Evicenter
P&T meetings

RP-A501 (AAV9.LAMP2B)

Danon disease

Regulatory submission
BLA planned for late 2028
Last updated
300 sources

Product information and disease descriptionProduct descriptionProduct informationDrug/Drug, drug/disease interactions

Effects of other drugs on RP-A501

8 evidence topics · 11 sources

Formal drug interaction studies of RP-A501

No evidence found.

Interaction between a C3 complement inhibitor and RP-A501 identified in the regulatory review

“In August 2025, the FDA lifted the clinical hold on the Phase 2 pivotal study following an investigation which concluded that the SAEs were likely the result of the combination of the C3 component inhibitor introduced into the immunomodulation regimen and RP-A501.” (opens the source at this quote in a new tab)

“The safety review concluded that the severe adverse events were likely the result of the combination of the complement C3 inhibitor introduced into the immunomodulation regimen and the investigational product.” (opens the source at this quote in a new tab)

“Rocket is conducting a comprehensive root cause analysis and remains in active dialogue with the U.S. Food and Drug Administration (FDA) and other key stakeholders, with the current focus being on the recent introduction of a novel immune suppression agent to the pre-treatment regimen that had been implemented to mitigate complement activation observed in some patients. This novel agent was specific to the AAV9-Danon program.” (opens the source at this quote in a new tab)

Proposed mechanism of the interaction between C3 inhibition and the vector

“A potential mechanism has subsequently been proposed, whereby complement inhibition with the C3 inhibitor may have reduced AAV opsonization and increased vector uptake by endothelial cells, leading to vascular endothelial injury[13].” (opens the source at this quote in a new tab)

“In that study, patients had received prophylactic treatment with pegacetoplan, an FDA-approved complement inhibitor, and investigators suspect that pegacetoplan facilitated binding of a low concentration complement complexes to endothelial cells to cause diffuse capillary leak, which manifested as pulmonary edema and hemoconcentration.” (opens the source at this quote in a new tab)

Identity of the C3 inhibitor in the registry record for the phase 2 trial

“Cohort 3: Males age ≥ 8 years receiving a pegcetacoplan-containing immunomodulatory regimen [N=2 subjects; enrollment closed]” (opens the source at this quote in a new tab)

“Pegcetacoplan was incorporated into the immunomodulation regimen for Cohort 3 but excluded in Cohort 4.” (opens the source at this quote in a new tab)

Effect of prophylactic immunomodulation on the antibody and complement response to the vector

“This study demonstrates that TMA in the setting of AAV gene therapy is antibody dependent (classical pathway) and amplified by the alternative complement pathway.” (opens the source at this quote in a new tab)

“Group 2 patients did not have a significant change in IgM or IgG and had minimal complement activation.” (opens the source at this quote in a new tab)

“Importantly, we have identified an approach for pretreatment using rituximab and sirolimus that protects from an early IgM and IgG response that is the key trigger to safety events in the first week following systemic gene therapy.” (opens the source at this quote in a new tab)

“In a study by Byrne et al. of SMA, DMD, GM1, and Danon disease patients receiving investigational or FDA-approved AAV9 gene therapies, prophylactic treatment with rituximab and sirolimus in addition to corticosteroids prevented anti-AAV antibody formation to a greater extent than corticosteroids alone [ 82 ].” (opens the source at this quote in a new tab)

Effect of corticosteroid compliance on myocardial transgene expression

“The first patient in the low dose cohort was not as closely monitored for compliance with the immunosuppressive regimen as the other two patients.” (opens the source at this quote in a new tab)

“These changes were largely responsive to corticosteroids and other immunosuppressive therapies.” (opens the source at this quote in a new tab)

“1 Does not include patient 1001 (unmonitored immunomodulation).” (opens the source at this quote in a new tab)

Prior exposure to adeno-associated virus vectors

“Please note: this study is not available to those currently participating in any other investigational clinical studies or who have received any other gene therapy treatment” (opens the source at this quote in a new tab)

Contraindication to sirolimus as an exclusion criterion

“Any contraindication to use of sirolimus which includes hypersensitivity to sirolimus or HC-60 (polyoxyl 60 hydrogenated castor oil).” (opens the source at this quote in a new tab)

Vaccination required before administration

“Patient has received meningococcal vaccination recommended by Centers for Disease Control as appropriate for age and health condition (vaccination must be performed at least 6 weeks prior to IP administration).” (opens the source at this quote in a new tab)

“Has received approved vaccination against Neisseria meningitidis ≥ 6 weeks before administration of RP-A501.” (opens the source at this quote in a new tab)