Rocket Pharmaceuticals Maxes Out Recruitment in Pivotal Trial for Danon Disease Gene Therapy RP-A501

Rocket Pharmaceuticals has finished enrolling all patients in a pivotal phase 2 clinical trial (NCT06092034) evaluating RP-A501, an investigational adeno-associated virus vector-based gene therapy, for the treatment of Danon disease.¹

The single-arm trial enrolled 12 male patients in total across the United States and European Union, and all patients received a dose of 6.7x10¹³ GC/kg of the gene therapy. The first 2 patients were enrolled as part of a pediatric safety run-in, which utilized sequential enrollment and required at least 3 months of follow-up before further recruitment. Improvements in expression of LAMP2, the disease-targeted protein, serves as 1 of 2 primary end points for the study, alongside the observed decrease in left ventricular mass. Among the study’s secondary end points are a key secondary end point for the change in troponin levels and additional end points for natriuretic peptide levels, event free survival up to 24 months, treatment-emergent safety events, New York Heart Association (NYHA) class, and responses on the Kansas City Cardiomyopathy Questionnaire. The results will be compared to findings from a global natural history study that the company is carrying outsimultaneously.^1,2 Rocket stated that it intends to seek regulatory filings for RP-A501 inside and outside the US concurrently.

“From a clinical perspective, the important thing is that we are moving closer to the goal of having a treatment for patients with Danon disease,” Barry H. Greenberg, MD, FHFSA, the director of the Advanced Heart Failure Treatment Program and a distinguished professor of medicine at UC San Diego Health, said in a statement.¹ “I can attest to the excitement and anticipation within the Danon patient community for this novel, one-time treatment designed to improve cardiac abnormalities associated with Danon disease and help preserve normal cardiac function by delivering functional LAMP2B genes to the heart tissue. The rapid recruitment of the phase 2 trial signifies the positive views of the study clinicians regarding this investigational therapy.”

RP-A501 was previously evaluated in a phase 1 clinical trial (NCT03882437) for patients with Danon disease. A coprincipal investigator of that trial, Joseph Rossano, MD, MS, FAAP, FACC, the chief of the Division of Cardiology at Children's Hospital of Philadelphia, is also serving as coprincipal investigator of the phase 2 study. In 2022, CGTLive® interviewed Rossano about the potential of gene therapy in Danon disease.

“Potentially, a gene therapy for this disorder can be a real game changer,” Rossano said in the interview. “In the current state, there really is no effective medical therapy. We have medicines that can hopefully help treat symptoms of heart failure and can treat arrhythmias. But we have no therapies that alter the natural history of the disease. And so what's really exciting about this therapy is that it offers the prospect and the hope of dramatically changing the natural history.”

In addition to RP-A501, Rocket is developing several other advanced therapeutics. Notably, the FDA accepted a biologics license application with priority review in October 2023 for marnetegragene autotemcel (RP-L201, to be marketed as Kresladi), Rocket’s genetically-modified autologous hematopoietic stem cell therapy intended to treat leukocyte adhesion deficiency-I (LAD-I).^3,4 In June 2024, the agency issued a complete response letter (CRL) regarding Kresladi with a request for more Chemistry Manufacturing and Controls (CMC) information to complete its review. The CRL marks the second time the FDA has requested more CMC information, after the agency extended its priority review for Kresladi, pushing back the therapy’s Prescription Drug User Fee Act date from March 31, 2024, to June 30 to allow additional time to review clarifying information submitted by Rocket in response to FDA information requests.⁵

REFERENCES
1. Rocket Pharmaceuticals announces completion of enrollment in phase 2 pivotal trial of RP-A501 for the treatment of Danon disease. News release. September 17, 2024. Accessed September 19, 2024. https://ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-announces-completion-enrollment-phase-2
2. Rocket Pharmaceuticals reaches FDA alignment on pivotal phase 2 trial design for RP-A501 in Danon disease. News release. Rocket Pharmaceuticals, Inc. September 12, 2023. Accessed September 19, 2024. https://ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-reaches-fda-alignment-pivotal-phase-2
3. Rocket Pharmaceuticals announces FDA acceptance of biologics license application with priority review for RP-L201 (marnetegrageneautotemcel) for the treatment of severe leukocyte adhesion deficiency-I (LAD-I). News release. Rocket Pharmaceuticals. Accessed September 19, 2024. https://www.biospace.com/article/releases/rocket-pharmaceuticals-announces-fda-acceptance-of-biologics-license-application-with-priority-review-for-rp-l201-marnetegragene-autotemcel-for-the-treatment-of-severe-leukocyte-adhesion-deficiency-i-lad-i-/
4. Rocket Pharmaceuticals Provides Regulatory Update on KRESLADI™ (marnetegragene autotemcel; marne-cel). News release. Rocket Pharmaceuticals. June 28, 2024. Accessed September 19, 2024. https://finance.yahoo.com/news/rocket-pharmaceuticals-provides-regulatory-kresladi-112700392.html
5. Rocket Pharmaceuticals Announces Update on FDA Review Timeline of KRESLADI™ (marnetegragene autotemcel) for the Treatment of Severe Leukocyte Adhesion Deficiency-I (LAD-I). News release. Rocket Pharmaceuticals. February 13, 2024. Accessed September 19, 2024. https://www.biospace.com/article/releases/rocket-pharmaceuticals-announces-update-on-fda-review-timeline-of-kresladi-marnetegragene-autotemcel-for-the-treatment-of-severe-leukocyte-adhesion-deficiency-i-lad-i-/