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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 descriptionProduct descriptionProduct information

Product comparison

18 evidence topics · 21 sources

Adeno-associated virus serotype 2i8 vector carrying the human LAMP2 isoform B transgene: European orphan designation, May 2025
FieldQuoted record
Active substance“adeno-associated viral vector serotype 2i8 containing the human LAMP2 isoform B transgene”
Intended use“Treatment of Danon disease”
Orphan designation status“Positive”
EU designation number“EU/3/25/3062”
Date of designation“22/05/2025”
Sponsor“AskBio France”

“Orphan designation does not mean the medicine is available or authorised for use.” (opens the source at this quote in a new tab)

“All medicines, including designated orphan medicines, must be authorised before they can be marketed and made available to patients in the EU.” (opens the source at this quote in a new tab)

PPL-002 (Papillon Therapeutics): gene-modified hematopoietic stem and progenitor cells, FDA orphan drug designation announced October 2024

“Papillon Therapeutics Inc., a clinical-stage biotechnology company advancing a pipeline of multi-systemic genetic medicines directed at the underlying causes of inherited disease, today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to Papillon’s PPL-002, an experimental treatment for Danon disease.” (opens the source at this quote in a new tab)

“PPL-002 is an experimental gene-modified CD34+ hematopoietic stem and progenitor cell (HSPC) therapy for the treatment of Danon disease.” (opens the source at this quote in a new tab)

“This therapeutic is designed to express functional Lamp-2 protein, which is critically deficient in people living with Danon disease.” (opens the source at this quote in a new tab)

“In preclinical studies, PPL-002 has been shown to improve disease phenotype in the affected tissues.” (opens the source at this quote in a new tab)

“PPL-002 research is funded in part by the California Institute for Regenerative Medicine (CIRM).” (opens the source at this quote in a new tab)

Hematopoietic stem cell approach: grant objective, candidate, and proposed mechanism
FieldQuoted record
Grant number“TRAN1-15230”
Institution“University of California, San Diego”
Award value“$5,180,389”
Translational candidate“The candidate is CD34+ HSPCs transduced ex vivo with a LAMP2 lentiviral vector.”
Project objective“Submission of Pre-IND materials”

“Engrafted HSPC progeny will supply normal LAMP2B to the heart, liver, muscle, and brain via lysosomal cross-correction.” (opens the source at this quote in a new tab)

“Pilot pharmacology studies of PA_001 surrogate to ameliorate DD in a mouse model of the disease.” (opens the source at this quote in a new tab)

Hematopoietic stem cell approach: results in a mouse model presented in November 2025

“Aims: We evaluated whether ex vivo gene-modified hematopoietic stem and progenitor cells (HSPCs) could deliver LAMP2B to affected tissues and improve outcomes in a murine model of Danon disease.” (opens the source at this quote in a new tab)

“Methods: Sca-1 positive HSPCs were isolated from Lamp2 KO mice and transduced with pALD-LAMP2B (n=5) or left unmodified (n=6).” (opens the source at this quote in a new tab)

“Cells were transplanted into busulfan-conditioned 12–15-week-old Lamp2 KO recipients.” (opens the source at this quote in a new tab)

“These mice exhibited improved cardiac function compared to those receiving unmodified KO HSPCs (End diastolic pressure: p=0.005; Tau: p=0.06; Max dP/dt: p=0.28; Min dP/dt: p=0.30).” (opens the source at this quote in a new tab)

“Conclusions: Transplantation of gene-modified HSPCs restored LAMP2B expression in the heart and improved both cardiac and neurobehavioral outcomes in a Danon disease mouse model.” (opens the source at this quote in a new tab)

Lipid nanoparticle LAMP2 messenger RNA: results in patient-derived cardiomyocytes presented in 2025

“We used patient-derived Danon iPSC-Cardiomyocytes (iPSC-CMs) and delivered lipid nanoparticle (LNP)-encapsulated LAMP2 mRNA to restore LAMP2 protein expression and lysosomal function, leading to phenotypic recovery.” (opens the source at this quote in a new tab)

