FDA approves Phase 1b/2a clinical trial of BB-301 for OPMD
The oculopharyngeal muscular dystrophy treatment aids with swallowing
The U.S. Food and Drug Administration (FDA) has cleared Benitec Biopharma to start a Phase 1b/2a clinical trial of the investigational gene therapy BB-301 for swallowing difficulties associated with oculopharyngeal muscular dystrophy (OPMD).
Dosing is expected to start later this year, following the rollover of participants in the ongoing natural history study conducted by the company. A natural history study is one that tracks disease progression in the absence of treatment. Thirteen patients are currently enrolled in the natural history study.
Preliminary safety and efficacy data are expected approximately every 90 days following the dosing of each patient.
Trial participants rolling over from the natural history study will first undergo six months of data collection. Dosing of BB-301 will take one day, and then each patient will be assessed for the same imaging and clinical outcome measures used in the natural history study. This includes the evaluation of swallowing safety and efficiency, as well as the function of the pharyngeal muscles.
“The FDA’s clearance of our [investigational new drug application] for BB-301 is a significant milestone for OPMD patients and for Benitec as a Company. The clearance of BB-301 for clinical use represents the first potential treatment for these frequently debilitating and possibly fatal symptoms of OPMD,” Jerel A. Banks, MD, PhD, executive chairman and CEO of Benitec, said in a company press release.
Mutations in PABPN1 gene
OPMD is caused by mutations in the PABPN1 gene, resulting in the production of an abnormal PABPN1 protein. The protein will clump inside muscle cells and impair their function, leading to muscle weakness.
Symptoms usually appear after age 40. Typical manifestations include droopy eyelids and difficulty swallowing, leading to malnutrition and aspiration pneumonia (when food or liquid gets into the airways or lungs).
BB-301 uses an adeno-associated virus as a carrier to deliver DNA-directed RNA interference technology, which combines suppressing the production of mutant PABPN1 while providing a healthy copy to make a normal protein.
“We believe BB-301’s silence and replace strategy is uniquely positioned for the treatment of OPMD by halting mutant expression while providing a functional replacement protein,” the company stated in the press release.
BB-301 has been granted orphan drug designation in the U.S. and the European Union.
Preclinical studies in mouse models showed BB-301 reduced the production of abnormal PABPN1, reduced protein clumps, increased production of the healthy protein, and improved muscle strength, according to the company.
A study in beagles demonstrated BB-301 can be delivered efficiently via injection into muscles at specific sites in the pharynx (the upper part of the throat, just behind the mouth) using an open surgical procedure.