to cognitive impairment, cardiomyopathy and often heart transplants. Males with the disease, on average, die at 19 years of age. Rocket estimates there are between 15,000 to 30,000 people with Danon in the U.S. and European Union.
Rocket's gene therapy is meant to restore cardiac function. Early testing has so far shown a decline in markers of heart failure among a small group of young adult patients.
It's unclear whether these effects will lead to improved function and health outcomes. No gene therapy has been proven to successfully treat a cardiovascular condition. Still, updated results Rocket disclosed from two patients treated with a low dose 18 months ago showed some promise, with evidence of "stabilization and even some modest improvements," where natural history would suggest these patients would decline further, said CEO Gaurav Shah, on a conference call.
Last year, Rocket did disclose one patient on a higher dose had an immune response that had to be treated with Alexion Pharmaceuticals' drug Soliris. That led Rocket to more closely monitor patients and increase safeguards, and there haven't been any new adverse events related to the therapy disclosed since. Rocket executives said that just as the company was preparing to treat a new cohort of pediatric patients last week, the agency halted dosing and asked for new risk mitigation measures to be put in place.
The requests fell into "two buckets," Shah said. One involves patient eligibility; Rocket needs to enroll patients who are younger and whose disease isn't as advanced. The other is to "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. "This is not a [manufacturing] issue, it is also not a request for additional data that would otherwise result in a prolonged delay to the program," Shah said, predicting enrollment would only be delayed by a quarter.
Shares still fell by as much as 25% before trading down roughly 15% post-market close on Monday. It's "formally possible that the unpredictable and conservative FDA may translate to a longer-than-expected delay," wrote Stifel analyst Dae Gon Ha. Multiple gene therapy studies have been paused over the past year, and the agency is viewed as having taken a stricter approach in recent drug decisions.
But both Dae Gon Ha and SVB Leerink analyst Mani Foroohar expect little disruption for Rocket going forward. Foroohar, for instance, believes safety concerns should be mitigated as Rocket treats younger patients with a lower dose.