Rocket Pharmaceuticals (NASDAQ:RCKT) outlined updated clinical, regulatory and commercial plans for its investigational gene therapy RP-A501 in Danon disease, reporting longer-term Phase I findings, preliminary Phase II observations and an FDA-aligned pivotal study design.
Chief Executive Officer Gaurav Shah said the company’s existing resources and an initial $35 million funding under a new Hercules facility are expected to support operations into the third quarter of 2028. Subject to borrowing conditions, additional draws could extend the cash runway into 2029, he said.
Phase I Data Show Long-Term Protein Expression
Rocket reported that six evaluable Phase I patients demonstrated myocardial LAMP2 expression at or above grade 1 and at least a 10% reduction in left ventricular mass index, or LVMI, at approximately 12 months. The company said five of the six patients remained transplant-free at the latest follow-up, while one patient underwent cardiac transplantation about 4.8 years after treatment.
Follow-up in the Phase I program extended from 4.3 to 7.1 years. Rocket said two pediatric patients showed robust LAMP2 expression at 36 months, and one patient continued to show robust expression at 60 months. At the latest imaging evaluations, LVMI remained below baseline in five of six evaluable patients, including reductions of at least 10% in four patients.
Shah said biomarkers including NT-proBNP and troponin were reduced from baseline in all six patients at their latest follow-up. Five of the six were asymptomatic for heart-failure symptoms after improving from New York Heart Association Class II to Class I, while one remained in Class II.
Dr. Jonathan Schwartz, Rocket’s chief science and gene therapy officer, said the company was still gathering information on the patient who received a transplant. He noted that the patient had a substantial arrhythmic component to the disease presentation and had experienced improvement in several measures and symptom resolution in the years following treatment.
Modified Phase II Protocol Addresses Safety Events
The company also discussed serious safety events in earlier Phase II cohorts. Two of the first four Phase II patients experienced thrombotic microangiopathy, or TMA. Rocket subsequently added a C3 inhibitor to the immunomodulatory regimen for two additional patients, but both experienced severe adverse events including capillary leak syndrome, and one patient died.
Chief Medical Officer Syed Rizvi said Rocket paused treatment and performed a root-cause analysis. The company concluded that C3 inhibition may have reduced opsonization of AAV and increased uptake by vascular endothelial cells, contributing to vascular injury.
Following discussions with FDA, the independent data monitoring committee and external experts, Rocket removed the C3 inhibitor, reduced the dose and expanded monitoring. The revised regimen includes three doses of rituximab rather than two, screening for predisposition to TMA, and specified intervention thresholds, including use of eculizumab.
Three patients have now received the recalibrated dose of 3.8 x 1013 genome copies per kilogram, compared with 6.7 x 1013 genome copies per kilogram used in the earlier Phase II cohorts. As of a Sept. 4, 2026 data cutoff, the three patients had completed their initial observation periods without clinical or laboratory evidence of TMA, capillary leak syndrome or other severe complement-mediated toxicities, according to the company.
Rizvi said one patient experienced a transient platelet decrease at approximately weeks eight to nine, which resolved and was not considered clinically significant by the investigator or sponsor. FDA and the independent data monitoring committee subsequently confirmed that enrollment and dosing could continue under the modified protocol.
Pivotal Study Targets Seven Responders
Rocket said FDA agreed that its pivotal Phase II efficacy population will consist of 12 male patients receiving commercial-grade RP-A501 at the recalibrated dose. The study is a global, single-arm, open-label registrational trial.
The efficacy target is at least seven of 12 patients meeting both responder criteria at 12 months:
- Myocardial LAMP2 protein expression of at least grade 1; and
- At least a 10% reduction in LVMI from baseline.
The first three patients treated under the modified protocol count toward the pivotal population, leaving nine additional patients to be enrolled and dosed. Rocket expects to complete dosing by mid-2027. Shah said the company intends to use the 12-month data as the primary efficacy basis for a biologics license application seeking accelerated approval and priority review, though any approval would depend on FDA’s overall benefit-risk assessment.
Commercial Estimates and Patient Identification
Chief Commercial Officer Sarbani Chaudhuri said two epidemiology analyses—one based on genotype and one on clinical phenotype—each estimated that approximately 10,000 to 11,000 people in the U.S. may have Danon disease, including about 4,000 males and 6,000 to 7,000 females. The company estimated more than 20,000 people may be affected across the U.S. and EU5.
Rocket said it has identified more than 900 patients with confirmed Danon diagnoses across approximately 300 U.S. institutions, though that cumulative count includes people who may have received transplants or died. The company said the top 100 institutions account for about 60% of identified patients.
Chaudhuri said Rocket estimates the initial indication in males with hypertrophic cardiomyopathy could support more than $1 billion in global peak annual revenue, contingent on clinical success, regulatory approval, diagnosis rates, treatment eligibility and access. The company said potential future expansion into additional male and female populations could raise the estimated global peak opportunity above $2 billion.
About Rocket Pharmaceuticals (NASDAQ:RCKT)
Rocket Pharmaceuticals, Inc (NASDAQ:RCKT) is a biotechnology company focused on developing gene therapies for rare and devastating diseases. The company uses both ex vivo hematopoietic stem cell gene therapy and in vivo adeno-associated virus (AAV) gene therapy approaches to address conditions with limited or no effective treatment options.
Rocket’s development programs have included marnetegragene autotemcel (RP-L102) for leukocyte adhesion deficiency-I, a rare inherited immune disorder; RP-A501 for Danon disease, a genetic heart condition; RP-A601 for arrhythmogenic right ventricular cardiomyopathy associated with PKP2 mutations; and RP-L301 for pyruvate kinase deficiency, an inherited blood disorder.
