Defeat Duchenne Canada is pleased to inform our community that Avidity Biosciences has shared the positive safety and effectiveness data from their Phase 1/2 study of AOC 1044, their investigational product which is also called delpacibart zotadirsen or del-zota. Del-zota is an Antibody Oligonucleotide Conjugate, a type of medicine that combines a monoclonal antibody (a protein made in a laboratory that acts like protein that occurs naturally in our bodies) and an oligonucleotides (short strands of DNA or RNA). Del-zota is designed to deliver phosphorodiamidate morpholino oligomers (PMOs, a molecule that is used to modify how a gene works) to skeletal muscle and heart tissue to specifically skip exon 44 of the dystrophin gene. The aim of del-zota is to increase the production of dystrophin for people with DMD who have mutations impacting exon 44.
In the EXPLORE44 study, del-zota was found to be well tolerated and have an impact on several indicators of DMD. There was a large increase in muscle concentrations of del-zota after three 5 mg/kg doses, which indicates that the medicine is effectively getting to the muscle it is meant to impact. There were statistically significant (a term that means the change is large enough to be considered an “real” effect of the treatment) increases in exon 44 skipping, with the increase being higher after 4 months of treatment. The EXPLORE44 study also evaluates the amount of creatine kinase (CK), an enzyme found in skeletal muscle and parts of the heart and brain, in the blood that is elevated for people with DMD as it is lost through damaged muscles. People with DMD treated with del-zota in this study had a reduction of blood CK levels to near normal, also indicating impact of treatment.
“This is an exciting moment as these data suggest del-zota has the potential to change the treatment paradigm and course of disease for patients with Duchenne muscular dystrophy mutations amenable to exon 44 skipping. We have not seen this level of dystrophin production and reduction in creatine kinase with other PMO exon-skipping treatments.”
Diana Castro, M.D., Board Certified Neurologist and Neuromuscular Physician, Founder and Director Neurology and Neuromuscular Care Center, Founder and Director Neurology Rare Disease Center and EXPLORE44 trial program investigator.
Avidity is having a webinar to further share information about del-zota and results of their trial on Friday, August 16 at 12 p.m. ET. The DMD community is invited to register using the link below.
Defeat Duchenne Canada looks forward to further updates from Avidity Biosciences and will share them with our audience as they become available. Please read the full press release below.
About AOC 1044
AOC 1044 is currently in Phase 1/2 development as part of the EXPLORE44™ trial for the treatment of DMD mutations amenable to exon 44 skipping. Data from the Phase 1/2 EXPLORE44 trial showed that AOC 1044 delivered unprecedented concentrations of PMO in skeletal muscle with up to 50-times greater concentrations of PMO in skeletal muscle following a single dose compared to peptide conjugated PMOs in healthy volunteers. AOC 1044 was well tolerated, demonstrated statistically significant exon 44 skipping compared to placebo of up to 1.5% in healthy volunteers after a single dose of 10 mg/kg AOC 1044 and increased exon skipping in all participants. Avidity plans to provide a first look at AOC 1044 data in people living with DMD44 in 2H 2024.
Want to know more about Duchenne Research?
Scientists and medical experts have been tirelessly pursuing diverse approaches to defeat Duchenne muscular dystrophy. From tackling the root cause to alleviating symptoms, the field of research is vast and promising. Explore the various strategies being developed and tested, and gain insights into the future of muscular dystrophy treatment: