Phase 1/2a Findings Lend Support for BB-301 in Oculopharyngeal Muscular Dystrophy

In recent news, Benitec Biopharma announced positive topline data from a small group of patients in its phase 1b/2a trial (NCT06185673) testing investigational BB-301 as a treatment for dysphagia in oculopharyngeal muscular dystrophy (OPMD), a condition with no FDA-approved therapies. For a single participant who completed 24 months of treatment, study authors began to observe robust, disease-modifying impacts across various questionnaires and outcomes reflective of OPMD.¹

In this open-label, dose-escalation study, 4 patients completed 12 months of treatment of BB-301, an AAV9 vector-based gene therapy that uses a “silence-and-replace” strategy targeting PABPN1, the root cause of OPMD. In the latest update, Benitec shared efficacy and safety data for all 4 patients at the 12-month mark, as well as one individual patient who completed 24 months of treatment. Overall, all 4 patients demonstrated a durable response to BB-301, further supporting its development in a later-stage study.

Pharyngeal Area at Maximum Constriction (PhAMPC), assessed by VFSS, serves as a functional marker of pharyngeal constrictor muscle performance during swallowing. In Patient 1, PhAMPC improved by 27% at 12 months post-treatment versus the final pre-treatment assessment, reflecting more effective throat closure at peak swallow. This functional gain was perfectly maintained at 24 months, indicating a durable improvement in pharyngeal muscle function.

Normalized Residue Ratio Scale–Valleculae (NRRSv), assessed by VFSS, quantifies post-swallow residue remaining in the vallecular region, which is clinically relevant given its association with increased aspiration risk. In Patient 1, NRRSv improved by 35% at 12 months post-treatment versus the final pre-treatment assessment, indicating reduced post-swallow residue. This effect deepened over time, with a 60% reduction in NRRSv at 24 months, reflecting continued improvement in swallowing efficiency for both liquids and solids following BB-301 administration.

“Progressive dysphagia is the most severe, life-threatening complication of OPMD, and we are extremely excited to observe safe, durable, disease-modifying outcomes for the patients treated with BB-301,” Jerel A. Banks, MD, PhD, executive chairman and chief executive officer at Benitec, said in a statement. “Durable improvements in the dysphagic symptom burden can have a profound impact on the lives of patients living with OPMD, and we remain singularly focused on advancing BB-301 through development to improve the lives of all OPMD patients.”

At 24 months post-treatment, Patient 1 continued to demonstrate meaningful improvements in throat-emptying ability for both liquids and solid foods. Compared with the final pre-treatment assessment, Total Pharyngeal Residue (TPR) improved by 32% at 12 months and deepened to a 39% reduction at 24 months, reflecting sustained gains in swallowing efficiency following BB-301. Patient-reported outcomes showed a parallel, progressive benefit over time. Sydney Swallow Questionnaire (SSQ) total scores improved by 64% at 12 months versus pre-treatment baseline, with the reduction in dysphagic symptom burden further strengthening to 78% at 24 months. Collectively, these findings suggest durable and continuing functional and symptomatic improvements through 2 years post dosing.

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OPMD is a late-onset, progressive neuromuscular disorder most commonly caused by a pathogenic polyalanine expansion in the PABPN1 gene, leading to intranuclear protein aggregation and gradual skeletal muscle dysfunction. Clinically, OPMD is defined by slowly worsening ptosis and dysphagia, with many patients also developing proximal limb weakness (often later in the disease course). To date, there are no FDA-approved therapies to treat OPMD or dysphagia-related symptoms.

Banks added, “We look forward to engaging with the U.S. Food and Drug Administration (FDA) in mid-2026 to confirm the BB-301 pivotal study design and continuing to present interim clinical results at future medical conferences. We extend our deepest gratitude to the patients and families participating in the clinical study and to the investigators and clinical teams for their dedication to advancing new treatment options.”

After the 12-month follow-up, each study completer (n = 4) was evaluated across five prespecified response categories that are statistically characterized and combined into a single scoring framework (maximum score of 5), with responder status assigned to patients meeting criteria in at least 2 of 5 categories (≥40%). These included patient-reported oropharyngeal dysphagia, assessed through SSQ total score, other VFSS assessments, and functional swallowing capacity, evaluated through Cold-Water Timed Drinking Test (CWDT).

Overall, results showed that all cohort 1 completers were formal responders to BB-301 after 12 months of treatment. Of the 4 patients, 3 had total responder scores of 4 and 1 had a total responder score of 3. All patients met the response criteria for SSQ and PhAMPC, with most achieving response on pharyngeal residue and sequential swallowing.

REFERENCE
1. Benitec Biopharma Provides Positive Long-Term Clinical Study Results for BB-301 Phase 1b/2a Clinical Trial Demonstrating Robust Efficacy and Continued Durability of Response. News release. Benitec Biopharma. January 11, 2026. Accessed January 22, 2026. https://www.benitec.com/for-investors/news-events/press-releases/detail/141/benitec-biopharma-provides-positive-long-term-clinical-study-results-for-bb-301-phase-1b2a-clinical-trial-demonstrating-robust-efficacy-and-continued-durability-of-response