Efmitermant alfa

ACE-083 was the company’s lead product candidate for its neuromuscular therapeutic program. Cambridge, Massachusetts-based Acceleron Pharma announced that its Phase II clinical trial of ACE-083 in patients with Charcot-Marie-Tooth disease (CMT) failed to show functional improvement. The company indicated the drug did show a statistically significant increase in mean total muscle volume, which was the primary endpoint of the trial, but it didn’t lead to statistically significant improvements in function or quality of life secondary endpoints. Acceleron says it is discontinuing development of the drug. CMT is one of the most common inherited neurological disorders. It is made up of a group of disorders that affect peripheral nerves, which is to say, those outside the brain and spinal cord. It affects motor and sensory nerves and includes weakness of the foot and lower leg muscles. There are often foot deformities, such as high arches and hammertoes because of weakness of the small muscles in the feet. It affects about one in 2,500 people in the U.S. ACE-083 was the company’s lead product candidate for its neuromuscular therapeutic program. It is designed to bind to and inhibit specific proteins in the TGF-beta protein superfamily that reduce muscle growth, such as activins and myostatins (GDF8). “Unfortunately, over the course of multiple clinical trials, our myostatin-plus hypothesis has not resulted in the functional outcomes necessary to provide clinically meaningful benefits for patients with neuromuscular diseases,” said Habib Dable, president and chief executive officer of Acceleron. “We wish to thank all the patients, families, caregivers, and investigators for their support and participation in this research. I also want to acknowledge our team’s hard work and commitment to executing robust Phase II trials that have provided us the data necessary to make the difficult but informed investment decision to discontinue the program.” The company plans to refocus its resources on hematology with its Reblozyl in anemia and on pulmonary with sotatercept in pulmonary arterial hypertension (PAH). The Phase II trial evaluated ACE-083 in CMT patients who had muscle weakness in the tibialis anterior (TA), a muscle in the lower leg involved in raising the foot at the ankle. Part 1 of the trial was an open-label, dose-escalation study. ACE-083 was dosed by injection into the TA muscle once every three weeks in 18 patients to determine the safety and increases in muscle volume over a three-month period. Part 2 was a randomized, double-blind, placebo-controlled study that leveraged the optimal dose level chosen in Part 1. A total of 44 patients were involved in the trial in Part 2, receiving either ACE-083 or placebo. They were evaluated for changes in muscle volume, fat fraction, strength, function, quality of life, and safety over a six-month period, followed by a six-month open-label treatment period. In November 2019, the company’s Reblozyl (luspatercept-aamt) was the first and only erythroid maturation agent approved by the FDA to treat anemia in adults with beta-thalassemia who require regular red blood cell transfusions. At the company’s fourth quarter and full year 2019 report on February 27, 2020, Dable said, “While our hematology program remains a top priority, we are equally excited by the progress we are making in pulmonary disease. We recently announced positive topline results from the PULSAR Phase II trial of sotatercept for the treatment of PAH. These data introduce the possibility that sotatercept could potentially change the way physicians treat patients with PAH.” hbspt.forms.create({ portalId: "4413123", formId: "c4dda430-e2b0-4083-86f3-ccce0c1d4479" });

Acceleron Pharma said the Phase II FSHD trial assessing the efficacy of ACE-083 did not achieve functional secondary endpoints during the study. Shares of Acceleron Pharma have dipped in premarket trading after the Cambridge, Mass.-based company announced it was killing its development of an experimental drug in patients with facioscapulohumeral muscular dystrophy (FSHD). This morning, Acceleron Pharma said the Phase II FSHD trial assessing the efficacy of ACE-083 did not achieve functional secondary endpoints during the study. The two-part Phase II clinical trial was designed to evaluate ACE-083 in FSHD patients with muscle weakness in the biceps brachii and the tibialis anterior, a muscle in the lower leg involved in raising the foot at the ankle. While the experimental treatment did hit the primary endpoint of demonstrating a statistically significant increase in mean total muscle volume. However, the company said that the increase failed to translate to statistically significant improvements in functional tests. That failure prompted the company’s decision to terminate the study in FSHD, Acceleron said in its announcement. ACE-083 is Acceleron Pharma’s lead product candidate in its neuromuscular therapeutic program. ACE-083 is designed to bind to and inhibit select proteins in the TGF-beta protein superfamily that negatively regulate muscle growth, according to the company. ACE-083 is designed to increase strength and function in specific target muscles for improved patient function and quality of life. Acceleron said the drug was generally well-tolerated by patients. Full results of the trial will be presented at a future medical conference. Habib Dable, president and chief executive officer of Acceleron, noted the company’s disappointment in the trial’s results. He also thanked the trial participants for their time and effort. “As we have stated consistently, for ACE-083 to become an important new therapy for patients with FSHD, it would have to deliver a meaningful functional benefit on top of an ability to grow muscle. Unfortunately, in this case, the data show no evidence of such a benefit and, therefore, do not support further development of ACE-083 for FSHD,” Dable said in a statement. While the FSHD trial was halted, Acceleron is continuing to develop the drug in other indications. Dable noted that Acceleron is anticipating results from another Phase II trial involving ACE-083 in the first quarter of 2020. At that time, the company is anticipating a readout of a mid-stage trial in patients with Charcot-Marie-Tooth disease, a neuromuscular disorder of different pathophysiology than FSHD. Charcot-Marie-Tooth disease is a group of disorders that impact certain peripheral nerves, which result in muscle atrophy. Shares of Acceleron are down about 4% in premarket trading to $42.89. The stock closed at $44.65 on Monday.