PKP2-Arrhythmogenic Cardiomyopathy Gene Therapy Nets Fast Track, Orphan Drug Designations
Rocket Pharma is working to soon initiate a phase 1 trial of RP-A601.
The FDA has granted Fast Track and Orphan Drug designations to Rocket Pharmaceuticals’ RP-A601 gene therapy for the treatment of plakophilin-2 relatedArrhythmogenic Cardiomyopathy (PKP2-ACM).1
RP-A601 is an adeno-associated virus vector (AAV.rh74) gene therapy. Rocket announced that its investigational new drug application (IND) for the therapy was cleared by the FDA in May 2023 based on preclinical studies that demonstrated decreased arrhythmias and increased survival.2 RP-A601 is the first gene therapy in development for PKP2-ACM to receive IND clearance.
Following the news of IND clearance, Rocket announced that it would be initiating a phase 1 dose escalation trial to assess the preliminary safety and efficacy of RP-A601 in at least 6 patients with PKP2-ACM with implantable cardioverter defibrillators (ICDs) and high risk for serious arrhythmias. The trial will also assess PKP2 myocardial protein expression, cardiac biomarkers, sudden cardiac death, and clinical predictors of life-threatening ventricular arrhythmias. The starting dose will be 8 x 1013 GC/kg.
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“Today’s news is a significant milestone, as we build on our leading cardiovascular gene therapy expertise to advance a historic second program targeting the heart into clinical development, this time for patients with PKP2-ACM who have an urgent need for improved treatment options,” Kinnari Patel, PharmD, MBA, president and chief operating officer, Rocket Pharma, said in a statement at that time.2 “RP-A601 offers the potential of a one-time, curative alternative to medical therapy, ICDs, and ablations which are associated with adverse effects, complications, and recurrence of arrhythmias and do not halt the progression of disease. Robust preclinical proof of concept has demonstrated decreased arrhythmias and increased survival. With IND clearance in hand, we are rapidly advancing the first investigational gene therapy for PKP2-ACM into the clinic.”
PKP2-ACM is an inherited heart disease that affects approximately 50,000 people in the United States and Europe and can lead to life-threatening arrhythmias, cardiac structural abnormalities, and sudden cardiac death. The current standard of care includes medical therapy, ICDs, and ablations, which are not curative and may not prevent life-threatening arrhythmias and progression of disease.
Rocket has racked up quite a few FDA designations in the last couple of months, with the company’s RP-A501 gene therapy for Danon disease receiving Priority Medicines (PRIME) designation from the European Medicines Agency and its RP-L301 gene therapy for pyruvate kinase deficiency receiving regenerative medicine advanced therapy (RMAT) designation from the FDA in May 2023.3,4
