AHA24: Rocket's gene therapy shows promise in five-year data for rare heart disorder

Rocket Pharmaceuticals has reported promising long-term safety and efficacy outcomes from an early-stage study of its gene therapy RP-A501 for Danon disease, a rare genetic disorder linked to mutations in the LAMP-2 gene. These results were unveiled at the American Heart Association’s scientific sessions and published in the New England Journal of Medicine, showcasing benefits lasting up to 60 months after a single treatment.

Danon disease, an X-linked inherited condition, has severe implications due to mutations in the LAMP-2 gene. Rocket Pharmaceuticals' CEO, Gaurav Shah, emphasized that this program provides the most comprehensive investigational gene therapy data for any cardiac condition. Shah also suggested that their gene therapy platform has potential applications for other inherited heart diseases, including PKP2-arrhythmogenic cardiomyopathy and BAG3-dilated cardiomyopathy.

The Phase I study involved seven male patients with Danon disease, with five receiving a low dose and two a high dose of RP-A501. The results indicated that pediatric participants experienced sustained, clinically significant improvements for up to 24 months, while adult and adolescent participants showed benefits for up to 60 months. All patients who could be evaluated showed cardiac LAMP2 protein expression within 12 months. There was a median 24% reduction in left ventricular (LV) mass index from baseline, maintenance of normal LV ejection fraction, and notable stabilization or decrease in cardiac biomarkers. Additionally, quality-of-life scores improved by a median of 27 points, and the New York Heart Association (NYHA) heart failure class improved from Class II to Class I. One patient exhibited Grade 3 protein expression at five years, underscoring the long-term efficacy of the therapy.

Regarding safety, the gene therapy was generally well-tolerated, with most adverse events being mild or moderate and manageable or reversible. However, one patient with severe pre-existing heart failure required a heart transplant five months post-treatment due to disease progression. Principal investigator Barry Greenberg stated that the study found consistent and significant improvements across multiple quantifiable measures used by cardiologists to assess risk and make treatment decisions.

In September, Rocket Pharmaceuticals announced alignment with the FDA concerning a pivotal Phase II trial to support the accelerated approval of RP-A501 for Danon disease. This announcement positively impacted the company's stock, which surged by up to 42%. At the time, Needham analyst Gil Blum predicted that the gene therapy could become a significant value driver due to the size of the patient population and the absence of available therapies.

In summary, Rocket Pharmaceuticals' RP-A501 gene therapy for Danon disease has demonstrated long-lasting safety and efficacy, with potential implications for other inherited heart conditions. The Phase I study results are encouraging, showing sustained clinical improvements and manageable safety profiles, paving the way for further development and potential FDA approval.