Avidity's DMD Therapy Shows Promise, Paving Way for FDA Submission

Avidity Biosciences has reported encouraging results from two mid-stage trials of its investigational exon-44-skipping therapy for Duchenne muscular dystrophy (DMD), potentially clearing the path for a biologics license application (BLA) to the FDA. The therapy, delpacibart zotadirsen (del-zota), demonstrated significant functional improvements in patients after one year of treatment, reversing disease progression in key metrics.

Robust Biomarker and Functional Improvements

The Phase I/II EXPLORE44 and EXPLORE44-OLE studies, involving 26 and 16 patients respectively, revealed that del-zota increased normal dystrophin production by approximately 25%. Dystrophin concentrations were restored to up to 58% of normal levels. Additionally, the therapy led to a rapid and substantial drop of over 80% in creatine kinase (CK) levels, a key marker of muscle damage, with these reduced levels maintained through 16 months of follow-up.

Importantly, these biomarker improvements correlated with functional benefits. Compared to natural history controls, patients treated with del-zota showed a 2.1-second improvement in the four-stair climb test, contrasting with a 2.7-second decline in untreated patients. Similar positive outcomes were observed in other functional assessments, including the 10-meter walk/run, time to rise from floor, and North Star Ambulatory Assessment tests.

Regulatory Path and Market Potential

Avidity aims to complete a BLA submission by the end of 2025, seeking accelerated approval for del-zota. The company is also preparing a confirmatory trial to support full global approval. Analysts at BMO Capital Markets expect a "smooth" approval process, citing the lack of other approved exon-44 skipping treatments. They estimate an addressable U.S. patient population of around 1,000.

The positive data could potentially accelerate Avidity's transition to a commercial-stage company by 2026. This development may also enhance the company's attractiveness to potential buyers, following reports of acquisition interest from Novartis in August 2025.

Implications for DMD Treatment Landscape

Del-zota's promising results represent a significant advancement in the treatment of DMD, particularly for patients amenable to exon-44 skipping. The therapy's ability to reverse disease progression and improve functional outcomes could set a new standard in DMD care. As Avidity progresses towards regulatory submission, the pharmaceutical industry will be closely watching the potential impact on the broader landscape of genetic therapies for rare diseases.