Benitec Biopharma announced positive interim data from its Phase 1b/2a clinical trial of BB-301, a gene therapy for oculopharyngeal muscular dystrophy (OPMD), at the 29th Annual Congress of the World Muscle Society in Prague. The investigational adeno-associated virus (AAV) vector-based therapy, designed to silence and replace the mutated PABPN1 gene, demonstrated clinically significant improvements in swallowing function in the first two treated patients.
Clinical Improvements in Swallowing
The trial (NCT06185673) assessed BB-301's impact on dysphagia, a key symptom of OPMD. The first patient, with 270 days of post-treatment follow-up, experienced a 35% reduction in the total score on the Sydney Swallow Questionnaire (SSQ). This patient also showed improvements in videofluoroscopic swallowing study (VFSS) assessments of total pharyngeal residue (TPR), with a 33% improvement for thin liquids, 18% for solid food, and 30% for thick liquids, compared to their natural history study averages.
The second patient, followed for 180 days post-treatment, achieved an 89% improvement in the SSQ Total Score, reaching a score indicative of normal swallowing. This patient also showed a 92% reduction in the frequency of low-volume sequential swallows, as evaluated by VFSS.
BB-301 Mechanism and Trial Design
BB-301 utilizes Benitec's DNA-directed RNA interference (ddRNAi) platform. It consists of a bifunctional construct that expresses a codon-optimized copy of the PABPN1 gene and two small inhibitory RNAs (siRNAs) designed to silence the expression of the mutant PABPN1 gene. The therapy is delivered via a novel AAV9 vector.
The ongoing Phase 1b/2a trial is a single-arm, open-label, sequential, dose-escalation study. Both patients received the low dose of BB-301 (1.2x1013 vg/subject). No significant adverse events were reported.
Management Perspective
"We are highly encouraged by the significant, clinically meaningful improvements observed for both subjects treated at the low-dose of BB-301, with Patient 2 achieving a clinically normal swallowing profile based on the results of the SSQ," said Jerel A. Banks, MD, PhD, Executive Chairman and CEO of Benitec Biopharma. He added, "We look forward to enrolling additional subjects at the next, higher doses of BB-301 in 2025."
