Rocket Pharmaceuticals' Gene Therapy Shows Promise for Inherited Heart Condition

Rocket Pharmaceuticals has unveiled encouraging early-stage data for its gene therapy targeting plakophilin-2 related arrhythmogenic cardiomyopathy (PKP2-ACM), a rare inherited heart disease. The results, presented at the American Society of Gene and Cell Therapy (ASGCT) conference in New Orleans, suggest a well-tolerated safety profile and potential clinical benefits that analysts believe "set a new bar" for efficacy in treating this condition.

Phase 1 Trial Results

The phase 1 trial, evaluating RP-A601, an AAVrh74-based gene therapy, enrolled three patients who received a single dose of 8.0E13 GC/kg. Key findings from the study include:

• No dose-limiting toxicities reported in patients followed for up to 12 months
• Most treatment-emergent adverse events were mild or moderate
• One patient experienced severe adverse events that resolved within two months, likely related to the immunosuppression regimen
• All patients showed elevated liver enzyme levels

Efficacy data demonstrated improvements in arrhythmia burden and normalization of myocardial structure. Notably, two patients progressed from New York Heart Association (NYHA) class II to class I, indicating no clinical signs of heart failure. Right ventricular systolic function remained stable in all three patients, and cardiac biopsies revealed increased PKP2 protein expression.

Analyst Perspectives and Future Outlook

William Blair analysts view the initial data as validating the safety, efficacy, and transduction efficiency of the selected dose. They suggest that these results could provide a foundation for discussions regarding an accelerated approval pathway.

However, the analysts noted that RP-A601 uses the same vector as Sarepta's Elevidys, which was recently associated with a patient death in a separate trial. This observation underscores the importance of a conservative approach to immunosuppression in gene therapy trials.

Next Steps for Rocket Pharmaceuticals

Given the promising activity at the current dose, Rocket has decided against future dose escalation. The company is now assessing potential next steps, including the design of a pivotal trial. RP-A601 has already received fast-track and orphan drug designations from the FDA, highlighting its potential as a curative treatment for PKP2-ACM.

Rocket CEO Gaurav Shah, M.D., expressed optimism about the preliminary data, stating that it signals "potential clinical benefit along with a generally well-tolerated safety profile."

As the pharmaceutical industry continues to explore gene therapies for rare diseases, Rocket's RP-A601 represents a significant step forward in addressing the underlying genetic mutation of PKP2-ACM, potentially offering hope to patients with limited treatment options.