Final Tests Planned into Potential Gene Therapy for OPMD, Could Support Trial in Patients

Three new animal-model tests of a potential gene therapy for oculopharyngeal muscular dystrophy (OPMD), known as BB-301, are planned, Benitec Biopharma announced. Results are expected to support a request for a Phase 1 clinical trial in patients.

OPMD results from a faulty PABPN1 gene, leading to a protein that can form insoluble clumps linked with muscle weakness.

BB-301 uses a DNA-directed RNA interference (ddRNAi) strategy. Delivered via a modified, harmless adeno-associated virus (AAV), the therapy is intended to “silence and replace” the mutant protein. It suppresses its production and provides a source of normal, or wild-type, protein to target cells.

A 2017 study showed that this approach significantly reduced the amount of PABPN1 aggregates, restored muscle strength and eased muscle fibrosis (scarring) in mice. Subsequent experiments in cells from OPMD patients confirmed these results.

The preclinical research, to be conducted in a canine disease model, will help to optimize methods of administration, confirm the efficiency of the AAV vector in introducing a healthy gene into key muscle cells, assess optimal dosing, and further characterize toxicological data necessary for regulatory filings and clinical trial design.

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According to the company, these three planned dog studies will support the submission of an Investigational New Drug (IND) application, an essential step in getting regulatory approval to start the trial. Pre-IND application meetings with the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA) and Health Canada took place in 2017.

“Through our continued focus on … BB-301 for the treatment of [OPMD], our team has an unprecedented opportunity to develop a novel genetic medicine that could facilitate clinically meaningful patient benefit,” Jerel A. Banks, MD, PhD, Benitec’s executive chairman and CEO, said in a press release.

The preclinical studies will be done in partnership with a medicine and surgery team with several decades of experience in OPMD treatment, Benitec added.

The FDA granted orphan drug status to BB-301 as a potential OPMD treatment in January 2018. The EMA awarded it similar status in early 2017.