Treatment with an AOC Shown to Improve Functional Outcomes in Duchenne Muscular Dystrophy
Key Takeaways
- Del-zota was associated with improvements across multiple functional end points vs baseline and natural history in individuals with Duchenne muscular dystrophy amenable to exon 44 skipping.
- There are currently no approved mutation-specific therapies for the 6%-7% of people with Duchenne muscular dystrophy amenable to exon 44 skipping.
- Avidity Biosciences plans to submit a biologics license application (BLA) to the Food and Drug Administration (FDA) for accelerated approval.
Treatment with delpacibart zotadirsan (del-zota; Avidity Biosciences, San Diego, CA), an investigational antibody-oligonucleotide conjugate (AOC), was associated with improvements in functional measures compared with baseline and natural history in individuals with Duchenne muscular dystrophy amenable to exon 44 skipping (DMD44) according to data from the phase 1/2 EXPLORE44 (NCT05670730) and EXPLORE44-OLE (NCT06244082) trials.
EXPLORE44 included 26 individuals with DMD44 who were randomized to receive del-zota 5 mg/kg once every 6 weeks (Q6W) or 10 mg/kg once every 8 weeks (Q8W). Seventeen EXPLORE44 participants were subsequently enrolled in the multicenter EXPLORE44-OLE open-label extension (OLE) and received del-zota 5 mg/kg Q6W. Participants in EXPLORE44 and EXPLORE44-OLE were treated continuously for 1 year. Functional assessment data—including the 4-stair climb (4SC), 10-meter walk/run test (10MWRT), time to rise (TTR), North Star Ambulatory Assessment (NSAA), and Performance of Upper Limb (PUL 2.0)—were compared against a matched subset of data from the PRO-DMD-01 natural history cohort. Not all participants could complete all assessments.
The following key results were reported:
- 4SC improved by 2.1 seconds in those treated with del-zota vs a 2.7-second decline in the natural history group (del-zota, n=10; natural history, n=22).
- 10MWRT improved by 0.7 seconds in those treated with del-zota vs a 1.5-second decline in the natural history group (n=10; n=22).
- TTR improved by 3.2 seconds in those treated with del-zota vs a 1.6-second decline in the natural history group (n=6; n=19).
- NSAA remained stable in those treated with del-zota vs a 2.4-point decline in the natural history group (n=10; n=20).
- PUL 2.0 improved by 1.5 points in both ambulatory and nonambulatory participants treated with del-zota vs a 0.7-point decline in the natural history group (n=17; n=27).
- Most treatment-emergent adverse events (TEAEs) were mild to moderate and included upper respiratory tract symptoms, diarrhea, fall, back pain, and headache. One participant discontinued EXPLORE44-OLE due to hypersensitivity.
Source: Avidity Biosciences. Avidity Biosciences' del-zota demonstrated reversal of disease progression across key functional endpoints in EXPLORE44® and EXPLORE44-OLE™ Phase 1/2 trial in people living with DMD44. Press release. Published September 10, 2025. Accessed March 15, 2026. https://www.prnewswire.com/news-releases/avidity-biosciences-del-zota-demonstrated-reversal-of-disease-progression-across-key-functional-endpoints-in-explore44-and-explore44-ole-phase-12-trial-in-people-living-with-dmd44-302552339.html