Acceleron announces 'positive' preliminary results from Part 1 of ACE-083 trial
Acceleron Pharma announced positive preliminary results for the first two cohorts in Part 1 of the Phase 2 clinical trial with ACE-083 in patients with facioscapulohumeral dystrophy, a rare genetic muscle disorder that results in progressive focal muscle loss and weakness. The company plans to initiate Part 2 of the ACE-083 FSHD Phase 2 trial during 2Q18. Part 1 of the Phase 2 trial is an open-label, dose-escalation study of ACE-083 designed to evaluate safety as well as changes in total muscle volume in up to 36 patients with FSHD. Preliminary results include data from 23 patients evaluable for magnetic resonance imaging among two different cohorts. Each patient received ACE-083 as a unilateral intramuscular injection once every three weeks for 12 weeks. Total muscle volume changes were measured by MRI relative to baseline at 3 weeks after the last injection of ACE-083. Based on overlap in dosing on a milligram per gram muscle analysis, dose cohorts were pooled for the analyses of each muscle. The tibialis anterior, which is located in the lower leg, is the main muscle responsible for ankle dorsiflexion, or the ability to lift the front of the foot when taking a step. Over 70% of FSHD patients experience tibialis anterior weakness over the course of their disease, which can lead to general decreased mobility and an increased frequency of falling. The TA cohorts generated a mean total muscle volume increase of 12.6%. The TA cohorts produced a mean decrease or improvement in muscle fat fraction of 5.3%. The biceps brachii, which is located in the upper arm, is a major muscle responsible for elbow flexion, or the ability to lift the lower arm. A majority of FSHD patients experience biceps brachii weakness early in their disease, which leads to the inability to lift objects or perform other important daily activities without assistance. The BB cohorts generated a mean total muscle volume increase of 13.2%. The BB cohorts produced a mean decrease or improvement in muscle fat fraction of 0.6%. In the BB cohorts, the majority of patients had less intramuscular fat at baseline relative to the patients in the TA cohorts. Patients with higher fat fraction in the BB cohorts at baseline demonstrated larger decreases in fat fraction with treatment. Strength and function tests are being explored in Part 1 to assist with the design of the randomized, double-blind, placebo-controlled Part 2 of the study. Given the lack of placebo control and small sample size of patients in Part 1, no conclusions can be made on the strength and function assessments at this time. Effects of ACE-083 on strength and function versus a placebo-control will be evaluated in Part 2 of the study. There were no serious adverse events reported. The most common adverse events were injection site related and grades 1-2. One patient experienced a related grade 3 non-serious adverse event of lower leg intramuscular swelling. This patient fully recovered and was discontinued from the study.