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 descriptionPlace of product in therapyApproaches to treatment

Care management intervention strategies

21 evidence topics · 18 sources

Eligibility assessment: baseline testing at the study site

“This will occur at the study site and includes ECHO, EKG, cardiac MRI, heart biopsy” (opens the source at this quote in a new tab)

Eligibility assessment: anti-AAV9 antibody testing

“Anti-AAV9 neutralizing antibody titer >1:40.” (opens the source at this quote in a new tab)

Eligibility assessment: three-month biomarker run-in before treatment, as stated in August 2025

“All patients enrolled in the trial are required to have a three-months observational pre-treatment run-in to enable an assessment of troponin (and other biomarker) trajectories to optimally assess this key secondary endpoint.” (opens the source at this quote in a new tab)

Immunomodulation: regimen under the modified protocol

“The modified protocol incorporates a recalibrated RP-A501 dose and an optimized immunomodulatory regimen comprised of rituximab, sirolimus and corticosteroids, together with enhanced eligibility criteria, safety monitoring and risk-mitigation measures.” (opens the source at this quote in a new tab)

Immunomodulation: changes made during phase 1 to limit steroid myopathy and renal toxicity

“During the study, the immunomodulatory regimen was progressively adapted: steroid doses were reduced to mitigate steroid-induced myopathy, tacrolimus was replaced with sirolimus to reduce the risk of renal toxicity, and rituximab was introduced.” (opens the source at this quote in a new tab)

Immunomodulation: infection during treatment

“In May 2025, two patients developed severe adverse events characterized by capillary leak syndrome leading to multi-organ dysfunction, with one fatal outcome following an intercurrent systemic infection.” (opens the source at this quote in a new tab)

Infection prophylaxis regimen during immunomodulation

No evidence found.

Complement monitoring and threshold for a C5 inhibitor

“Additionally, the protocol will specify a lower threshold for administering a C5 inhibitor (eculizumab) in response to impending complement activation.” (opens the source at this quote in a new tab)

“Given the recognized association between systemic AAV administration, complement activation, and thrombotic microangiopathy, a more reactive strategy was adopted for complement-mediated complications” (opens the source at this quote in a new tab)

Platelet and terminal complement complex monitoring for 3 months in the first 3 participants at the recalibrated dose

“Platelets and Terminal Complement Complex (sC5b9) of the initial 3 patients up to 3 months post-treatment” (opens the source at this quote in a new tab)

“A decrease in platelet count was observed at Week 8-9 in the absence of symptoms or signs suggestive of platelet dysfunction or deficit.” (opens the source at this quote in a new tab)

“No evidence of thrombotic microangiopathy, capillary leak or other complement-mediated events” (opens the source at this quote in a new tab)

Timing of immune adverse events after AAV gene therapy: meta-analysis across diseases

“Time course analyses revealed TMA clustered in week 1, myocarditis at week 2, and hepatotoxicity up to 6 months post-infusion.” (opens the source at this quote in a new tab)

Sequential dosing interval

“Treatment proceeded sequentially, with a minimum of four weeks between infusions.” (opens the source at this quote in a new tab)

Cardiac and extracardiac surveillance schedule in the consensus statement
TestFrequency during follow-up care
Blood tests“Yearly”
24-hour Holter monitoring“Every 6 mo if enlarged atria”
Cardiac magnetic resonance“Every 2-3 y”
Neurologic evaluation“Yearly if symptoms, otherwise, every 3-4 y”
Development evaluation“At baseline and if new manifestations appear”
Ophthalmologic evaluation“Every 3-5 y”
Genetic counseling“At diagnosis and when needed”

“There are no guidelines specific to Danon disease to guide the frequency of follow-up care, but given the potential for rapid disease progression and the high risk of ventricular arrhythmia and heart failure complications, it is reasonable to recommend clinical cardiologic follow-up with 12-lead ECG, echocardiogram, and ambulatory Holter monitoring at least annually.” (opens the source at this quote in a new tab)

“We recommend that CMR imaging be repeated every 2 to 3 years to monitor progression of fibrosis.” (opens the source at this quote in a new tab)

