First-in-human study of golodirsen for Duchenne muscular dystrophy

This first-in-human study of golodirsen showed its long-term safety and biologic activity in patients with Duchenne Muscular Dystrophy (DMD). The approved exon-skipping therapy is designed to enable the production of functional dystrophin proteins, as described in the peer-reviewed journal Nucleic Acid Therapeutics. Click here to read the article.

Golodirsen was tested in ambulatory patients with exon 53 skip amenable DMD. They were at an age associated with progressive deterioration and declining ambulatory function.

Francesco Muntoni, MD, from University College London, and coauthors, on behalf of the SKIP-NMD Study Group, conducted a two-part Phase 1/2 trial of long-term golodirsen treatment. Part 1 included a safety review. Part 2 was a 168-week evaluation of golodirsen 30 mg/kg. The primary endpoints were dystrophin protein expression and a 6-minute walk test. Golodirsen significantly increased dystrophin protein expression 16-fold and exon skipping 28.9-fold. After 3 years, the 6-minute walk test declined by only 99.0 meters for golodirsen-treated patients versus a decline of 181.4 meters for the control group, and loss of ambulation occurred in 2 of 25 golodirsen-treated versus 5 of 19 control patients.

“The results presented herein provide evidence for the biologic activity and long-term safety of golodirsen in a declining DMD population, supporting evaluation of golodirsen in an ongoing Phase 3 trial,” concluded the investigators.

“These long-term clinical outcome data support the contention that systemically administered morpholino oligomers can significantly improve the expected disease course in patients with Duchenne Muscular Dystrophy.” says Executive Editor Graham C. Parker, PhD, The Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Children's Hospital of Michigan, Detroit, MI.

About the Journal

Nucleic Acid Therapeutics is an authoritative peer-reviewed journal published bimonthly in print and online that focuses on cutting-edge basic research, therapeutic applications, and drug development using nucleic acids or related compounds to alter gene expression. The Journal is under the editorial leadership of Co-Editors-in-Chief Bruce A. Sullenger, PhD, Duke Translational Research Institute, Duke University Medical Center and Annemieke Aartsma-Rus, PhD, Leiden University Medical Center, and Executive Editor Graham C. Parker, PhD. Nucleic Acid Therapeutics is the official journal of the Oligonucleotide Therapeutics Society. Complete tables of content and a sample issue may be viewed on the Nucleic Acid Therapeutics website.

About the Society
The Oligonucleotide Therapeutics Society  is an open, non-profit forum to foster academia- and industry-based research and development of oligonucleotide therapeutics. The society brings together the expertise from different angles of oligonucleotide research to create synergies and to bring the field of oligonucleotides to its full therapeutic potential.

About the Publisher

Mary Ann Liebert, Inc., publishers is known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry’s most widely read publication worldwide. A complete list of the firm’s more than 100 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.