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 information

Co-prescribed/Concomitant therapies

10 evidence topics · 15 sources

Immunomodulation regimen by cohort and dose, as of October 2026
Trial and cohortPopulation and number dosedDoseImmunomodulatory regimen
Phase 1, cohort 1“Adult/Adolescent (n=3)”“6.7 x 10¹³ GC/kg”“Steroid (n=1); Steroid + Tacrolimus (n=2)”
Phase 1, cohort 2“Adult/Adolescent (n=2)”“1.1 x 10¹⁴ GC/kg”“Rituximab + Steroid + Tacrolimus”
Phase 1, cohort 1A“Pediatric (n=2)”“6.7 x 10¹³ GC/kg”“Rituximab + Steroid + Sirolimus”
Phase 2, cohort 1“Adult/Adolescent (n=1)”“6.7 x 10¹³ GC/kg”“Rituximab + Steroid + Sirolimus”
Phase 2, cohort 2“Pediatric (n=3)”“6.7 x 10¹³ GC/kg”“Rituximab + Steroid + Sirolimus”
Phase 2, cohort 3“Adult/Adolescent and Pediatric with C3 inhibitor (n=2)”“6.7 x 10¹³ GC/kg”“Rituximab + Steroid + Sirolimus + C3 inhibitor”
Phase 2, cohort 4“Adult/Adolescent and Pediatric (n=12)”“3.8 x 10¹³ GC/kg”“Rituximab + Steroid + Sirolimus”

“Included initial sequential Pediatric Safety Run-in (n=2)” (opens the source at this quote in a new tab)

Phase 1 regimen as administered, by cohort

“RP-A501 Steroid (prednisone 1mg/kg) Tacrolimus Tacrolimus Rituximab (2 doses) Steroid (prednisone 0.5-0.8mg/kg): taper starting day 10 Sirolimus (target trough 4-8 ng/mL) Rituximab (2 doses) RP-A501 RP-A501 Cohort 1: Low-dose adult N=3 Cohort 2: High-dose adult” (opens the source at this quote in a new tab)

“Dose Discontinued” (opens the source at this quote in a new tab)

“N=2 Cohort 3: Low-dose pediatric N=2 Steroid (prednisone 1mg/kg) Day 14 D/C Month 3 Day -14” (opens the source at this quote in a new tab)

“Steroid (prednisone 0.5 – 0.8mg/kg and tapered starting day 10) Sirolimus (target trough 4-8 ng/mL) Rituximab (2 doses) RP-A501 Pediatric immunomodulation protocol” (opens the source at this quote in a new tab)

“All the patients received a transient immunomodulatory regimen of prednisone, tacrolimus or sirolimus, and rituximab.” (opens the source at this quote in a new tab)

Changes to the phase 1 regimen during the trial

“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)

“Currently-Implemented Protocol Risk Mitigation: • No further enrollment at HIGHER dose • Adjusted immunosuppressive regimen • Corticosteroids: Limit daily dose • Sirolimus: Minimize renal impact • Frequent monitoring for early signs of TMA • Rituximab continued” (opens the source at this quote in a new tab)

“Prior to infusion of IP, rituximab and sirolimus will be administered prophylactically.” (opens the source at this quote in a new tab)

Number of rituximab doses by phase 2 cohort

“The regimen includes rituximab or a biosimilar, administered in two doses for Cohorts 1-3 and three doses for Cohort 4, along with sirolimus and corticosteroids.” (opens the source at this quote in a new tab)

Revision of the phase 2 regimen after the May 2025 events

“In addition, Rocket will collaborate with investigators to implement an immunomodulatory regimen more closely reflecting that administered in the Phase 1 pediatric cohort. The revised regimen discontinues prophylactic use of a C3 complement inhibitor, while maintaining sirolimus, rituximab, and steroids.” (opens the source at this quote in a new tab)

“In parallel, the immunomodulatory regimen was restructured. Prophylactic administration of the C3 complement inhibitor was discontinued, while maintaining immunosuppression with sirolimus, rituximab, and corticosteroids.” (opens the source at this quote in a new tab)

Immunomodulatory and supportive medicines in the European Union application
AgentForm and routeMaximum daily doseMaximum duration
Rituximab“CONCENTRATE FOR SOLUTION FOR INFUSION Route of administration INTRAVENOUS INFUSION”“750 mg/m2 milligram(s)/square meter”“2 Week(s)”
Sirolimus“COATED TABLET Route of administration ORAL USE”“2 mg milligram(s)”“3 Month(s)”
Prednisone“TABLET Route of administration ORAL USE”“60 mg milligram(s)”“3 Month(s)”
Methylprednisolone sodium succinate“POWDER FOR SOLUTION FOR INFUSION Route of administration INTRAVENOUS USE”“0.8 mg/kg milligram(s)/kilogram”“4 Week(s)”
Eculizumab“SOLUTION FOR INFUSION Route of administration INTRAVENOUS INFUSION”“1200 mg milligram(s)”“3 Month(s)”
Paracetamol“TABLET Route of administration ORAL USE”“1 g gram(s)”“2 Week(s)”
Diphenhydramine hydrochloride“TABLET Route of administration ORAL USE”“50 mg milligram(s)”“2 Week(s)”
Duration of immunosuppression after administration

“These measures include exclusion of patients with end-stage HF, and a refined immunomodulatory regimen involving transient B- and T-cell mediated inhibition, with emphasis on preventing complement activation, while also enabling lower steroid doses and earlier steroid taper, with all immunosuppressive therapy discontinued 2-3 months following administration of RP-A501.” (opens the source at this quote in a new tab)

Class context: immunosuppressive regimen recorded for the Danon disease program in a systematic review

“Danon 23 1 1 0 0 AAV-9 6.7 × 10 13 to 1.1 × 10 14 vg/kg 0 0 1” (opens the source at this quote in a new tab)

“Notably, higher vector doses were associated with increased risk of immunotoxicity, whereas multimodal immunosuppression was associated with a lower risk[19].” (opens the source at this quote in a new tab)

Background cardiac therapy that participants continue

“Patients typically on maximal medical management (e.g. beta blockers, ICD) - none alter disease progression” (opens the source at this quote in a new tab)

“Standard of care: ICD placement, anti-arrhythmic & CHF medications – none markedly modify disease progression” (opens the source at this quote in a new tab)

“I.V. therapy with positive inotropes, vasodilators, or diuretics within the 30 days prior to enrollment (i.e., patient must be stable on oral medical therapy).” (opens the source at this quote in a new tab)

“You will continue to see your doctor for regular care.” (opens the source at this quote in a new tab)

Implantable cardioverter-defibrillator use among treated participants

“1 Recommended prior to enrollment; ICD implanted 3 months after RP-A501” (opens the source at this quote in a new tab)