Date: 2015-06-19
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the 19th International SMA (Spinal Muscular Atrophy) Researcher Meeting held during the 2015 Annual SMA Conference
Company: Cytokinetics (USA - CA)
Product: CK-2127107
Action
mechanism: skeletal muscle activator. Skeletal muscle contractility is driven by the sarcomere, the fundamental unit of skeletal muscle contraction. It is a highly ordered cytoskeletal structure composed of several key proteins. Skeletal muscle myosin is the cytoskeletal motor protein that converts chemical energy into mechanical force through its interaction with actin. A set of regulatory proteins, which includes tropomyosin and several types of troponin, make the actin-myosin interaction dependent on changes in intracellular calcium levels. CK-2127107, a novel skeletal muscle activator arising from Cytokinetics\' skeletal muscle contractility program, slows the rate of calcium release from the regulatory troponin complex of fast skeletal muscle fibers, which sensitizes the sarcomere to calcium, leading to an increase in skeletal muscle contractility. CK-2127107 has demonstrated pharmacological activity that may lead to new therapeutic options for diseases associated with muscle weakness and fatigue. In non-clinical models of Spinal Muscular Atrophy, a skeletal muscle activator has demonstrated increases in skeletal submaximal muscle force in response to neuronal input and delays in the onset and reductions in the degree of muscle fatigue. CK-2127107 has been the subject of five completed Phase I clinical trials in healthy volunteers, which evaluated safety, tolerability, bioavailability, pharmacokinetics and pharmacodynamics.
Disease:
Therapeutic area: Neuromuscular diseases - Rare diseases
Country:
Trial details:
Latest
news: * On June 19, 2015, Cytokinetics announced that results from three double-blind, randomized, placebo-controlled Phase I studies of CK-2127107 in healthy volunteers were presented in a poster at the 19th International SMA (Spinal Muscular Atrophy) Researcher Meeting held during the 2015 Annual SMA Conference at the Westin Crown Center in Kansas City, MO. In a pharmacodynamic study that was designed to assess the translation of the mechanism of CK-2127107 to humans, treatment with the fast skeletal muscle activator increased muscle force produced by the tibialis anterior muscle in response to nerve stimulation. Cytokinetics is developing CK-2127107 in collaboration with Astellas Pharma. The poster titled, \"Pharmacokinetics and Pharmacodynamics of the Selective Fast Skeletal Muscle Troponin Activator, CK-2127107,\" was presented by Andrew Wolff, MD, FACC, Cytokinetics\' Chief Medical Officer, and included data from Phase I studies that evaluated the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic effects of CK-2127107 in healthy volunteers. In these studies, CK-2127107 was well-tolerated at single doses up to 4000 mg and the PK profile of CK-2127107 was linear and dose-proportional across the range of doses studied. Data from the Phase I studies also showed significant dose-, concentration-, and frequency-dependent increases in the force of muscle contraction elicited by nerve stimulation in healthy volunteers. The increases in force were most evident in the mid-range of nerve stimulation frequency, consistent with preclinical studies. By directly increasing skeletal muscle function, CK-2127107 may enhance physical performance in patients with neuromuscular diseases including SMA. These data support further evaluation of CK-2127107 and its potential to effect measures of muscle performance and function.
