Cytokinetics' Astellas-partnered ALS drug misses goal in phase 2

Cytokinetics added up the silver linings and concluded reldesemtiv warrants further development. (VSRao/Pixabay)

Cytokinetics’ reldesemtiv has missed the primary endpoint in a phase 2 amyotrophic lateral sclerosis (ALS) trial. The Astellas-partnered drug failed to beat placebo on a lung function test, but Cytokinetics thinks a post hoc analysis shows a path forward for the program.

Astellas paid $65 million to expand its relationship with Cytokinetics to cover ALS in 2016, picking up an option on tirasemtiv and a chance to advance fast skeletal muscle troponin activator reldesemtiv in the process. Tirasemtiv flunked a phase 3 test in 2017, but Cytokinetics continued to see potential in reldesemtiv, partly in a belief the follow-up asset is more tolerable than its predecessor. 

Cytokinetics emerged from the phase 2 reldesemtiv trial in ALS with data to support its tolerability hypothesis. But the drug nonetheless failed to beat placebo against the primary endpoint and other assessments of its efficacy. 

After 12 weeks of dosing, patients who received reldesemtiv statistically performed no better than their peers on placebo against measures of lung function, symptom severity and muscle strength. 

Even so, Cytokinetics and its collaborators talked up the findings, zeroing in on positive trends and the results of a post hoc analysis. The analysis pooled the results from all the reldesemtiv arms and compared them to placebo, resulting in a statistically significant improvement on the ALS Functional Rating Scale-R of disease symptom severity. 

Cytokinetics added up the silver linings and concluded that the drug warrants further development.  

“We are encouraged by the results of the trial as they further validate the potential of skeletal muscle activation in treating patients battling ALS,” Cytokinetics Executive Vice President Fady Malik said in a statement. “This phase 2 trial of reldesemtiv demonstrated consistency of effect for doses, endpoints and timepoints and we believe the results support progression of reldesemtiv in further clinical trials toward potential registration.”

The prospect of advancing reldesemtiv on the back of mixed phase 2 data has echoes of the tirasemtiv development program. That drug missed the primary goal of improved ALSFRS scores in a phase 2 ALS trial in 2014, only for Cytokinetics to advance it into a pivotal study on the strength of data on secondary respiratory function endpoints. The pivotal study failed.