Silence and Replace Gene Therapy Cleared for Oculopharyngeal Muscular Dystrophy Clinical Trial


Benitec Biopharma is planning to initiate a phase 1b/2a clinical trial to evaluate BB-301.

Benitec Biopharma has received FDA clearance for its investigational new drug (IND) application for BB-301, an investigational adeno-associated virus (AAV) vector-based silence and replace gene therapy intended to treat oculopharyngeal muscular dystrophy (OPMD)-related dysphagia.1

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. Benitec Biopharma is planning to initiate a phase 1b/2a clinical trial to evaluate BB-301. The clinical trial will enroll patients from a natural history study of patients with OPMD that is currently being conducted by the company. The natural history study currently has 13 patients participating, all of whom will be eligible to rollover to the clinical trial after they have reached 6 months under evaluation. The natural history study is assessing swallowing safety, swallowing efficiency, and functional performance of pharyngeal muscles via quantitative radiographic swallowing measurements. The clinical trial will assess the same measurements in participants. Benitec Biopharma expects to report interim clinical data from the trial about every 90 days after each participant receives treatment with BB-301.

“The FDA’s clearance of our IND for BB-301 is a significant milestone for OPMD patients and for Benitec as a company,” Jerel A. Banks, MD, PhD, the executive chairman and CEO of Benitec Biopharma, said in a statement.1 “The clearance of BB-301 for clinical use represents the first potential treatment for these frequently debilitating and possibly fatal symptoms of OPMD.”

Approximately 15,000 people in the United States, Canada, Western Europe, and Israel have OPMD. Symptoms of the disorder include inability to swallow liquids and solids, chronic malnutrition, chronic choking, regurgitation, aspiration, eyelid drooping, proximal limb weakness, and potentially fatal aspiration pneumonia.1,2 Currently, the standard of care for OPMD consists of palliative treatment; there are no disease-modifying therapies available. 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.

In addition to the United States, Benitec Biopharma also intends to evaluate BB-301 at clinical trial sites in Canada and France.3 In a May 15, 2023, operational update the company stated that it had submitted a natural history study trial package to Canada’s Research Ethics Board. It also anticipates clearance of a clinical trial application (CTA) for the phase 1b/2a clinical trial in Canada in the second half of 2023. Benitec Biopharma additionally noted that it expects to complete filing of a CTA for the clinical trial in France in the third quarter of 2023.

“We remain focused on opening additional clinical study sites in Canada and France, pending ongoing discussions with Institutional Review Boards and regional regulators,” Banks said in the operational update.3

Substantial progress in the realm of gene therapy for muscular dystrophy was recently made with the FDA’s approval of Sarepta Therapeutics’ delandistrogene moxeparvovec (SRP-9001) for the treatment of Duchenne muscular dystrophy on June 22, 2023.4 SRP-9001 is indicated for ambulatory pediatric patients aged 4 through 5 years who have a confirmed mutation in the DMD gene, excepting those who have a deletion in exon 8 and/or exon 9. SRP-9001 will be marketed under the name Elevidys.

1. 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.
2. Areas of Research. Benitec Biopharma Inc. Website. Accessed June 28, 2023.
3. Benitec Biopharma releases third quarter 2023 financial results and provides operational update. News release. Benitec Biopharma Inc. May 15, 2023. Accessed June 28, 2023.
4. Sarepta Therapeutics Announces FDA Approval of ELEVIDYS, the First Gene Therapy to Treat Duchenne Muscular Dystrophy. News release. Sarepta Therapeutics. June 22, 2023. Accessed June 28, 2023.
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