First Patient Treated With Benitec Biopharma’s Oculopharyngeal Muscular Dystrophy Gene Therapy Shows Swallowing Improvements
At the 90 day timepoint, the patient showed improvements in swallowing compared to their own natural history data, as measured by videofluoroscopic swallowing studies.
The first patient treated in Benitec Biopharma’s phase 1b/2a clinical trial (NCT06185673) 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 shown improvements in swallowing at 90 days posttreatment.1
At the 90 day time point, the patient showed improvements in swallowing compared to their own natural history data, as measured by videofluoroscopic swallowing studies (VFSS), the cold water timed drinking test, and the Sydney Swallow Questionnaire (SSQ). The patient’s natural history data was gathered in a separate natural history study conducted by Benitec, which used the same measurements, from which eligible participants are able to roll over into the BB-301 trial.
On the VFSS assessments of pharyngeal area at maximum constriction to determine pharyngeal constrictor muscle function during swallowing, the patient showed an improvement at 90 days posttreatment from their natural history study average for thin liquid (5.2 units improvement, -57.1%), moderately thick liquid (5.2 units, -26.0%), extremely thick liquid (3.3 units, -15.1%), and solid food (7.1 units, 39.4%). An improvement in average pharyngeal residue postswallow was also observed, with reductions at 90 days posttreatment compared to their natural history study average for thin liquid (4.0 units improvement, -81.6%), moderately thick liquid (7.2 units, -39.6%), extremely thick liquid (9.6 units, -44.7%), and solid food (6.7 units, 35.3%). On the SSQ the patient showed an improvement of 201 points (-17.7%) at 90 days posttreatment compared to their average SSQ score from the natural history study. On the cold water timed drinking test, the patient also showed an improvement of 4.0 seconds (-13.3%) at the 90 days posttreatment timepoint compared to their natural history study average. Benitec pointed out that the patient showed improvements on many assessments at the 90 day posttreatment time point compared to the data from their first visit for the natural history study, 12 months prior to the aforementioned posttreatment assessment.
“To date, no clinical studies have systematically demonstrated a clinical improvement in OPMD patients across both objective and subjective measures of swallowing,” Jerel A. Banks, MD, PhD, the executive chairman and CEO of Benitec Biopharma, said in a statement.1 “We are, therefore, pleased to report positive interim clinical data from multiple radiographic measures as well as subject-reported outcome measures from the first subject treated with BB-301. We are highly encouraged by these early clinical trial results and for the hope that they may offer to patients and caregivers, and we look forward to reporting additional results and continuing to treat patients as they enter the dosing portion of the study from the Natural History observational lead-in period.”
Safety data from the first treated patient was reported alongside data from the second patient treated in the trial. Benitec noted that neither patient has experienced any serious adverse events, but both patients had transient cases of grade 2 gastroesophageal reflux disease (GERD). These 2 cases were each resolved after a course of commonly prescribed GERD medications.
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 In December 2023, the company announced that the first patient had been dosed.4 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.2,3