“LAMP2 protein expression was confirmed in iPSC-CMs via Western blot and immunocytochemistry.” (opens the source at this quote in a new tab)

“Conclusion: Our study demonstrates that LNP-mRNA therapy restores LAMP2 protein levels in cardiac cells, presenting a novel therapeutic strategy for Danon disease.” (opens the source at this quote in a new tab)

Company statement on gene therapy competitors, February 2026

“Although we are not currently aware of any gene therapy competitors addressing any of the same indications as those in our pipeline, we may have competitors both in the U.S. and internationally, including major multinational pharmaceutical companies, biotechnology companies and universities and other research institutions.” (opens the source at this quote in a new tab)

“Competitors, however, may receive approval of different products for the same orphan indication, or the same product for a different indication, during the exclusivity period.” (opens the source at this quote in a new tab)

Third-party descriptions of the development stage of RP-A501 relative to other approaches

“As RP-A501 is the only drug that is currently being developed in this indication, GlobalData analysts estimate that it will make $364m in sales by 2031 if approved.” (opens the source at this quote in a new tab)

“It is also the disorder in which disease-modifying therapy is most advanced, with AAV-mediated LAMP2B delivery currently undergoing clinical evaluation” (opens the source at this quote in a new tab)

Registered interventional trial of a product other than RP-A501 for Danon disease

No evidence found.

Heart transplantation as the current definitive treatment: company statements

“The only available definitive treatment option for Danon disease is cardiac transplantation, which is associated with substantial complications and is not considered curative, representing the high unmet medical need for patients with Danon disease.” (opens the source at this quote in a new tab)

“There are no specific therapies available for the treatment of DD and medications typically utilized for the treatment of HF are not believed to modify progression to end-stage HF.” (opens the source at this quote in a new tab)

“Patients with end-stage HF may undergo heart transplant, which currently is available to a minority of patients, is associated with significant short- and long-term complications and is not curative of the disorder in the long-term.” (opens the source at this quote in a new tab)

Heart transplantation: company presentation of access and outcomes, October 2026

“Heart transplantation is the only end-stage rescue and only for a few” (opens the source at this quote in a new tab)

“Only ~25% ultimately receive heart transplant (HTx)” (opens the source at this quote in a new tab)

“87.1% 5-year graft survival in Danon HTx cohort” (opens the source at this quote in a new tab)

“5 of 8 Died within 1 year after HTx/LVAD in a Danon cohort” (opens the source at this quote in a new tab)

Heart transplantation in Danon disease: graft survival in 38 recipients from 8 centers

“METHODS: The clinical phenotype and outcome data of patients with DD who underwent cardiac transplantation (n = 38; 19 males and 19 females) were obtained from 8 centers.” (opens the source at this quote in a new tab)

“RESULTS: Median follow-up time after transplantation for the entire cohort was 4.4 years (IQR: 1.5-12.8 years).” (opens the source at this quote in a new tab)

“There were 2 deaths in the entire cohort and 2 retransplants.” (opens the source at this quote in a new tab)

“There was no difference in actuarial graft survival between males and females (P = 0.8965); the estimated graft survival was 87.1% (95%CI: 63.6%-95.9%) at 5 years.” (opens the source at this quote in a new tab)

“One episode (2.7%) of antibody-mediated rejection, grade 2, and 7 episodes (19%) of acute cellular rejection, grade 2 or 3, were reported in patients who survived to discharge (6 females and 1 male; P = 0.172).” (opens the source at this quote in a new tab)

Heart transplantation and gene therapy in the international consensus statement

“Cardiac transplantation may be required for those in whom end-stage cardiomyopathy develops.” (opens the source at this quote in a new tab)

“Despite the presence of extracardiac involvement including skeletal muscle disease, which may limit rehabilitation, post-transplantation outcomes are good.” (opens the source at this quote in a new tab)