Surveillance schedule in GeneReviews
EvaluationFrequency
Electrocardiography“At least annually”
Echocardiography“At least every 1-2 yrs, transitioning to every 6 mos once hypertrophy becomes moderate or if hypertrophy is rapidly progressive”
Cardiac MRI“Consider every 1-2 yrs to evaluate progression of fibrosis.”
Ambulatory arrhythmia monitoring“As needed for eval of symptoms consistent w/bypass track (e.g. palpitations, pre-syncope)”
Formal developmental assessments“Every 3-5 yrs during childhood”
Ophthalmologic examination“Every 3-5 yrs or as needed based on concerns about visual acuity, visual field deficits, &/or color vision (as an indicator of cone function)”
Surveillance of genotype-positive relatives without cardiomyopathy

“Consequently, although both sexes should be screened during infancy (first year of life), yearly multidisciplinary follow-up care is recommended to begin at that time in boys, whereas girls can start annual follow-up visits around the age of 6 years.” (opens the source at this quote in a new tab)

Family cascade testing

“First, cascade genetic screening of relatives should be recommended at the time of diagnosis; second, family planning strategies should be introduced when a patient reaches reproductive age.” (opens the source at this quote in a new tab)

“It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from prompt initiation of treatment and preventive measures.” (opens the source at this quote in a new tab)

Company-sponsored genetic testing program: eligibility and family variant testing

“This program is available to patients 40 years of age or younger, in the United States, with a high suspicion of an inherited cardiomyopathy.” (opens the source at this quote in a new tab)

“All blood relatives of patients tested through this sponsored testing program and found to have a pathogenic or likely pathogenic variant are eligible” (opens the source at this quote in a new tab)

Transition planning and educational support

“As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP.” (opens the source at this quote in a new tab)

“Assess family need for social work support (e.g., respite care, home nursing, other local resources) & care coordination.” (opens the source at this quote in a new tab)

Patient and caregiver experience of gene therapy administration

“Evaluating the experiences of patients and their caregivers, through patient-reported outcomes and qualitative interviews, could help identify areas for intervention to reduce treatment burden and improve overall care.” (opens the source at this quote in a new tab)

Long-term follow-up in the RP-A501 studies

“The trial will include a total of 5 years of follow-up after administration of RP-A501.” (opens the source at this quote in a new tab)

“After the end of the follow-up period, patients will enter a Long-Term Follow-Up (LTFU) study enabling follow-up for an additional 2 to 5 years post-IP administration.” (opens the source at this quote in a new tab)

“Phase 1 LTFU: up to 10 years (ongoing)” (opens the source at this quote in a new tab)

FDA guidance: duration of long-term follow-up by product type

“Up to five years for AAV vectors.” (opens the source at this quote in a new tab)

“Additionally, a risk-based approach for determining the duration of a LTFU protocol may be considered for vectors capable of latency (e.g., Herpesvirus), long term expression without integration (e.g., AAV), or vectors carrying gene editing components.” (opens the source at this quote in a new tab)

“FDA guidance advises that patients treated with some types of gene therapy undergo follow-up observations for potential adverse events for as long as 15 years.” (opens the source at this quote in a new tab)

FDA guidance: yearly examinations and registries after gene therapy

“We recommend that LTFU observations include scheduled physical examinations performed by a HCP once a year during the first five years (or until the completion of LTFU if the LTFU is less than five years), unless the assessed risks associated with your GT product indicate that they should be done more frequently.” (opens the source at this quote in a new tab)

“For instance, we may recommend that you establish a registry, or use an existing patient registry, to systematically capture and track data from treated patients with solicited sample collection (if applicable), and follow-up of adverse events to resolution or stabilization to collect additional pertinent data.” (opens the source at this quote in a new tab)

Natural history study and registry

“A subset of patients will be used as an External Control Arm for comparison to RP-A501 Trial participants.” (opens the source at this quote in a new tab)

“Data were from the International Danon Disease Registry that includes patients from the United States and Europe who gave consent to be part of the study between 2005 and 2022.” (opens the source at this quote in a new tab)