Interim Study Update for the BB-301 Gene Therapy Phase 1b/2a First in Human Trial in Subjects with Oculopharyngeal Muscular Dystrophy with Dysphagia

Topic:

Clinical Trials

Poster Number: LB461

Author(s):

Jerel Banks, MD, PhD, Benitec Biopharma Inc., Sophie Mukadam, B.A., Benitec Biopharma Inc., Milan Amin, MD, Department of Otolaryngology-Head and Neck Surgery, New York University Langone Voice Center, Efstratios Achlatis, M.D., Department of Otolaryngology-Head and Neck Surgery, New York University Langone Voice Center, Stamatela Balou, Ph.D., CCC-SLP, BCS-S, Department of Otolaryngology-Head and Neck Surgery, New York University Langone Voice Center, Catriona Steele, Ph.D., S-LP(C), CCC-SLP, Swallowing Rehabilitation Research Laboratory, University Health Network, Ontario, Canada, Melanie Peladeau-Pigeon, M.H.Sc., P.Eng., Swallowing Rehabilitation Research Laboratory, University Health Network, Ontario, Canada, Emily Barrett, M.H.Sc., Reg. CASLPO, S-LP (C), Swallowing Rehabilitation Research Laboratory, University Health Network, Ontario, Canada, Dany Meng, H.B.Sc., Swallowing Rehabilitation Research Laboratory, University Health Network, Ontario, Canada

Oculopharyngeal Muscular Dystrophy (OPMD) is a rare, autosomal dominant, late-onset degenerative muscle disorder presenting in patients at 40-60 years of age. OPMD is principally characterized by severe progressive dysphagia, impacting 97% of patients, which can lead to chronic choking, malnutrition, aspiration pneumonia and, in severe cases, death. OPMD is caused by a mutation in the poly(A)-binding protein nuclear 1 (PABPN1) gene.

There is no effective drug therapy available for OPMD. Current interventions are limited to palliative surgical procedures and dietary modifications, which do not address the underlying cause of disease.

BB-301, a novel investigational gene therapy designed to improve the dysphagic symptoms of OPMD, is being evaluated in a Phase 1b/2a, open-label dose escalation study (NCT06185673) to assess safety and clinical activity.

Two causes of dysphagia have been observed in study subjects: excessive accumulation of solid and liquid residue (Total Pharyngeal Residue or “TPR”) remaining post-swallow or “inefficient swallowing”, and recurrent pathologic sequential swallowing (i.e., rapid involuntary contractions of the pharyngeal muscles, between which the resting diameter of the pharynx is not restored) or “ineffective swallowing”. Pathologic sequential swallowing is experienced by subjects as involuntary swallows.

Outcome measures for NCT06185673 include videofluoroscopic swallowing studies for serial assessment of TPR and frequency of pathologic sequential swallowing, and the use of a patient-reported outcome instrument (Sydney Swallow Questionnaire).

Four subjects have been safely treated with the lowest-dose of BB-301, and interim results for the first three subjects for whom data are available are presented here.

Interim study results for the first 3 subjects treated with BB-301 following 12-months, 9-months, and 3-months on treatment, respectively, demonstrate durable, clinically significant reductions in both causes of dysphagic deficits. There have been no Severe Adverse Events in study subjects.

These data represent successful improvements in swallowing function driven by a novel gene therapy for OPMD.