“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)

“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)

RP-A501 phase 1: survival and heart transplantation after infusion

“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)

“At 24 to 54 months, all the patients were alive, with complete resolution of side effects.” (opens the source at this quote in a new tab)

“100% overall survival; median transplant-free survival not reached at median follow-up: 5.7 years (range: 4.3–7.1 years)” (opens the source at this quote in a new tab)

“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)

“Data Extraction Date: July 31, 2026” (opens the source at this quote in a new tab)

Barriers to a controlled comparison of treatments in Danon disease

“Clinical Trial Design Additionally, although cardiac transplantation remains the only therapeutic option with a survival benefit, a Phase I gene therapy trial in DD has been completed and a Phase II AAV9 gene therapy trial is pending enrollment.” (opens the source at this quote in a new tab)

“Major barriers to designing a DD comparative effectiveness trial with a traditional control population include low disease prevalence, incidence of outcomes, and treatment effect sizes.” (opens the source at this quote in a new tab)

Direct or indirect comparison of RP-A501 with heart transplantation

No evidence found.

RP-A501 in the pivotal phase 2 trial: route, dose, immunomodulation, and antibody eligibility
AttributeQuoted record
Route and schedule“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.”
Dose“Dose of RP-A501: Cohorts 1, 2 & 3 = 6.7 x10^13 genome copies (GC)/kg; Cohort 4 = 3.8 x10^13 GC/kg.”
Immunomodulation“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.”
Complement inhibitor“Pegcetacoplan was incorporated into the immunomodulation regimen for Cohort 3 but excluded in Cohort 4.”
Antibody eligibility“Anti-AAV9 neutralizing antibody titer >1:40.”
Approved systemic AAV9 comparator: onasemnogene abeparvovec (Zolgensma) label attributes
AttributeQuoted label text
Indication“ZOLGENSMA is an adeno-associated virus (AAV) vector-based gene therapy indicated for the treatment of pediatric patients less than 2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene.”
Route and schedule“For single-dose intravenous infusion only”
Dose“The recommended dosage of ZOLGENSMA is 1.1 × 10¹⁴ vector genomes (vg) per kg of body weight.”
Immunosuppression“Starting one day prior to ZOLGENSMA infusion, administer systemic corticosteroids equivalent to oral prednisolone at 1 mg/kg of body weight per day for a total of 30 days.”
Boxed warning“WARNING: SERIOUS LIVER INJURY and ACUTE LIVER FAILURE”“Cases of acute liver failure with fatal outcomes have been reported.”
Antibody testing“Perform baseline anti-AAV9 antibody testing prior to ZOLGENSMA infusion.”“The safety and efficacy of ZOLGENSMA in patients with anti-AAV9 antibody titers above 1:50 have not been evaluated.”
Liver monitoring“Continue to monitor liver function for at least 3 months after infusion, and at other times as clinically indicated.”
Platelet monitoring“Monitor platelet counts before ZOLGENSMA infusion, and at least weekly for the first month and then every other week for the second and third month or until platelet counts return to baseline.”
Thrombotic microangiopathy“Prompt attention to signs and symptoms of TMA is advised, as TMA can result in life-threatening or fatal outcomes.”
Cardiac monitoring“Consider cardiac evaluation after ZOLGENSMA infusion and consult a cardiologist as needed.”
Approved systemic AAV9 comparator: rebisufligene etisparvovec (Fayuvi) label attributes, approved September 2026
AttributeQuoted label text
Indication“FAYUVI is an adeno-associated virus (AAV) vector-based gene therapy indicated for the treatment of neurologic manifestations of mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo syndrome type A) in pediatric patients with preserved neurodevelopmental function.”
