Rocket researcher seeking future gene therapy cures for genetic heart diseases at the company’s … [+]
Cardiovascular diseases are the world’s leading cause of death, responsible for more than 18 million lives lost annually, 700,000 in the US alone. Cardiac disorders can be inherited such as arrhythmias, congenital heart disease, cardiomyopathy, and high blood cholesterol. However, as Dr. Gaurav Shah, CEO of Rocket Pharmaceuticals, likes to say, “DNA is not your destiny.” As a company on a mission to change the lives of millions of people who live with rare genetic diseases, Rocket has quietly transformed itself into a leader in the world of gene therapy, most recently reaching a major milestone for gene therapy and genetic heart disease. Over the last eight years, Shah and Rocket’s President and COO, Kinnari Patel, well-known female leader in science and drug development, along with co-founder Jonathan Schwartz, MD, who is now Chief Gene Therapy Officer, have been at the forefront of driving innovative gene therapy research for devastating and rare life-threatening disorders that have no cure.
Rocket’s innovative R&D approach has resulted in a pipeline of one-time, potentially curative genetic therapies that aim to correct the root cause, meaning at the genetic level, of these complex and often fatal diseases. The pipeline includes six gene therapy programs addressing cardiovascular and hematology-based diseases, each of which has demonstrated positive clinical and/or pre-clinical success. One of Rocket’s programs, RP-A501, is designed to treat patients with Danon Disease, a devastating, uniformly fatal rare genetic heart disorder that either leads to requiring a heart transplantation or facing death during adolescence or early adulthood, with the majority of male patients passing away by the age of 20 and most females by the age of 40. At present, there is no cure or approved treatments that reverse its effects. The condition is caused by mutations in the LAMP2 gene and is estimated to impact between 15,000 and 30,000 people in the U.S. and Europe. The only available treatment option for Danon patients is a heart transplant which is incredibly challenging due to limited donor supply and when received, is associated with substantial complications and is not curative.
Maddie shares her journey living with arrhythmogenic cardiomyopathy caused by PKP2 gene mutations … [+]
RP-A501, however, is a one-time, IV-based gene therapy that seeks to restore normal cardiac function and serves as a cure for patients with Danon Disease. Most of all, it is the first investigational gene therapy for a genetic heart disease known to demonstrate positive results in human studies. The gene therapy involves an infusion of a scientifically designed, non- replicating viral vector that delivers a healthy copy of the therapeutic LAMP2 gene to the affected cells in the heart. Rocket’s RP-A501 trial data showed RP-A501 to be safe in patients treated, and adult and pediatric patients demonstrated improvement or stabilization of their heart-related Danon symptoms with patients also reporting significant improvements in how they function and feel.
Patel has seen the impact gene therapy has had on patients in trials first hand. “There was one child who was so out of breath, he couldn’t even walk. This robbed him of his childhood as he was frequently ostracized for his inability to walk, heavily medicated and was in and out of hospitalization. Within six months of taking the gene therapy he was able to walk for an extended period time allowing him to do normal activities for his age such as trick-or-treating and attending sleepover camps. Seeing these results in under a year was remarkable. His case, along with similar ones, have helped lead to a strong collaborative partnership with the FDA’s CEBR (Center for Biologics Evaluation and Research) division in working towards putting RP- A501 on a regulatory path to approval.”
Rocket executives and renowned scientific collaborators with Dr. Moris Danon, who discovered Danon … [+]
In September of 2023, Rocket reached a major milestone in announcing it reached FDA alignment to initiate a Phase Two pivotal study for RP-A501 for the treatment of Danon Disease, becoming the first gene therapy for the heart to reach this final stage of clinical trial. The study involves 12 patients who will be evaluated over the course of 12 months. Provided continued positive results in this final phase and Rocket moving forward as planned, it would become the first gene therapy for any cardiac condition to be submitted to the FDA for marketing approval. What excites Rocket greatly is not just the potential to cure Danon patients once and for all but the potential of this work in Danon and RP-A501 to open the door to developing cardiac gene therapies for the broader array of inherited heart diseases that affect so many patients, including those that lead to heart failure or stroke. It is already applying learnings to two additional genetic heart diseases (PKP2-ACM and BAG3-DCM). The PKP2-ACM program is already in a Phase 1 clinical study with BAG3-DCM in the pre-clinical phase.
Taken together, these three gene therapy programs targeting the heart not only represent three major forms of heart diseases but have the potential to impact more than 100,000 patients in the U.S. and Europe. Overall, as of today, Rocket has moved three of its gene therapy programs into pivotal Phase Two studies and one program is in review at the FDA for marketing approval. This is regarded by many as a remarkable feat in the field, having taken just five years from human clinical studies to FDA submission of a marketing application in an industry known for development cycles that are much longer. But speed is just one piece of Rocket’s mission, “Moving fast for us, and any biotech, is vital when patients are facing life and death, but pushing gene therapy to help change the trajectory of inherited rare disease has pushed us even harder,” shared Dr. Shah. With the progress on Danon and addressing genetic heart disease, Rocket’s vision for a gene therapy revolution seems upon us.