Benitec Biopharma’s Oculopharyngeal Muscular Dystrophy Gene Therapy Trial Doses First Patient

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Benetic anticipates an announcement of interim results sometime around the midpoint of 2024.

Benitec Biopharma’s phase 1b/2a clinical trial (NCT identifier pending) evaluating BB-301, its investigational adeno-associated virus (AAV) vector-based silence and replace gene therapy for the treatment of oculopharyngeal muscular dystrophy (OPMD)-related dysphagia, has dosed its first patient.1

BB-301 is administered directly to the pharyngeal constrictor muscles in a single day. The company noted that the first patient dosed will be followed for 52 weeks going forward, with interim assessments of safety and efficacy planned every 90 days.1,2 Benetic anticipates an announcement of interim results sometime around the midpoint of 2024. The study is taking place alongside a separate OPMD natural history study conducted by Benitec, participants of which will be eligible to enroll in the clinical trial for BB-301 once baseline data regarding their condition has been collected for 6 months. Both the natural history study and the clinical trial will measure swallowing safety, swallowing efficiency, and functional performance of the pharyngeal constrictor muscles in quantitative radiographic swallowing studies. For the clinical trial, however, the primary end point will be safety of BB-301. Benetic stated that 19 patients are currently participating in the natural history study at a center in the United States and that all of them will be eligible to roll over into the clinical trial.

“We are grateful to have the opportunity to begin the clinical evaluation of BB-301 and encouraged by the research and development progress made to date,” Jerel A. Banks, MD, PhD, the executive chairman and chief executive officer of Benitec, said in a statement.1 “We are deeply appreciative of the unwavering dedication of the clinical research team at our US clinical trial site, our clinical and scientific research advisors in France, and our specialist speech language pathology research advisors in Canada, all of whom have guided the evolution of our understanding of the natural history of OPMD and our implementation of the ideal processes and procedures to facilitate the conduct of the initial clinical evaluation of BB-301. Today we have taken a critical step towards the clinical validation of our Silence and Replace-based approach to the management of genetically defined disorders, and our central goals remain focused on the improvement of the lives of patients suffering from OPMD.”

The investigational new drug (IND) application for the single-arm, open-label dose-escalation clinical trial was originally cleared by the FDA in June 2023.2,3 Benetic also intends to clinically evaluate BB-301 in Canada, pending approval of an OPMD natural history study trial package it has submitted to the country’s Research Ethics Board.

Key Takeaways

  • Benitec Biopharma has initiated its phase 1b/2a clinical trial for BB-301, an adeno-associated virus (AAV) vector-based gene therapy for oculopharyngeal muscular dystrophy (OPMD)-related dysphagia, with the first patient dosed.
  • The trial, complemented by a concurrent OPMD natural history study, will assess BB-301's safety and efficacy by measuring swallowing safety, efficiency, and functional performance of the pharyngeal constrictor muscles.
  • Benitec plans to extend the clinical evaluation of BB-301 to Canada, pending approval of an OPMD natural history study trial package it has submitted to the country’s Research Ethics Board.

“With the receipt of FDA clearance for the BB-301 IND application this year and the pace of enrollment into the OPMD Natural History Study continuing to exceed our expectations, we are well positioned to begin the evaluation of BB-301 in subjects diagnosed with OPMD,” Banks previously said in a November 15, 2023, statement.2 “The Principal Investigator and the clinical team at the US clinical trial site are finalizing the plan to dose the first study subject with BB-301 in December 2023 or January 2024. The strong interest from members of the Oculopharyngeal Muscular Dystrophy community, and the exceptional clinical trial execution by the U.S. clinical trial site, will support the generation of robust safety and efficacy data for BB-301 over the coming months.”

BB-301 is based on the company’s DNA-directed RNA interference (ddRNAi) platform and consists of a bifunctional construct that expresses a codon-optimized copy of the Poly-A Binding Protein Nuclear-1 gene (PABPN1) and 2 small inhibitory RNAs (siRNAs) that are modeled into microRNA backbones with the intention of silencing expression of mutant PABPN1; it is delivered via a novel AAV9 vector.3 In addition to the potential benefits of providing a functional copy of PABPN1, Benitec Biopharma expects that BB-301 will improve atrophy and muscle weakness by reducing the build-up of insoluble mutant PABPN1.

REFERENCES
1. Benitec Biopharma announces first subject dosed in phase 1b/2a clinical trial for gene therapy candidate BB-301 for the treatment of oculopharyngeal muscular dystrophy. News release. Benitec Biopharma Inc. November 30, 2023. Accessed December 5, 2023. https://ir.benitec.com/news-events/press-releases/detail/109/benitec-biopharma-announces-first-subject-dosed-in-phase
2. Benitec Biopharma Releases First Quarter 2024 Financial Results and Provides Operational Update. News release. Benitec Biopharma Inc. November 13, 2023. Accessed December 5, 2023. https://ir.benitec.com/news-events/press-releases/detail/107/benitec-biopharma-releases-first-quarter-2024-financial
3. Benitec Biopharma receives FDA clearance of the IND for BB-301 for the treatment of oculopharyngeal muscular dystrophy. News release. Benitec Biopharma Inc. June 26, 2023. Accessed June 28, 2023. https://ir.benitec.com/news-events/press-releases/detail/102/benitec-biopharma-receives-fda-clearance-of-the-ind-for
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