Del-Zota Produced Statistically Significant Increases in Exon Skipping and Dystrophin Levels in EXPLORE44: A Phase 1/2 Study in Patients with DMD44

Background/Purpose: Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene. Delpacibart zotadirsen, or del-zota (AOC: 1,044), is an antibody-oligonucleotide conjugate (AOC) comprised of an anti-transferrin receptor 1 (TfR1) antibody conjugated to an exon 44-skipping phosphorodiamidate morpholino oligomer (PMO). Del-zota is designed to restore the dystrophin reading frame and produce functional, internally truncated dystrophin protein in individuals with mutations amenable to exon 44 skipping (DMD44).

Methods: Part B of the Phase 1/2 EXPLORE44® trial (NCT05670730) is a randomized, placebo-controlled, double-blind study assessing safety, tolerability, pharmacokinetics, and exon skipping efficacy of multiple-ascending doses of del-zota. EXPLORE44® enrolled 24 ambulatory and nonambulatory individuals aged 7 to 27 years with DMD44. (Part A: healthy volunteer data has been reported previously).

Results: Treatment with del-zota resulted in consistent and high PMO muscle concentrations and produced significant increases in exon skipping (up to 67%) and dystrophin production (average of 25% and up to 58% of normal) in skeletal muscle and consistent reductions in blood creatine kinase to near normal levels (reduced by >80% compared to baseline). Del-zota produced favorable safety and tolerability results.

Conclusion: The EXPLORE44® trial represents the first-in-patient experience using Avidity Biosciences’ proprietary AOC^TM technology to deliver PMOs to muscle. Del-zota's ability to increase dystrophin production and exon skipping and reduce CK levels highlights its potential to improve the lives of patients with DMD44. These data support the continued evaluation of del-zota in the Phase 2 EXPLORE44-OLE^TM trial (NCT06244082).

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Artikel online veröffentlicht:
26. September 2025