Rocket Pharmaceuticals has shared early data from three patients that tie its gene therapy for an inherited heart disease to a well-tolerated safety profile, which has been heralded by analysts as setting “a new bar” for efficacy in the condition.
The biotech shared initial phase 1 data for RP-A601, an AAVrh74-based gene therapy designed to treat plakophilin-2 related arrhythmogenic cardiomyopathy (PKP2-ACM), at the American Society of Gene and Cell Therapy (ASGCT) conference in New Orleans.
The single-arm, open-label trial is evaluating preliminary safety and tolerability in patients with PKP2-ACM who received one 8.0E13 GC/kg dose of the gene therapy.
No dose-limiting toxicities were reported in three patients followed for up to 12 months, and most treatment-emergent adverse events were mild or moderate in severity, according to the New Jersey biotech.
One patient experienced severe adverse events that resolved within two months of treatment and were thought to be tied to the immunosuppression regimen. All patients experienced elevated liver enzyme levels, Rocket noted.
The preliminary data also demonstrate improvements in arrhythmia burden and normalization of myocardial structure. Notably, two patients achieved a New York Heart Association (NYHA) class I—which means no clinical signs of heart failure are observed—at 12 and six months. The patients had a baseline of NHYA class II, or heart failure that slightly limits activity.
Additionally, right ventricular systolic function was stable in all three patients. Cardiac biopsies also revealed increased PKP2 protein expression, a gene that, when mutated, causes PKP2-ACM.
“Preliminary data from the phase 1 study of RP-A601 for PKP2-ACM are highly encouraging, signaling potential clinical benefit along with a generally well-tolerated safety profile,” Rocket CEO Gaurav Shah, M.D., said in a May 15 release.
Analysts with William Blair agreed, writing in a May 16 note that the initial data validate the safety, efficacy and transduction efficiency of the selected dose.
“Altogether, we believe the early data sets a new bar for PKP2-ACM in terms of efficacy,” the analysts wrote, adding that the data could provide “a foundation for the company to have discussions regarding an accelerated approval pathway.”
While the analysts deemed the safety data “highly encouraging,” they did note that the Rocket therapy uses the same vector as Sarepta’s Elevidys, which was recently tied to the death of a 16-year-old patient with Duchenne muscular dystrophy. As a result, the analysts suggested “a conservative approach with immunosuppression is justified.”
Rocket has discarded plans for future dose escalation given the activity at the current dose, according to the company. The biotech is now assessing possible next steps, including a pivotal trial design.
RP-A601 is being tested as a potentially curative treatment for the heart condition, which is associated with life-threatening ventricular arrhythmias and cardiac death. Current treatments don't consistently prevent disease progression or arrhythmia recurrence, and also don't tackle the genetic mutation underlying the disease, according to Rocket.
The gene therapy has snared both fast-track and orphan drug tags from the FDA.