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 therapyDisease descriptionBurden of Danon disease

Economic impact of diagnostic testing

16 evidence topics · 14 sources

Genetic testing as the confirmatory diagnostic test

“In addition to further phenotypic testing that includes the aforementioned diagnostics, confirmatory genetic testing is critical for diagnosis.” (opens the source at this quote in a new tab)

“Given variable age- and sex-dependent penetrance and expressivity of Danon disease, clinical diagnoses should be confirmed by genetic testing (Figure 2).” (opens the source at this quote in a new tab)

“All patients with suspected Danon disease should undergo genetic testing.” (opens the source at this quote in a new tab)

“Familial cascade testing Genetic testing for relatives of an individual affected by Danon disease is imperative for proper risk assessment and determination of recurrence risk.” (opens the source at this quote in a new tab)

Test content: LAMP2 sequencing with deletion and duplication analysis, alone or within a cardiomyopathy panel

“This reinforces the inclusion of LAMP2 on multigene panels for common inherited cardiomyopathy for both adult and pediatric populations.” (opens the source at this quote in a new tab)

“However, it is imperative that clinicians also consider the less common copy number variants, which may be causative, and ensure that gene targeted deletion/duplication analysis is also performed.” (opens the source at this quote in a new tab)

“Sequencing with deletion/duplication analysis is the industry standard for most commercial laboratories at this time.” (opens the source at this quote in a new tab)

“Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing) depending on the phenotype.” (opens the source at this quote in a new tab)

“Sequence analysis of LAMP2 detects missense, nonsense, and splice site variants and small intragenic deletions/insertions.” (opens the source at this quote in a new tab)

“If no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications.” (opens the source at this quote in a new tab)

“A cardiomyopathy or myopathy multigene panel that includes LAMP2 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype.” (opens the source at this quote in a new tab)

Tissue-based LAMP-2 protein assays: availability

“Note: (1) Muscle biopsy is not required to make the diagnosis; (2) tissue staining demonstrating absence of the LAMP-2 protein can confirm the diagnosis, although this assay is not widely available on a clinical basis.” (opens the source at this quote in a new tab)

“Skeletal and myocardial tissue biopsies can be performed in circumstances when variants of unknown significance are identified in genetic testing and there is diagnostic uncertainty.” (opens the source at this quote in a new tab)

Genetic confirmation as a trial eligibility requirement

“RP-A501-0123 will enroll subjects ≥ 8 years of age with a pathogenic or likely pathogenic LAMP2 variant.” (opens the source at this quote in a new tab)

“Key Inclusion Criteria: Documentation of a pathogenic or likely pathogenic variant of the LAMP2 gene.” (opens the source at this quote in a new tab)

Sponsored no-charge genetic testing and counseling program for suspected Danon disease

“Sponsored, no-charge genetic testing” (opens the source at this quote in a new tab)

“Through the program, individuals suspected of having Danon Disease have access to genetic testing and counseling to help bring them one step closer to a diagnosis and the appropriate clinical management.” (opens the source at this quote in a new tab)

“No patients, healthcare professionals, or payers, including government payers, are billed for this program.” (opens the source at this quote in a new tab)

“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)

“This service is made available by Labcorp Genetics at no charge as part of the program.” (opens the source at this quote in a new tab)

“While third parties and commercial organizations may provide financial support for this program, tests and services are performed by Labcorp Genetics Inc.” (opens the source at this quote in a new tab)

“Third parties and commercial organizations may receive de-identified (pseudonymized) patient data from this program, but at no time would they receive patient identifiable information.” (opens the source at this quote in a new tab)

Population figure stated on the sponsored testing program page

“Approximately 15,000 patients in the United States are living with Danon Disease” (opens the source at this quote in a new tab)

Commercial cardiomyopathy panel that includes Danon disease: size and billing

“Test code: 02251 • Up to 121 genes” (opens the source at this quote in a new tab)

“In addition to insurance billing, this test is also available through one of our genetic testing access programs.” (opens the source at this quote in a new tab)

“Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).” (opens the source at this quote in a new tab)

Genetic testing rates in cardiomyopathy and identified United States patients: company presentation, October 2026
PopulationGenetic testing rate
Adults with hypertrophic cardiomyopathy“1.6%”
Adults with cardiomyopathy, age 40 or younger“2.6%”
Pediatric cardiomyopathy“13.8%”

“Over 900 Identified US Danon Disease Patients” (opens the source at this quote in a new tab)

“Representing a current diagnosis rate under 10%” (opens the source at this quote in a new tab)

“Data as of July 2026; over 80% of patients reported in ICD-10 code and genetic testing lab data have been identified in the last 5 years; ICD-10 code for Danon available from Q4 2023.” (opens the source at this quote in a new tab)

“Aspiration: every person with HCM or a Danon disease signature and every at-risk relative of a confirmed Danon patient is genetically evaluated so no Danon diagnosis is missed” (opens the source at this quote in a new tab)

Diagnostic yield of no-charge sponsored cardiomyopathy and arrhythmia panel testing in 4782 participants

