Patient dies in Rocket Pharmaceuticals’ Phase II Danon disease gene therapy trial (2025)
A patient has died in a pivotal Phase II trial of Rocket Pharmaceuticals’ gene therapy for Danon disease after suffering a serious adverse event (AE).
Rocket said that the patient received a dose of RP-A501 in the Phase II study (NCT06092034) and experienced clinical complications related to capillary leak syndrome. The patient later died after suffering an acute systemic infection.
Rocket Pharmaceutical CEO Dr Gaurav Shah said: “We are heartbroken by this loss and are fully committed to our mission to develop gene therapies that address the underlying cause of devastating diseases like Danon. We are immensely grateful for the patients and families who participate in this important research.”
Following the 27 May announcement, Rocket Pharmaceuticals’ stock, listed on the Nasdaq exchange, opened 63.32% lower than its close on 23 May.
William Blair healthcare analyst, Dr. Sami Corwin, said this drop is likely due to investors being hesitant about the programme’s safety and time to clinical hold resolution.
The US Food and Drug Administration (FDA) placed a clinical hold on the trial on 23 May, by which point Rocket had already paused dosing in the study. The pharmaceutical company is investigating the root cause of the AE and speaking with both the FDA and other key stakeholders.
Rocket said its current focus is the recent introduction of a novel immune suppression agent, a C3 inhibitor, to the pre-treatment regimen that had been implemented to mitigate complement activation seen in certain patients. This agent is specific to the Danon programme.
Corwin said: “The C3 inhibitor was administered pre- and post-RP-A501 treatment in combination with the enhanced prophylactic immunosuppressive regimen of sirolimus, rituximab, and prednisone. In addition, one other patient also received the modified immunosuppression regimen including the C3 inhibitor and also exhibited early signs of capillary leak syndrome but had a reduced course, further supporting the hypothesis that the compound played a role in the development of capillary leak syndrome.”
Rocket is also working with the FDA, the Independent Data Safety Monitoring Committee (IDSM), clinical investigators, and scientific experts to ensure the safety of all study patients, with hopes to resume the study when possible.
Danon disease is a rare, X-linked disorder caused by mutations in the lysosome-associated membrane protein 2 isoform B (LAMP2 gene). Symptoms include hypertrophic cardiomyopathy, skeletal muscle weakness, and intellectual disability.
RP-A501 is an adeno-associated virus serotype 9 (AAV9) gene therapy that contains the human LAMP2B transgene to help the synthesis of normal protein. Rocket hopes this will improve the condition.
This is the second clinical hold with this therapy, the first having been a ten-month hold on the Phase I trial of the therapy.
A fatality in Pfizer’s Phase II DMD gene therapy trial, as well as low efficacy in a Phase III study, caused the big pharma to drop the development of the AAV candidate, named fordadistrogene movaparvovec.
On 6 May, the FDA announced that American haematologist oncologist Vinay Prasad will lead its Center for Biologics Evaluation and Research (CBER), the division responsible for regulating gene therapies and vaccines.
Prasad has openly criticised Elevidys, primarily about the clinical evidence and the FDA’s decision to approve the therapy, which raises questions about his overall opinion of the gene therapy approach.
Rocket said that the patient received a dose of RP-A501 in the Phase II study (NCT06092034) and experienced clinical complications related to capillary leak syndrome. The patient later died after suffering an acute systemic infection.
Rocket Pharmaceutical CEO Dr Gaurav Shah said: “We are heartbroken by this loss and are fully committed to our mission to develop gene therapies that address the underlying cause of devastating diseases like Danon. We are immensely grateful for the patients and families who participate in this important research.”
Following the 27 May announcement, Rocket Pharmaceuticals’ stock, listed on the Nasdaq exchange, opened 63.32% lower than its close on 23 May.
William Blair healthcare analyst, Dr. Sami Corwin, said this drop is likely due to investors being hesitant about the programme’s safety and time to clinical hold resolution.
The US Food and Drug Administration (FDA) placed a clinical hold on the trial on 23 May, by which point Rocket had already paused dosing in the study. The pharmaceutical company is investigating the root cause of the AE and speaking with both the FDA and other key stakeholders.
Rocket said its current focus is the recent introduction of a novel immune suppression agent, a C3 inhibitor, to the pre-treatment regimen that had been implemented to mitigate complement activation seen in certain patients. This agent is specific to the Danon programme.
Corwin said: “The C3 inhibitor was administered pre- and post-RP-A501 treatment in combination with the enhanced prophylactic immunosuppressive regimen of sirolimus, rituximab, and prednisone. In addition, one other patient also received the modified immunosuppression regimen including the C3 inhibitor and also exhibited early signs of capillary leak syndrome but had a reduced course, further supporting the hypothesis that the compound played a role in the development of capillary leak syndrome.”
Rocket is also working with the FDA, the Independent Data Safety Monitoring Committee (IDSM), clinical investigators, and scientific experts to ensure the safety of all study patients, with hopes to resume the study when possible.
Danon disease is a rare, X-linked disorder caused by mutations in the lysosome-associated membrane protein 2 isoform B (LAMP2 gene). Symptoms include hypertrophic cardiomyopathy, skeletal muscle weakness, and intellectual disability.
RP-A501 is an adeno-associated virus serotype 9 (AAV9) gene therapy that contains the human LAMP2B transgene to help the synthesis of normal protein. Rocket hopes this will improve the condition.
This is the second clinical hold with this therapy, the first having been a ten-month hold on the Phase I trial of the therapy.
Other gene therapy fatalities
Rocket Pharmaceuticals is not the only company to have reported a fatality after administering an AAV gene therapy. In March 2025, Sarepta and Roche announced the death of a teenage patient dosed with its AAV gene therapy for Duchenne muscular dystrophy (DMD), Elevidys (delandistrogene moxeparvovec-rokl), causing agencies to pause ongoing clinical studies. This pause has since been lifted.A fatality in Pfizer’s Phase II DMD gene therapy trial, as well as low efficacy in a Phase III study, caused the big pharma to drop the development of the AAV candidate, named fordadistrogene movaparvovec.
On 6 May, the FDA announced that American haematologist oncologist Vinay Prasad will lead its Center for Biologics Evaluation and Research (CBER), the division responsible for regulating gene therapies and vaccines.
Prasad has openly criticised Elevidys, primarily about the clinical evidence and the FDA’s decision to approve the therapy, which raises questions about his overall opinion of the gene therapy approach.
Source: https://www.clinicaltrialsarena.com/news/patient-dies-rocket-danon-disease-gene-therapy-trial/
%20in%20a%20visually%20appealing%20way,%20without%20any%20text.%20The%20background%20is%20split_%20one%20side%20has%20a%20sci.webp)
.png)
Comments
Post a Comment