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

Dosage forms and strengths

15 evidence topics · 15 sources

Vector and transgene: AAV9 capsid containing the human LAMP2B transgene

“RP-A501 is a gene therapy product consisting of an rAAV9 capsid containing the human LAMP2B transgene which will be administered as a single IV infusion.” (opens the source at this quote in a new tab)

“RP-A501 consists of a recombinant adeno-associated serotype 9 (AAV9) capsid containing a full-length, wild-type version of the human LAMP2B transgene (AAV9.LAMP2B)” (opens the source at this quote in a new tab)

“RP-A501 represents a single dose treatment and is administered as an intravenous (IV) infusion.” (opens the source at this quote in a new tab)

“All Rocket therapies transfer full (non-truncated) coding sequence to target tissue” (opens the source at this quote in a new tab)

Expression cassette of the AAV9.LAMP2B vector in the preclinical mouse study: CAG promoter, WPRE, and AAV2 inverted terminal repeats

“To investigate the potential of gene therapy for the treatment of DD, we created an AAV9 vector overexpressing human LAMP2B (AAV9.LAMP2B) in collaboration with the University of Pennsylvania viral vector core.” (opens the source at this quote in a new tab)

“Transgene expression is under the control of the constitutively active CAG promoter” (opens the source at this quote in a new tab)

“This constitutively active promoter was chosen to allow for LAMP2B isoform expression in multiple tissues because DD is a multiorgan disorder” (opens the source at this quote in a new tab)

“The AAV cis-transfer plasmid pAAV-LAMP2B contains the transgene expression cassette flanked by viral ITR regions derived from AAV2.” (opens the source at this quote in a new tab)

“The expression cassette also includes the woodchuck hepatitis posttranscriptional regulatory element (WPRE)” (opens the source at this quote in a new tab)

Promoter and expression cassette of the clinical product RP-A501

No evidence found.

Pharmaceutical form and route of administration
FieldQuoted record
Pharmaceutical form“Solution for infusion”
Route of administration“Intravenous use”
Dose unit and doses in the phase 2 trial: genome copies per kilogram

“Dose of RP-A501: Cohorts 1, 2 & 3 = 6.7 x10^13 genome copies (GC)/kg; Cohort 4 = 3.8 x10^13 GC/kg.” (opens the source at this quote in a new tab)

Doses in the phase 1 trial
CohortQuoted record
Cohort 1“Cohort 1: Adult and age 15-17: 6.7 × 1013 GC/kg (n=3-4)”
Cohort 2“Cohort 2: Adult and age 15-17: 1.1 × 1014 GC/kg (n=2 [patients already treated; closed for current enrollment])”
Cohort 1A“Cohort 1A: Pediatric age 8-14: 6.7 × 1013 GC/kg (n=2-4)”
Dose unit as written in other company documents: gc/kg and vg/kg

“This includes a first cohort evaluating a low-dose (6.7e13 genome copies/kilogram ([gc/kg]; n=3) in adult/older adolescent patients aged 15 or greater, a second cohort evaluating a higher dose (1.1e14 gc/kg; n=2) in adult/older adolescent patients aged 15 or greater, and a pediatric cohort at a low dose level (6.7e13 gc/kg; n=2).” (opens the source at this quote in a new tab)

“We continue to anticipate reporting updated longer-term data from the low-dose (6.7e13 vg/kg) and higher-dose (1.1e14 vg/kg) young adult cohorts in the fourth quarter.” (opens the source at this quote in a new tab)

Recalibrated dose of 3.8 × 10¹³ GC/kg: relation to the full capsid content of the current drug product

“This recalibration accounts for the higher proportion of full capsids in the current drug product in the setting of Danon disease and was developed in consultation with leading experts and the FDA.” (opens the source at this quote in a new tab)

“The recalibrated dose was selected based on analytical characterization of the Phase 2 commercial-grade product, including its full-particle content, and is supported by nonclinical bridging data.” (opens the source at this quote in a new tab)

“Dose recalibrated to account for the higher full-to-empty capsid ratio” (opens the source at this quote in a new tab)

