Benitec Biopharma is making strides in the treatment of Oculopharyngeal Muscular Dystrophy (OPMD) related dysphagia with its gene therapy candidate, BB-301. Interim data from an ongoing Phase 1b/2a clinical trial (NCT06185673) reveals promising improvements in swallowing function among the first patients treated. The trial, conducted at a single site in New York City, is evaluating the safety and clinical activity of BB-301 in individuals with moderate dysphagia resulting from OPMD.
BB-301: A Novel Approach to OPMD Treatment
BB-301 employs a "silence and replace" strategy, utilizing DNA-directed RNA interference (ddRNAi) to target the mutated PABPN1 gene responsible for OPMD. The therapy aims to silence the faulty gene while simultaneously introducing a functional version of the protein. This dual mechanism is designed to halt the progression of the disease and restore normal cellular function.
Clinical Trial Update
As of early February 2025, five participants have been safely administered the low dose of BB-301. Interim results from the first two subjects, assessed at 9 and 6 months post-treatment respectively, showcased durable and clinically significant reductions in dysphagic deficits. These improvements encompass both reduced Total Pharyngeal Residue (TPR) and decreased frequency of pathologic sequential swallowing. Enrollment is ongoing, with a sixth subject anticipated to receive the low dose in the second quarter of 2025. Benitec plans to escalate to a higher dose cohort later in the year.
Expert Commentary
Jerel A. Banks, M.D., Ph.D., Executive Chairman and Chief Executive Officer of Benitec, expressed optimism about the potential of BB-301. "In 2024 the interim clinical study data demonstrated durable, clinically meaningful improvements in swallowing function for the first Subjects safely treated with BB-301, and we remain highly optimistic about the potential for continued benefit in Subjects enrolled in the ongoing clinical study," said Banks. He also acknowledged the strong support from the participants and their families, emphasizing their continued participation in the BB-301 clinical development program.
OPMD and the Need for Effective Therapies
OPMD is a rare, autosomal dominant, late-onset degenerative muscle disorder typically manifesting between 40 and 60 years of age. A hallmark of OPMD is severe progressive dysphagia, affecting approximately 97% of patients. This swallowing difficulty can lead to life-threatening complications such as chronic choking, malnutrition, and aspiration pneumonia. Currently, treatment options are limited to palliative measures like surgical procedures and dietary modifications, which do not address the underlying genetic cause of the disease.
Upcoming Presentation
Benitec Biopharma will present an interim study update at the 2025 Muscular Dystrophy Association Clinical & Scientific Conference in Dallas, TX. The late-breaking oral presentation, titled "Interim Study Update for the BB-301 Gene Therapy Phase 1b/2a First in Human Trial in Subjects with Oculopharyngeal Muscular Dystrophy with Dysphagia," is scheduled for March 19, 2025.
