Sarepta Therapeutics

Elevidys, a $3.2 million gene therapy for Duchenne muscular dystrophy, failed to meet its primary endpoint in a Phase 3 trial, showing no significant motor function improvement over placebo.

Delandistrogene moxeparvovec (Elevidys) for Duchenne muscular dystrophy missed primary endpoint in EMBARK trial but showed differences in secondary outcomes, including clinically relevant improvements in time to rise and 10-meter walk/run. FDA granted full approval based on totality of evidence, despite primary endpoint failure.

CGTs disrupt treatment for genetic diseases, with 69 marketed worldwide and 7 novel FDA approvals in 2023. Oncology leads CGTs, projected to reach $37bn by 2030. Outsourcing vs. in-house manufacturing is crucial, with Lonza Group as the leading CMO for marketed CGTs.

Pfizer withdrew Oxbryta from global markets due to increased risk of death, joining other drugs like Aduhelm, Exkivity, Ukoniq, and Zydelig that were approved under the FDA's accelerated pathway but later withdrawn. The pathway, implemented in 1992, has helped bring nearly 300 drugs to market but faces scrutiny over delayed confirmatory trials and surrogate endpoints. Sarepta's Elevidys is an exception, securing full approval despite missing primary efficacy endpoints.

Delandistrogene moxeparvovec (Elevidys) gene therapy for Duchenne muscular dystrophy (DMD) was safe over 5 years, with 75 adverse events, mostly mild or moderate, and no serious AEs. Treated patients showed significant improvements in time to rise (TTR) and 10-meter walk/run time compared to an external control cohort, maintaining ambulation while the control group lost it. The therapy's North Star Ambulatory Assessment (NSAA) total score also improved significantly over 5 years, diverging from natural history predictions.

Rare diseases affect 7% of the world’s population, mostly genetic. Precision medicine offers tailored treatments, overcoming traditional pharmaceutical research limitations. Success stories include therapies for spinal muscle atrophy, Batten’s disease, Duchenne muscular dystrophy, and cystic fibrosis. Challenges remain in cost, ethical considerations, and data sharing, but advancements in genomic sequencing, AI, and digital technology hold promise.

Six clinical-stage biotech companies are advancing Duchenne muscular dystrophy treatments: Wave Life Sciences, Sarepta Therapeutics, Capricor Therapeutics, Edgewise Therapeutics, Italfarmaco, and Avidity Biosciences. These companies focus on various therapeutic approaches, including RNA medicines, gene therapies, myosin inhibitors, and HDAC inhibitors. The global Duchenne treatment market is expected to grow significantly, driven by regulatory approvals and ongoing research.

Wave Life Sciences (WVE) and Sarepta Therapeutics (SRPT) are both high-risk biotech stocks, but Wave offers more potential upside. Wave's lead DMD program shows promising phase 2 data, potentially leading to FDA accelerated approval in 2025. Sarepta, with existing DMD therapies, faces regulatory risks, particularly with the EMA's pending decision on Elevidys. Despite Sarepta's market presence, Wave's potential for significant growth makes it the better investment for risk-tolerant investors.

John Brandsema, MD, discusses ongoing research for Duchenne muscular dystrophy (DMD), including exon skipping agents, PPMOs, sevasemten, cell-based therapies, and gene transfer therapies. He emphasizes the need for further optimization and the importance of newborn screening for early diagnosis.

Sarah Jenssen, with Duchenne muscular dystrophy, faced insurance denial for $3.2 million gene therapy despite FDA approval. After appeal, coverage was granted, highlighting broader issues of FDA standards, insurer decisions, and high drug prices. Elevidys, approved for all ages, faced criticism for limited data on wheelchair users, sparking debates on treatment access and cost-effectiveness.