“The recalibrated Phase 2 dose of 3.8 × 10¹³ GC/kg was selected based on the characteristics of the current drug product, the underlying biology of Danon disease and the Phase 1 experience, with the objective of preserving the potential for meaningful clinical benefit while optimizing RP-A501’s benefit-risk profile.” (opens the source at this quote in a new tab)

Recalibrated dose: rationale stated when the 2025 hold was lifted

“This adjusted dose aligns with the lower range of administered doses that were associated with efficacy across multiple biomarkers, echocardiographic and clinical endpoints in the Phase 1 study, and has been determined as most likely to confer the safety and efficacy identified in the low-dose Phase 1 cohorts.” (opens the source at this quote in a new tab)

Numerical full-to-empty capsid ratio of the phase 1 and phase 2 drug product

No evidence found.

Nonclinical bridging of phase 2 material at the recalibrated dose

“In a Danon disease mouse model, administration of Phase 2 material at 3.8 × 10¹³ GC/kg resulted in cardiac LAMP2B protein expression comparable to that observed at a higher dose and demonstrated comparable vector biodistribution.” (opens the source at this quote in a new tab)

Manufacturing site and process: in-house production at Cranbury, New Jersey, with a HEK-293 cell-based process

“Drug product for the Phase 2 study is being produced in-house in our GMP manufacturing facility in Cranbury, NJ.” (opens the source at this quote in a new tab)

“We have successfully produced multiple commercial-grade Danon AAV cGMP batches since 2022.” (opens the source at this quote in a new tab)

“Furthermore, we have reached agreement with the FDA on the continued utilization of HEK-293 cell-based process through commercialization, our comparability approach and our potency assay.” (opens the source at this quote in a new tab)

“We commenced GMP manufacturing at our facility in Cranbury, New Jersey in 2022.” (opens the source at this quote in a new tab)

Manufacturing facility size

“Rocket’s corporate headquarters is located in Cranbury, New Jersey, in a leased facility consisting of 103,720 square feet of space including areas for offices, process development, research and development laboratories and 50,000 square feet dedicated to AAV cGMP manufacturing to support our pipeline.” (opens the source at this quote in a new tab)

In-house batches compared with phase 1 material (January 2023)

“2 Successful Danon AAV cGMP batches produced in Q4 2022” (opens the source at this quote in a new tab)

“Superior specifications to Phase I material; allow for full dosing with lower total viral particles, potentially further improving safety profile” (opens the source at this quote in a new tab)

“Productivity: ~3X increase in number of patient treatments per batch” (opens the source at this quote in a new tab)

“Product Quality: Significant increase in full versus empty viral particles” (opens the source at this quote in a new tab)

“Product Comparability: All attributes tested to date are comparable or improved” (opens the source at this quote in a new tab)

FDA positions on the manufacturing process reported in January 2023

“FDA clearance on continued utilization of HEK-293 cell-based process through commercial” (opens the source at this quote in a new tab)

“FDA alignment on comparability approach” (opens the source at this quote in a new tab)

“Potency assay developed in-house” (opens the source at this quote in a new tab)

Drug product supply for the pivotal trial (September 2023)

“In-house manufacturing has been completed with sufficient high-quality drug product produced to fully supply the Phase 2 pivotal study.” (opens the source at this quote in a new tab)

“Potency assays have been developed and qualified in accordance with FDA guidance.” (opens the source at this quote in a new tab)

“Dose: 6.7 x 1013 GC/kg of commercially representative RP-A501 material” (opens the source at this quote in a new tab)

“Multiple GMP lots manufactured in-house; sufficient drug product produced for full pivotal trial” (opens the source at this quote in a new tab)

“Successful QP audit of Rocket manufacturing facility; drug product cleared for EU use” (opens the source at this quote in a new tab)

Production of the vector used in the preclinical mouse study

“Recombinant AAV9 vector expressing human LAMP2B was generated through a three-plasmid, helper virus–free system in collaboration with the viral vector core at the University of Pennsylvania.” (opens the source at this quote in a new tab)

Commercial presentation, concentration, fill volume, storage, and packaging

No evidence found.