Benitec Biopharma Announces Sustained Swallowing Efficiency Improvements at 180 Days for OPMD Subject Treated with BB-301 in Phase 1b/2a Study

Benitec Biopharma Inc., a clinical-stage biotechnology company specializing in gene therapy, has announced promising interim results from their ongoing Phase 1b/2a clinical trial of BB-301, a gene therapy for Oculopharyngeal Muscular Dystrophy (OPMD). This study includes a single-arm, open-label, sequential, dose-escalation cohort design. BB-301 has received Orphan Drug designation from both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

The latest data, focusing on the 180-day post-dose assessments, indicate significant and continued improvements in swallowing efficiency and reductions in dysphagic symptoms for the first subject treated (Subject 1). These improvements were measured using videofluoroscopic swallowing studies (VFSS), which evaluate Total Pharyngeal Residue (TPR), and the Sydney Swallow Questionnaire (SSQ) for subjective dysphagic symptoms.

Critically, the 180-day post-dose average TPR values for three out of four food types were lower than any values recorded during the 9-month pre-dose observation period of the OPMD Natural History Study. These improvements in TPR suggest a significant reduction in the amount of food or liquid material remaining in the pharynx after swallowing. For the fourth food type, the post-dose TPR values were comparable to the lowest observed values during the pre-dose period.

Furthermore, the Total SSQ Score, which measures the severity of dysphagic symptoms, showed a continued decline at 180 days post-dose, indicating sustained improvements in the subject's ability to swallow. These findings are especially noteworthy because they suggest a lasting positive impact on swallowing function, a critical concern for OPMD patients.

Key Opinion Leaders (KOLs) in the field of OPMD research have highlighted these VFSS and SSQ assessments as essential benchmarks for evaluating clinical improvements in patients. The continued reductions in TPR and SSQ scores at the 180-day mark underscore the potential long-term benefits of BB-301 for improving swallowing efficiency and reducing dysphagic symptoms.

Jerel A. Banks, M.D., Ph.D., Executive Chairman and CEO of Benitec, expressed optimism about the interim results, noting the significant improvements in swallowing function and the reduction in the risk of aspiration, a serious concern for OPMD patients. He also mentioned that the second subject in the study received their dose in February 2024, with plans to dose the third subject in the third quarter of 2024. Further interim results, including data from multiple patients with at least 6 to 12 months of follow-up, are expected in early 2025.

OPMD is a rare, progressive disease caused by mutations in the PABPN1 gene, leading to symptoms such as difficulty swallowing (dysphagia), limb weakness, and drooping eyelids (ptosis). The disease progressively worsens over time, leading to severe complications, including chronic choking, aspiration pneumonia, and potentially death. Current therapeutic options are limited and do not address the underlying genetic cause of the disease.

BB-301 is a novel gene therapy that utilizes a modified AAV9 capsid to deliver a bifunctional construct. This construct co-expresses codon-optimized PABPN1 and two small inhibitory RNAs (siRNAs) designed to silence the mutant PABPN1 while allowing the expression of functional PABPN1. This "silence and replace" mechanism aims to halt the expression of the faulty gene while providing a functional replacement, offering a unique approach to treating OPMD.

Benitec Biopharma Inc. focuses on developing innovative genetic medicines using their proprietary DNA-directed RNA interference (ddRNAi) platform. Their approach combines RNA interference with gene therapy to achieve sustained silencing of disease-causing genes and the delivery of wild-type genes, addressing chronic and life-threatening conditions like OPMD.