Results of an exploratory Phase 2 study evaluating the effectiveness of reldesemtiv (CK-2127107) for a first time in patients with spinal muscular atrophy (SMA) will be presented at the Cure SMA annual conference set for mid-June in Texas.
Reldesemtiv is a next-generation fast skeletal muscle troponin activator (FSTA) being developed by Cytokinetics 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.
Data from preclinical studies show that reldesemtiv improved muscle function in two mouse models of SMA, and three Phase 1 clinical trials in healthy volunteers supported the compound’s safety and tolerability, and suggested it might be effective.
The Phase 2 placebo-controlled, multiple-dose trial (NCT02644668) is investigating reldesemtiv’s effectiveness and safety in 70 ambulatory and non-ambulatory patients with SMA type 2, 3, or 4.
Its primary objective is to see if treatment can improve patients’ muscular function and respiratory capacity, and ease fatigue. Secondary goals include measures of the treatment’s safety, tolerability, and pharmacodynamics, or how the therapy is absorbed, distributed and metabolized, and then expelled.
Enrolled patients, ages 12 or older, were randomized to two groups — 39 in a lower-dose group (150 mg) and 31 in a higher-dose group (450 mg), and given oral reldesemtiv or placebo twice a day for eight weeks after an initial one-time dose on day one. The trial is due to conclude in June.
Researchers are assessing respiratory capacity, as well as motility and balance, through the six-minute walk test (6MWT) and timed-up-and-go test in ambulatory patients (those with types 3 and 4, and able to walk). In non-ambulatory participants (types 2 and 3), upper limb strength and functionality is being tested.
Preliminary data on characteristics of patients in the low-dose group (first enrolled and called group 1) were released at last year’s Cure SMA conference. The 2018 conference opens in Dallas on June 14 and runs through June 17.
“We look forward to these data in adolescents and adults with types II, III and IV SMA, a population in need of new therapies to address impaired muscle function and weakness despite the promise of gene-directed therapies,” Fady Malik, Cytokinetics’ executive vice president of research and development, said in a press release.
Reldesemtiv is also being developed as a potential treatment for people living with other disorders associated with muscle weakness and/or fatigue.
The compound was designated an orphan drug by the U.S. Food and Drug Administration (FDA) as a potential treatment for SMA in 2017.