Intravenous Trehalose Improves Dysphagia and Muscle Function in Oculopharyngeal Muscular Dystrophy (OPMD): Preliminary Results of 24 Weeks Open Label Phase 2 Trial (S28.004)

Objective: To assess the safety and efficacy of weekly IV administration of Cabaletta (trehalose 9[percnt] solution) in OPMD after a 24 week open label phase 2 trial. Background: Trehalose showed efficacy in reducing PABPN1 muscle aggregation and improving muscle function in a transgenic OPMD mouse model. Methods:25 genetically-confirmed OPMD patients received weekly infusion of 300 cc Cabaletta. Swallowing, muscle power and functional tests, and swallowing quality of life report (SWAL-QOL) were assessed at baseline and after 24 weeks. Results: No serious drug-related adverse effects were noted. Time to swallow 80cc cold water (an OPMD validated dysphagia test) improved by 35.3[percnt] (p<0.0001). This was correlated with improvement in patient reported symptom severity (p=0.05). Validated swallowing related patient questionnaire (SWAL-QOL) score improved progressively from 54.0 points to 58.8 after 12 weeks to 61.4 after 24 weeks (12.1[percnt] improvement p=0.0448). Muscle strength measured in Kg by a hand-held dynamometer showed an increased power in all 5 tested muscle actions, and reached significance for knee and foot extension. When a lower limb composite (combining hip flexion, knee extension, foot dorsiflexion) power was calculated the percent increase in strength was 13.4[percnt] (p=0.0059). Arm lift test improved by 17.6[percnt] (p=0.019), while the improvement in sit-to-stand (14.1[percnt]) and 4-stairs climb tests showed an improvement trend which did not reach significance. Conclusions: Preliminary findings show that IV trehalose is safe and improves swallowing and muscle power that are major disabilities in OPMD. The objective measured improvement in drinking time is matched by the QOL reports. This is the first time in OPMD that a pharmacotherapy shows early improvement of multiple recorded end points. A phase 3 placebo controlled study is soon to be launched. Disclosure: Dr. Argov has received personal compensation for activities with Bioblast Pharma as Chief Medical Officer. Dr. Gliko-Kabir has received personal compensation for activities with Bioblast Pharma. Dr. Brais has nothing to disclose. Dr. Yossi Caraco has received research support from BioBlast Pharma and Ultragenyx Pharmaceutical. Dr. Megiddo holds stock and/or stock options in Bioblast Pharma.