The reldesemtiv trial, also known as FORTITUDE-ALS, was launched in the fall of 2017. The phase 2, placebo controlled study, enrolled 458 people with ALS from the US and Canada. Participants were randomized equally into 4 groups and received either 150mg, 300mg or 450mg of treatment, or a placebo orally twice per day for a period of 12 weeks.
At the 71st Annual American Academy of Neurology (AAN), Principal investigator, Jeremy Shefner, stated that the FORTITUDE-ALS trial failed to meet all of its endpoints—change from baseline in Slow Vital Capacity (SCV), change in ALSFRS-R, and change in muscle strength as measured by hand held dynamometry (HHD). However, when participants in the active treatment groups were combined, further analysis showed that they declined less than those on placebo as measured by SVC, ALSFRS-R, and HHD. The investigators also expressed that the placebo group declined slower than they expected, declining at only 6.5% in contrast to the expected 8% which may have impacted the ability to achieve statistical significance.
The news follows an earlier setback for Cytokinetics when in 2017, their lead candidate, tirasemtiv, failed to meet clinical endpoints in a pivotal phase 3 study. Over 740 participants were enrolled in that trial, with only 565 completing an open enrollment phase. There were many reports of dizziness as side effect of the treatment. The data suggested the failure of tirasemtiv to reach its primary endpoints was not due to its mechanism of action but due to tolerability issues at high doses.
Both tirasemtiv and reldesemtiv are fast skeletal muscle troponin activators (FSTAs). FSTAs are small molecules designed to slow the release of calcium with the intent of improving muscle function and mobility. Reldesemtiv is a second generation version of the drug with higher potency and it does not cross the blood brain barrier. In contrast to tirasemtiv trials, the dropout rate due to side effects on reldesemtiv was similar across the treatment and placebo groups. You can learn more about the development of FSTAs by Cytokinetics on the Endpoints Podcast.
CEO of Cytokinetics, Robert Blum, said that the data supported moving forward with a Phase 3 trial which will likely begin in 2020. Fady Malik, Cytokinetics’ executive vice president for research and development, expressed that they will be more likely to focus on participants who were less likely to be slow progressors in a phase 3 study.
Details of a Phase 3 trial will be posted on our clinical trials database. To keep up to date on clinical trials across the globe, subscribe to our clinical trials mailing list.