“Importance Genetic testing can guide management of both cardiomyopathies and arrhythmias, but cost, yield, and uncertain results can be barriers to its use.” (opens the source at this quote in a new tab)

“A positive result (molecular diagnosis) was confirmed in 954 of 4782 patients (19.9%).” (opens the source at this quote in a new tab)

“Cascade testing of family members yielded 402 of 958 positive results (42.0%).” (opens the source at this quote in a new tab)

“Overall, 2446 of 4782 patients (51.2%) had only variants of uncertain significance.” (opens the source at this quote in a new tab)

Cost-effectiveness of genetic testing in families with hypertrophic or dilated cardiomyopathy: Australian models

“METHODS: A probabilistic Markov decision model was used to determine cost per quality-adjusted life-year and cost for each life-year gained when genetic testing is included in the management of Australian families with HCM, compared with the conventional approach of periodic clinical screening alone.” (opens the source at this quote in a new tab)

“As the cost of proband genetic testing decreased, the ICER decreased and was cost saving when the cost fell below $A248 (£161 or €185).” (opens the source at this quote in a new tab)

“CONCLUSIONS: The addition of genetic testing to the management of HCM families is cost-effective in comparison with the conventional approach of regular clinical screening.” (opens the source at this quote in a new tab)

“Results The incremental cost per additional QALY of cascade genetic testing prior to periodical clinical surveillance of first-degree relatives compared with periodical clinical surveillance alone was estimated at approximately AUD $6100.” (opens the source at this quote in a new tab)

“At established thresholds of cost-effectiveness, there is a 90% probability that cascade genetic testing is cost-effective.” (opens the source at this quote in a new tab)

Commercial payer coverage criteria for cardiomyopathy gene panels, effective September 2026

“Targeted Panel testing of five or more genes for the diagnosis of a heritable cardiomyopathy is proven and medically necessary in an individual with a confirmed or suspected diagnosis of any of the following conditions:” (opens the source at this quote in a new tab)

“Hypertrophic cardiomyopathy without an identifiable cause (e.g., valvular disease, hypertension, infiltrative or neuromuscular disorder)” (opens the source at this quote in a new tab)

“All other genetic testing for cardiomyopathies, arrhythmias, or aortic vascular disease is unproven and not medically necessary due to insufficient evidence of efficacy.” (opens the source at this quote in a new tab)

“Pretest genetic counseling is recommended to inform persons being tested about the advantages and limitations of the test as applied to their unique situation.” (opens the source at this quote in a new tab)

Procedure code for hereditary cardiomyopathy panel sequencing

“Hereditary cardiomyopathy (e.g., hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy), genomic sequence analysis panel, must include sequencing of at least 5 cardiomyopathy-related genes (e.g., DSG2, MYBPC3, MYH7, PKP2, TTN)” (opens the source at this quote in a new tab)

Florida Medicaid independent laboratory fee schedule, January 2026: rate for code 81439
Procedure codeFee schedule amount as printed
81439“392.06”

“The fees reimbursed below are for services to recipients of all ages.” (opens the source at this quote in a new tab)

Medicare Clinical Laboratory Fee Schedule payment rate for LAMP2 or cardiomyopathy panel testing

No evidence found.

Anti-AAV9 antibody testing as an eligibility test

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

“Perform testing for the presence of anti-AAV9 antibodies.” (opens the source at this quote in a new tab)

“An FDA-authorized test for the detection of anti-AAV9 total binding antibodies is not currently available.” (opens the source at this quote in a new tab)

“Currently available tests may vary in accuracy and design.” (opens the source at this quote in a new tab)

“Perform baseline anti-AAV9 antibody testing prior to ZOLGENSMA infusion.” (opens the source at this quote in a new tab)

“Retesting may be performed if anti-AAV9 antibody titers are reported as > 1:50” (opens the source at this quote in a new tab)

Published cost of anti-AAV9 antibody testing

No evidence found.

Endomyocardial biopsy as the expression assessment in the pivotal trial

“Myocardial tissue expression of LAMP2 protein improved from baseline to ≥ Grade 1 (by IHC), AND, ≥ 10% decrease in LVMI from baseline.” (opens the source at this quote in a new tab)

“The semi-quantitative grading reflects the extent of LAMP2 protein expressing cardiomyocytes in the entirety of biopsy sample according to the scale.” (opens the source at this quote in a new tab)

Endomyocardial biopsy in United States heart transplant recipients: paid amounts and complications in claims data, 2016 to 2019

“Differences in EMB paid amounts and utilization patterns were assessed for commercial payers and Medicare (2016-2019).” (opens the source at this quote in a new tab)

“In 2019, the median paid amount for an outpatient EMB in a heart transplant patient was US $7,918 (commercial) and US $2,980 (Medicare).” (opens the source at this quote in a new tab)

“Approximately 25% of EMB procedures were associated with complications.” (opens the source at this quote in a new tab)

“In 2019, the total median cost of EMB complications per patient was US $9,049.” (opens the source at this quote in a new tab)