Evicenter
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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

Heterogeneity of treatment effect

14 evidence topics · 9 sources

Evidence base: individual-level description without statistical testing

“Since this was a single-arm study, safety and efficacy outcomes were described using observed values and absolute or relative changes from baseline at the individual-patient level.” (opens the source at this quote in a new tab)

“No formal statistical hypothesis testing was performed.” (opens the source at this quote in a new tab)

“The small sample sizes and early-phase design preclude definitive conclusions regarding clinical efficacy or long-term safety.” (opens the source at this quote in a new tab)

Sex: all treated participants are male

“RP-A501 infusion was administered to seven male patients with Danon disease: five who were 15 years of age or older and two who were between 11 and 14 years of age.” (opens the source at this quote in a new tab)

“RP-A501-0123 is a Phase 2 global, multi-center, single arm, open-label, single dose trial in males with Danon disease.” (opens the source at this quote in a new tab)

Sex: barriers to a trial in females

“Nonetheless, without clarity regarding the natural history of the disease, it may be challenging to identify appropriate surrogates of mortality or design a trial in female individuals.” (opens the source at this quote in a new tab)

“This may be due to a possible bimodal distribution in age at which female patients experience a HF outcome” (opens the source at this quote in a new tab)

Baseline ejection fraction: single phase 1 participant with systolic dysfunction who progressed to transplantation

“One patient with left ventricular systolic dysfunction at baseline had progressive heart failure and underwent transplantation 5 months after infusion.” (opens the source at this quote in a new tab)

“In the six patients with normal left ventricular ejection fraction at baseline, we observed cardiac LAMP2 protein expression and a reduction from baseline in or stabilization of the left ventricular mass index, preservation of left ventricular ejection fraction, and reduction in or stabilization of the levels of cardiac troponin I and N-terminal pro-B-type natriuretic peptide.” (opens the source at this quote in a new tab)

“This patient had more advanced disease than the four other adult/older adolescent patients who received treatment in the low and high dose cohorts, as evidenced by diminished baseline left ventricle ejection fraction (32%) on echocardiogram and markedly elevated left ventricle filling pressure prior to treatment.” (opens the source at this quote in a new tab)

“The patient’s clinical course was characteristic of DD progression.” (opens the source at this quote in a new tab)

Later transplantation in a pediatric low-dose participant: single observation after the July 2026 data cut

“Patient underwent heart transplant at 4.8 years post-RP-A501 infusion; post data cut.” (opens the source at this quote in a new tab)

Age and dose cohort: left ventricular mass index change by phase 1 participant at the most recent visit (36 to 84 months), data extracted July 31, 2026
CohortParticipantChange in left ventricular mass index, baseline to most recent visit (g/m2.7)
Low dose, adult or adolescent1“-32%, 85.0 to 57.8”
Low dose, adult or adolescent2“-31%, 260.2 to 178.9”
Low dose, adult or adolescent3“-12%, 98.2 to 86.7”
High dose, adult or adolescent4“-7%, 68.6 to 63.6”
Low dose, pediatric6“-47%, 141.5 to 74.7”
Low dose, pediatric7“+3%, 82.0 to 84.9”
Original-dose phase 2 cohorts: response in 3 of 4 participants

“Three of four patients with longitudinal efficacy assessments achieved at least a 10% reduction in left ventricular mass index.” (opens the source at this quote in a new tab)

Dose level: high dose discontinued after thrombotic microangiopathy in 1 of 2 participants

“The high dose was discontinued after one of the two patients treated at this dose developed thrombotic microangiopathy” (opens the source at this quote in a new tab)

Dose level: outcomes at the recalibrated dose not yet known

“Preliminary findings may change as additional data become available, and results from earlier cohorts may not predict outcomes at the recalibrated dose under the modified protocol.” (opens the source at this quote in a new tab)

“Although data remain preliminary, this cohort represents an important opportunity to evaluate whether dose reduction and modified immune modulation can preserve efficacy while reducing toxicity.” (opens the source at this quote in a new tab)

Immunomodulatory regimen: serious adverse events in both participants given a C3 inhibitor

“In Phase 2 Cohort 3, two patients treated with immunomodulatory regimen containing a C3-inhibitor experienced serious adverse events.” (opens the source at this quote in a new tab)

Skeletal myopathy: corticosteroid-related exacerbation in 3 of 7 phase 1 participants

“Three patients had glucocorticoid-related exacerbation (grade 3) of Danon disease-related skeletal myopathy.” (opens the source at this quote in a new tab)

Anti-AAV9 antibody status: participants with pre-existing antibodies not treated

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

“Furthermore, additional challenges with gene therapy include efficiency issues due to pre-existing antibodies or robust immune responses that require immunosuppressive therapy, inability to re-treat patients if therapy fails over time, and safety concerns about potential off-target effects.” (opens the source at this quote in a new tab)

Genotype: variant class and phenotype severity

“Over 160 separate LAMP2 variants cause Danon Disease and genotype-phenotype correlation is yet to be clarified.” (opens the source at this quote in a new tab)

“However, exonic variants are usually associated with the absence of LAMP-2b, while intronic variants may still retain the ability to produce functional protein and be associated with milder phenotypes” (opens the source at this quote in a new tab)

“There was no significant difference when comparing nonsense to frameshift and splice-site mutations for age of diagnosis, age of death or heart transplant (Suppl.Tab 2).” (opens the source at this quote in a new tab)

Treatment response by LAMP2 variant type

No evidence found.

Organ system: extracardiac manifestations

“Whereas gene therapy may ameliorate cardiac symptoms, extracardiac symptoms including skeletal myopathy, retinal impairment, and intellectual disability will be largely unaffected by this therapy.” (opens the source at this quote in a new tab)