Route and schedule“For single-dose intravenous infusion only.”
Dose“The recommended dose of FAYUVI is 3.0 × 10¹³ vector genomes (vg) per kg body weight.”
Immunosuppression“Starting 1 day prior to infusion, administer corticosteroids for a minimum of 8 weeks.”
Antibody testing“FAYUVI administration is not recommended for patients with elevated anti-AAV9 total binding antibody titers (≥ 1:100)”
Availability of an antibody test“An FDA-authorized test for the detection of anti-AAV9 total binding antibodies is not currently available.”
Liver monitoring“Monitor liver enzymes and total bilirubin levels until 2 weeks after the corticosteroid taper is complete and as clinically indicated.”
Platelet monitoring“Monitor platelet counts weekly for the first 4 weeks, then monthly for 6 months following infusion”
Thrombotic microangiopathy“Thrombotic microangiopathy (TMA) has been reported in association with AAV gene therapies.”
Approved systemic AAVrh74 comparator: delandistrogene moxeparvovec (Elevidys) label attributes
AttributeQuoted label text
Indication“ELEVIDYS is an adeno-associated virus vector-based gene therapy indicated for the treatment of patients 4 years of age and older with Duchenne muscular dystrophy (DMD) who are ambulatory and have a confirmed mutation in the DMD gene.”
Route and schedule“ELEVIDYS is for single-dose intravenous infusion only.”
Dose“Recommended dosage: 10 to 70 kg: 1.33 × 10¹⁴ vector genomes (vg) per kg of body weight; 70 kg or greater: 9.31 × 10¹⁵ vg.”
Immunosuppression“One day prior to infusion, initiate a corticosteroid regimen for a minimum of 60 days.”
Boxed warning“WARNING: ACUTE SERIOUS LIVER INJURY AND ACUTE LIVER FAILURE”“Acute serious liver injury, including life-threatening and fatal acute liver failure, has occurred with ELEVIDYS.”
Antibody testing“Select patients for treatment with ELEVIDYS with anti-AAVrh74 total binding antibody titers <1:400 as measured by an FDA authorized test.”
Liver monitoring“Continue to monitor liver function weekly for the first 3 months after infusion and continue until results are unremarkable.”
Proximity to care“Instruct patients to maintain proximity to an appropriate healthcare facility, as determined by the healthcare provider, for at least 2 months following ELEVIDYS infusion.”
Cardiac monitoring“Acute, serious, life-threatening myocarditis and troponin-I elevations have been observed.”“Monitor troponin-I before ELEVIDYS infusion, and weekly for the first month after ELEVIDYS infusion.”
Infection risk“Serious infections with fatal outcomes may occur due to concomitant administration of corticosteroids, additional immunosuppressants, and ELEVIDYS.”
Approved systemic AAV5 comparator: etranacogene dezaparvovec (Hemgenix) label attributes
AttributeQuoted label text
Indication“HEMGENIX is an adeno-associated virus vector-based gene therapy indicated for the treatment of adults with Hemophilia B (congenital Factor IX deficiency) who:”
Route and schedule“For single-use intravenous infusion only.”
Dose“The recommended dose of HEMGENIX is 2 x 10¹³ genome copies (gc) per kg of body weight.”
Immunosuppression“Consider corticosteroid treatment should elevations occur and as clinically indicated”
Antibodies to the capsid“In AAV-vector based gene therapies, preexisting neutralizing anti-AAV antibodies may impede transgene expression at desired therapeutic levels.”“Following treatment with HEMGENIX all patients developed neutralizing anti-AAV5 antibodies.”
Liver monitoring“Monitor transaminase levels once per week for 3 months and thereafter monthly up to 1 year after HEMGENIX administration to mitigate the risk of potential hepatotoxicity.”
Long-term monitoring“Monitor for hepatocellular carcinomas for five years following administration of HEMGENIX in patients at high risk for hepatocellular carcinoma through abdominal ultrasound screenings and serum alfa-fetoprotein (AFP) levels.”
Published indirect comparison of RP-A501 with another gene therapy

No evidence found.