Elevidys (delandistrogene moxeparvovec-rokl) / Sarepta Therap, Nationwide Children's, Roche - LARVOL DELTA

The latest developments in synthetic approaches to duchenne muscular dystrophy. (PubMed, Expert Rev Neurother) - "Although corticosteroids remain the standard treatment, newly approved drugs such as exon-skipping therapies, vamorolone, delandistrogene moxeparvovec, and givinostat provide new treatment options...The accelerated FDA review process has enabled faster approval of new medications; however many have provided minimal clinical benefit to patients. Despite these challenges, continued drug development and innovative research offer hope to patients."

Journal • Review • Cardiomyopathy • Cardiovascular • Duchenne Muscular Dystrophy • Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Muscular Dystrophy • Respiratory Diseases

Roche announces new results from EMBARK demonstrating significant sustained benefits of Elevidys in ambulatory individuals with Duchenne muscular dystrophy (DMD) (Roche Press Release) - P3 | N=126 | EMBARK (NCT05096221) | Sponsor: Sarepta Therapeutics, Inc. | "Roche...announced today positive topline results from year two of the EMBARK trial....Two years after treatment with Elevidys, statistically significant and clinically meaningful improvements were observed across three key motor function measures of NSAA, TTR and 10MWR, when compared to a pre-specified propensity-weighted untreated external control group. Functional differences between individuals treated with Elevidys and those in the external control group increased between one and two years after dosing....No new safety signals observed further reinforcing the consistent and manageable safety profile observed with Elevidys to date....Detailed results from year two of the EMBARK study will be shared at an upcoming medical meeting and discussed with health authorities."

P3 data: top line • Duchenne Muscular Dystrophy

Is duchenne gene therapy a suitable treatment despite its immunogenic class effect? (PubMed, Expert Opin Drug Saf) - "The FDA's recent approval of delandistrogene moxeparvovec (Elevidys) underscores the promise of gene replacement therapies for dystrophin restoration in DMD patients...CRISPR/Cas9 therapies, while promising, face significant regulatory and safety challenges that hinder their clinical application. Optimal DMD therapies should target both skeletal and cardiac muscles to be truly effective."

Journal • Review • Cardiomyopathy • Cardiovascular • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

EMBARK: A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in Participants With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P3 | N=126 | Completed | Sponsor: Sarepta Therapeutics, Inc. | Active, not recruiting ➔ Completed

Trial completion • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

ENVOL: A Gene Delivery Study to Evaluate the Safety and Expression of Delandistrogene Moxeparvovec in Participants Under the Age of Four With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P2 | N=21 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Nov 2032 ➔ May 2033

Trial completion date • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Acute Liver Injury Following Delandistrogene Moxeparvovec Gene Therapy Requiring Intravenous Immunoglobulin. (PubMed, Pediatr Neurol) - No abstract available

Gene therapy • Journal • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Hepatology • Liver Failure • Muscular Dystrophy

Neuromuscular diseases: genomics-driven advances. (PubMed, Genomics Inform) - "In spinal muscular atrophy (SMA), therapies like nusinersen, onasemnogene abeparvovec, and risdiplam have dramatically improved patient outcomes. Similarly, Duchenne muscular dystrophy (DMD) has seen significant progress, most notably with the FDA approval of delandistrogene moxeparvovec, the first micro-dystrophin gene therapy. Despite these advancements, challenges remain, including the rarity of many NMDs, genetic heterogeneity, and the high costs associated with genomic technologies and therapies. Continued progress in gene therapy, RNA-based therapeutics, and personalized medicine holds promise for further breakthroughs in the management of these debilitating diseases."

Journal • Review • CNS Disorders • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Muscular Dystrophy • Rare Diseases

Long-Term Survival and Myocardial Function Following Systemic Delivery of Delandistrogene Moxeparvovec in DMDMDX Rats. (PubMed, Hum Gene Ther) - "Transgene expression was maintained up to >25 months and micro-dystrophin expression was broadly distributed across skeletal and cardiac muscle. Taken together, these findings demonstrate long-term cardiac efficacy and improved survival following delandistrogene moxeparvovec treatment in DMDMDX rats."

Journal • Preclinical • Cardiomyopathy • Cardiovascular • Duchenne Muscular Dystrophy • Fibrosis • Gene Therapies • Genetic Disorders • Heart Failure • Immunology • Muscular Dystrophy

Willingness to Pay for Ultra-Rare Diseases in US, Germany, France, UK, and Japan: A Comparative Study (ISPOR-EU 2024) - "Elevidys (DMD) with a WAC price of $3.2 million in US and Upstaza (AADC deficiency) with a list price of €3.5million in France are amongst the highest priced treatments globally... WIP for treatments for ultra rare diseases specifically gene therapies is very high and HTA institutions and payers have recognised the value of curative treatments reflected through positive HTA and price outcomes."

Gene Therapies • Genetic Disorders • Pediatrics • Rare Diseases

What Are the Key Themes and Sentiments Captured Through Social Listening in Response to Recent Changes in the Duchenne Muscular Dystrophy Treatment Landscape? (ISPOR-EU 2024) - " Using a social media listening platform (Brandwatch), we assessed the difference in stakeholder sentiment before and after the fordadistrogene movaparvovec announcement (June 12 th 2024), and after the announcement of the delandistrogene moxeparvovec-rokl approval (June 20 th 2024). The variability in sentiment in the DMD population over a relatively short time period confirms the ability of social media listening to capture patient perspectives quickly. However, this variability in sentiment over a 10 day time-period also points to a need for methodological scrutiny to reduce bias in social media listening data collection."

Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Caregiver Global Impression Observations from EMBARK: A Phase 3 Study Evaluating Delandistrogene Moxeparvovec in Ambulatory Patients with Duchenne Muscular Dystrophy. (PubMed, Neurol Ther) - P3 | "These exploratory findings captured by caregiver-reported outcomes add to the totality of evidence that supports the clinical benefits of delandistrogene moxeparvovec for patients with DMD."

Clinical • Journal • P3 data • CNS Disorders • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Response to Hamid et al., "Equitable Access of Delandistrogene Moxeparvovec for Patients With Duchenne Muscular Dystrophy". (PubMed, Pediatr Neurol) - No abstract available

Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

HORIZON: A Gene Transfer Therapy to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) Following Therapeutic Plasma Exchange (Plasmapheresis) in Participants With Duchenne Muscular Dystrophy (DMD) and Pre-existing Antibodies to AAVrh74 (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Sarepta Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

AAV gene therapy for Duchenne muscular dystrophy: the EMBARK phase 3 randomized trial. (PubMed, Nat Med) - P3 | "Safety was manageable and consistent with previous delandistrogene moxeparvovec trials. ClinicalTrials.gov: NCT05096221."

Gene therapy • Journal • P3 data • CNS Disorders • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

HORIZON: A Gene Transfer Therapy to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) Following Therapeutic Plasma Exchange (Plasmapheresis) in Participants With Duchenne Muscular Dystrophy (DMD) and Pre-existing Antibodies to AAVrh74 (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Sarepta Therapeutics, Inc.

New P1 trial • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

ENVISION: A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in Non-Ambulatory and Ambulatory Participants With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P3 | N=148 | Recruiting | Sponsor: Sarepta Therapeutics, Inc. | Trial completion date: Jan 2027 ➔ Jun 2028 | Trial primary completion date: Jan 2026 ➔ May 2027

Trial completion date • Trial primary completion date • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

ENDEAVOR: A Gene Transfer Therapy Study to Evaluate the Safety of and Expression From Delandistrogene Moxeparvovec (SRP-9001) in Participants With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P1 | N=55 | Active, not recruiting | Sponsor: Sarepta Therapeutics, Inc. | Enrolling by invitation ➔ Active, not recruiting | Trial primary completion date: Nov 2024 ➔ Jul 2024

Enrollment closed • Trial primary completion date • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

The FDA approval of delandistrogene moxeparvovec-rokl for duchenne muscular dystrophy: a critical examination of the evidence and regulatory process. (PubMed, Expert Opin Biol Ther) - No abstract available

FDA event • Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Chugai Files Elevidys (SRP-9001) as a Gene Therapy Product for Duchenne Muscular Dystrophy in Japan (Chugai Press Release) - "Chugai Pharmaceutical Co....announced today that it filed a regulatory application with the Ministry of Health, Labour and Welfare (MHLW) for delandistrogene moxeparvovec, a gene therapy product under development (development code: SRP-9001, overseas product name: Elevidys), for the treatment of Duchenne muscular dystrophy (DMD)....The application is based on the results from the global Phase III clinical study (EMBARK)..."

Japan filing • Duchenne Muscular Dystrophy

In brief: Expanded indication for Elevidys. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) Following Imlifidase Infusion in Participants With Duchenne Muscular Dystrophy (DMD) Determined to Have Pre-existing Antibodies to Recombinant Adeno-Associated Virus Serotype (rAAVrh74) (clinicaltrials.gov) - P1 | N=6 | Enrolling by invitation | Sponsor: Sarepta Therapeutics, Inc. | Active, not recruiting ➔ Enrolling by invitation

Enrollment open • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Equitable Access of Delandistrogene Moxeparvovec for Patients With Duchenne Muscular Dystrophy: A Call for Discussion. (PubMed, Pediatr Neurol) - No abstract available

Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Validity of remote live stream video evaluation of the North Star Ambulatory Assessment in patients with Duchenne muscular dystrophy. (PubMed, PLoS One) - P1/2 | "Participants in this analysis received delandistrogene moxeparvovec (as part of SRP-9001-101 [Study 101; NCT03375164] or SRP-9001-102 [Study 102; NCT03769116]) or were randomized to receive placebo (in Part 1 of Study 102)...The results showed that scores from remote functional assessment of patients with Duchenne muscular dystrophy strongly correlated with those obtained in person. These findings demonstrate congruence between live stream remote and in-person functional assessment and suggest that remote assessment has the potential to reduce the burden on a family by supplementing in-clinic visits."

Clinical • Journal • Video • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

How safe is gene therapy? : Second death after Duchenne therapy (PubMed, Inn Med (Heidelb)) - "Although gene therapy applications of AAV vectors are generally considered safe, the systemic administration of high vector doses can lead to severe side effects with a potentially fatal outcome in individual patients, especially after activation of the immune system. In the future, new methods for immunosuppression, reduction of AAV dose and alternative vectors will therefore increasingly come to the fore."

Gene therapy • Journal • Review • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Immunomonitoring requirements in AAV based gene therapy clinical trials: where do we stand? (ESGCT 2023) - "Promising results have been obtained with several rAAV products as illustrated by six drugs currently approved (Luxturna, Zolgensma, Roctavian, Hemgenix, Upstaza and Elevidys) in Europe and USA...Finally, we will describe the general work-flow to implement clinical immune monitoring, in line with Good Clinical Laboratory Practices (GCLP) and other regulatory guidelines. Beyond the method validation itself, other steps, such as definition of responsibilities, personnel training or data and material traceability have to be implemented and controlled by the immunology laboratory to assess safety and efficacy endpoints, while ensuring the quality and integrity of the data."

Clinical • Gene therapy • Gene Therapies