Gene Therapy BB-301 Improves Swallowing in OPMD Patients in Early Trial

A gene therapy being developed by Benitec Biopharma for oculopharyngeal muscular dystrophy (OPMD) has improved patients' ability to swallow, according to interim clinical trial results presented at the American Society of Gene and Cell Therapy's annual meeting.

OPMD is a rare, progressive genetic disorder in which patients experience loss of function in their head and neck muscles, leading to weakened eyelids and difficulty swallowing. Inability to fully swallow makes patients susceptible to choking and aspiration pneumonia, which can be fatal. OPMD is caused by a trinucleotide repeat mutation in the PABPN1 gene, and it has no approved therapies.

"Normal and healthy individuals swallow up to 400 times an hour, so difficulty with that particular physiological process can be extraordinarily disruptive," the CEO said during his presentation. "These patients are constantly at risk for aspiration."

Hayward, California-based Benitec is developing an AAV9-based gene therapy called BB-301 to bolster muscle mass and function by silencing and replacing the affected PABPN1 gene. The therapy includes three genes, two of which act to silence the disease-causing mutant gene, while the third delivers a wildtype version of the PABPN1 gene — a so-called silence-and-replace strategy. The therapy is administered by injection directly into the throat muscles.

The firm is evaluating the safety and preliminary efficacy of BB-301 in a Phase Ib/II clinical trial (NCT06185673) that will involve about 30 patients with genetically diagnosed heterozygous OPMD at a single U.S. site. Patients in the trial must first take part in a 26-week natural history study, in which investigators evaluate patients' symptoms using the Sydney Swallow Questionnaire and X-ray-based or video fluoroscopic swallowing studies. Following the natural history study, the Phase Ib study is investigating two BB-301 dose levels and the treatment's impact on the same outcome measures.

For their analysis, investigators bundled together the different measures of swallowing ability into a single score based on feedback from physicians. A score of two out of five on this measure indicates a response to treatment.

As of the data cutoff time, four of the six patients in the low-dose cohort have completed the 12-month study and have had robust and durable responses. Three patients had a score of four and one had a score of three on the responder scale. Two other patients have recently completed the study and also responded to treatment.

Across five different measures of swallowing abilities — one patient-reported questionnaire, one test measuring how long it takes to drink a cold glass of water, and three imaging-based evaluations — patients were considered responders if they showed improvement in at least two of the five measures after one year. All four evaluated patients were responders. One individual showed meaningful improvements across three of the swallowing assessments, while the other three improved across four of five domains. Each of the four reported significant improvements in the self-reported Sydney Swallow Questionnaire.

One patient in the low-dose cohort has now reached two years of follow-up and has exhibited durable benefit from BB-301 treatment. At year two, as compared to year one and prior to treatment, this patient's symptoms have continued to improve. This patient had a 30 percent improvement in throat closure one year after receiving BB-301, which was maintained at year two. The patient can also better clear food and liquid from their throats.

One patient has recently been dosed in the second, high-dose cohort. At three months post-BB-301 treatment, this patient has had "impressive" symptom improvement and has reached a responder score of three. As compared to a matched patient from the low-dose group, this high-dose cohort patient has more dramatic relative improvements across symptom categories. A second patient in the high-dose cohort has also been treated.

BB-301 appeared to be well tolerated with no treatment-related serious adverse events.

Benitec expects to formalize its plan for a pivotal BB-301 trial with the U.S. Food and Drug Administration in mid-2026. The company anticipates it will provide updated interim clinical study results for both cohort one and cohort two patients in the second half of 2026. Benitec added that it is well-capitalized to fund the advancement of BB-301 through completion of a pivotal study, having about $184.8 million in cash as of March 31.