21 June 2019 - - Patient dosing has commenced in the open-label, Phase 1 clinical trial of RP-A501, US-based multi-platform clinical-stage gene therapy company Rocket Pharmaceuticals, Inc.'s (NASDAQ: RCKT) adeno-associated viral vector -based gene therapy for the treatment of Danon disease, the company said.
University of California San Diego Health is the initial and lead center for the Phase 1 clinical trial under a leadership of Eric Adler, M.D., director of Cardiac Transplant and Mechanical Circulatory Support at UC San Diego Health and Professor of Medicine at University of California, San Diego School of Medicine and Barry Greenberg, M.D. Dr. Greenberg is the director of the Advanced Heart Failure Treatment Program at UC San Diego Health and Professor of Medicine at UC San Diego School of Medicine, and is principal investigator of the trial.
The non-randomised, open-label Phase 1 trial is expected to enroll 12-24 pediatric and young adult male patients. Two dose levels will be investigated in four patient cohorts separated by pediatric and adult age groups.
The first cohort will receive a low dose level of 6.7x1013 genome copies/kg.
Upon completion of patient dosing at the low dose, the company plans to move to a higher dose. The study is designed to assess the safety and tolerability of a single infusion of RP-A501.
Additional outcome measures include cardiomyocyte and skeletal muscle transduction by gene expression, histologic correction via endomyocardial biopsy, and clinical stabilisation via cardiopulmonary testing.
Danon disease is caused by mutations in the gene encoding lysosome-associated membrane protein 2 (LAMP-2), an important mediator of autophagy. It is estimated to have a prevalence of 15,000 to 30,000 patients in the US and the European Union.
The disease is often fatal in male patients in the second or third decade of life due to rapidly progressive heart failure. Available therapies for Danon disease include cardiac transplantation, which is associated with substantial complications and is not considered curative.
There are no specific therapies available for the treatment of Danon disease.
Rocket Pharmaceuticals is an emerging, clinical-stage biotechnology company focused on developing first-in-class gene therapy treatment options for rare, devastating diseases.
Rocket's multi-platform development approach applies the well-established lentiviral vector and adeno-associated viral vector gene therapy platforms.
Rocket's first two clinical programs are a LVV-based gene therapy for the treatment of Fanconi Anemia, a difficult to treat genetic disease that leads to bone marrow failure and potentially cancer, and an AAV-based gene therapy for Danon disease, a devastating, pediatric heart failure condition.
Rocket's pre-clinical pipeline programmes for bone marrow-derived disorders are for Pyruvate Kinase Deficiency, Leukocyte Adhesion Deficiency-I (LAD-I) and Infantile Malignant Osteopetrosis.