ACE-083 Granted FDA’s Orphan Drug Status to Treat Charcot-Marie-Tooth Disease

ACE-083 has been granted orphan drug status by the U.S. Food and Drug Administration (FDA) to treat Charcot-Marie-Tooth (CMT) disease, the therapy’s developer Acceleron Pharma announced.

The treatment is being tested in 15 U.S. states in a Phase 2 trial (NCT03124459) that is enrolling participants with CMT type 1 and CMT type X.

Orphan drug status aims to encourage therapies for rare and serious diseases through benefits such as seven years of market exclusivity and exemption from FDA application fees.

“This formal designation aligns with our mission to develop therapies for patients with rare diseases of high unmet medical need,” Robert K. Zeldin, MD, chief medical officer of Acceleron said in a press release.

Positive preliminary findings from part 1 of the Phase 2 trial evaluating the efficacy of ACE-083 have shown that the treatment improved the total and contractile muscle volume in patients, which was accompanied by a decrease in the proportion of fat in the muscles. The therapy showed a good safety profile.

Part 1 was a non-randomized, open-label, dose-escalation study in which patients received increasing doses of ACE-083. The therapy was injected once every three weeks for three months into one of the major muscles of the lower leg called the tibialis anterior.

The results were presented in a poster and oral presentation titled “Preliminary Phase 2 Results for ACE-083, Local Muscle Therapeutic in Patients with CMT1 and CMTX” at the 2018 Annual Meeting of the Peripheral Nerve Society in Baltimore, Maryland.

Part 2 of the Phase 2 trial is looking to recruit about 40 patients with CMT1 or CMTX. Patients will be randomly assigned to receive either a placebo or ACE-083 once every three weeks over a six-month, double-blind treatment, followed by an open-label treatment period of six months.

Preliminary results of the second part of the study are expected by the end of 2019.

The FDA granted fast track designation in December 2018 to ACE-083, a status that expedites its therapy review process.

“In clinical trials to date, treatment with ACE-083 has resulted in substantial increases in muscle volume in target muscles. We believe that if our ongoing studies demonstrate that such increases lead to improved functional outcomes, ACE-083 has the potential to become an important new therapy for patients with CMT,” said Zeldin.

ACE-083 is a locally-acting therapy designed to increase muscle strength and function at target muscles. It is based on the naturally-occurring protein follistatin, and works by inhibiting the proteins of the TGF-β family that reduce muscle growth. The therapy is injected directly into target muscles, thereby preventing unwanted effects in untreated muscles or other organs.

Acceleron received fast track designation for ACE-083 to treat patients with facioscapulohumeral muscular dystrophy (FSHD), a condition characterized by poor muscle function, and is currently testing ACE-083 on patients with FSHD.