There seems to be some good news on the horizon for individuals with Charcot-Marie-Tooth (CMT) disease. Acceleron Pharma announced positive preliminary results from Part 1 of the Phase 2 clinical trial with ACE-083 in patients with CMT disease at the Peripheral Nerve Society (PNS) annual meeting held in Baltimore, Maryland. CMT is one of the most common inherited neurological diseases and is associated with significant focal muscle weakness. The Company plans to initiate Part 2 of the ACE-083 CMT Phase 2 trial in the third quarter of 2018.
“Preliminary Phase 2 results of ACE-083 in patients with CMT show robust mean increases in total and contractile muscle volume, reductions in fat fraction, and an encouraging safety profile,” said Robert K Zeldin, M.D., Chief Medical Officer of Acceleron. “We now look forward to initiating the randomized, placebo-controlled portion of the Phase 2 trial in which we will evaluate ACE-083’s potential to improve function over a six-month treatment period.”
Part 1 of the trial was an open-label, dose-escalation study that enrolled a total of 18 patients (in three cohorts of six patients each) with CMT1 or CMTX who received ACE-083 at dose levels of 150 mg, 200 mg, or 240 mg. ACE-083 was administered by injection into the tibialis anterior (TA) muscle bilaterally once every three weeks for three months to evaluate safety and increases in muscle volume. The TA, which is located in the lower leg, is the primary muscle responsible for ankle dorsiflexion, or the ability to lift the front of the foot when taking a step. TA weakness can result in foot drop and increased risk of falls.
CMT is one of the most common inherited neurologic diseases. It is estimated to affect more than 125,000 people in the United States. The primary clinical manifestations of CMT include muscle weakness in the lower legs and arms. The lower leg muscle weakness can result in foot drop leading to a high-stepped gait and frequent tripping or falls. The disease is typically diagnosed by the presence of a characteristic pattern of muscle weakness, nerve conduction studies, and genetic testing. There are no FDA-approved drug therapies for CMT.
Muscle volume was measured by magnetic resonance imaging (MRI) three weeks after the last injection of ACE-083. Muscle volume and fat fraction are represented as the changes from baseline averaged for each side.
- Mean total muscle volume (TMV) increases ranged from 12.6% to 14.2%.
- Mean absolute decreases (improvement) in fat fraction ranged from 1.7% to 3.5%.
In addition, treatment with ACE-083 resulted in mean increases from baseline in contractile muscle volume (an MRI-derived calculation to measure viable, functional muscle volume as part of the TMV), ranging from 15.8% to 19.6%.
The most common adverse events—injection-site reactions, muscle spasms, and myalgia—were mild or moderate (grades 1-2).
“There are currently no FDA-approved therapies for patients with CMT with muscle weakness. The muscle volume and fat fraction changes demonstrated in Part 1 of the ACE-083 trial are encouraging,” said Florian P. Thomas, M.D., neurologist and principal investigator at Hackensack Meridian School of Medicine at Seton Hall University. “We’re hopeful that ACE-083 may become an important option for patients.”
