Cytokinetics’ new muscle activator compound, CK-2127107, shows promising safety, tolerability, and effectiveness in three early clinical trials in healthy volunteers. The data supports the ongoing Phase 2 trial of the drug in patients with spinal muscular atrophy (SMA).
The article, “CK-2127107 Amplifies Skeletal Muscle Response to Nerve Activation in Humans,” published in the journal Muscle & Nerve, presented findings from all three Phase 1 trials.
“These published results reinforce CK-2127107 as a promising drug candidate with potential advantages relative to tirasemtiv that may include tolerability and potency,” Fady I. Malik, MD, PhD, Cytokinetics’ executive vice president of Research & Development, said in a press release.
CK-2127107 is an investigational next-generation fast skeletal muscle troponin activator (FSTA) which Cytokinetics develops in collaboration with Astellas Pharma. The compound aims to act as a muscle activator by slowing calcium signaling in so-called fast skeletal muscle fibers.
CK-2127107 was explored in three separate Phase 1 trials, adding to data from two earlier studies.
In the first study, called CY 5011, 35 healthy male volunteers received two ascending doses of the drug and one placebo dose — one dose per treatment period. The study showed that doses up to 4,000 mg were well tolerated, with no dose-limiting side effects detected.
The second study, CY 5012, tested multiple ascending doses in 59 male and female volunteers. The study enrolled both younger — ages 18-55 — and older people. Researchers came to the conclusion that the drug was processed in a similar way in older and younger people.
In the third trial, CY 5013, researchers tested muscle strength after a single dose of CK-2127107 in 16 male volunteers. Participants were tested four times, receiving 300 mg, 1,000 mg, and 3,000 mg single doses in a random order, or a placebo once a week before researchers tested their muscle activation.
The study showed that CK-2127107 triggered a muscle force more than double of that seen with tirasemtiv. The study measured muscle contractions after nerve stimulation, and also concluded that the best effect was seen when a motor neuron was stimulated in a fashion similar to the natural signaling frequency of motor neurons.
All three trials also concluded that the drug was relatively well tolerated — all adverse events were mild or moderate. Laboratory values, neurological examinations, vital signs, brain waves, walk tests, and blood oxygen levels were all normal after the treatment.
Researchers also concluded that higher doses gave rise to higher blood concentrations of the drug — a desirable feature of any new drug.
CK-2127107 is currently being assessed in a Phase 2 trial in patients with SMA types 2–4 (NCT02644668). The trial is still recruiting participants in the U.S. and Canada. Interested patients can find more information, including contact details, at the trial’s registration page.
CK-2127107 is intended for the treatment of patients with muscle fatigue or weakness. In addition to SMA, the compound is being tested in Phase 2 trials in patients with amyotrophic lateral sclerosis (ALS), elderly people with mobility limitations, and patients with chronic obstructive pulmonary disease (COPD)
The trials are expected to be completed by next year.
The company has dropped the development of tirasemtiv after an ALS trial failed to show effectiveness.