- A drug designed to treat amyotrophic lateral sclerosis (ALS) failed to improve respiratory function in patients with the neurodegenerative disease, sending shares in the treatment's developer, Cytokinetics Inc., tumbling down by 30% Tuesday morning.
- Cytokinetics will end development of the drug candidate, called tirasemtiv, after its Phase 3 VITALITY-ALS study failed to meet its primary or any secondary endpoints. Results also showed more patients discontinued treatment with tirasemtiv than placebo due to non-serious tolerability issues related to the drug.
- "While we believe that VITALITY-ALS demonstrated pharmacologic activity for the mechanism of action, we also believe that limitations of tirasemtiv may be addressed with our next-generation fast skeletal muscle activator, CK-2127107," said company CEO Robert Blum in a Nov. 21 statement.
Cytokinetics trial failure is another setback for ALS drug development, which has produced few treatments for the neurodegenerative condition best known as Lou Gehrig's disease.
Tirasemtiv had previously missed the mark in a Phase 2b study, but Cytokinetics saw promise in testing the drug's impact on respiratory function. Now that effort, too, has come up short.
In VITALITY-ALS, tirasemtiv failed to meet its primary endpoint measuring change from baseline in slow vital capacity at 24 weeks, nor did it hit any secondary endpoints assessed at 48 weeks. Cytokinetics did report that larger differences between drug and placebo were observed in patients randomized to the mid- and high-dose groups who could tolerate the drug — yet those differences were also not statistically significant.
More patients on tirasemtiv discontinued treatment due to "non-serious adverse events related to tolerability," likely a transitory lightheadedness that Cytokinetics had previously seen in study of the drug.
Cytokinetics will now turn to CK-2127107, a fast skeletal muscle troponin activator more commonly referred to as CK-107.
While functioning similarly to tirasemtiv, CK-107 was designed with a different chemical structure that Cytokinetics believes will render the drug more potent and more tolerable. Importantly, Cytokinetics engineered CK-107 so it would not cross the blood-brain barrier, potentially avoiding the lightheadedness that some patients experience while taking tirasemtiv.
"This is potentially three to five years behind tirasemtiv, but it could open the door on to many other patient populations that could benefit from this mechanism," Blum said in an interview with BioPharma Dive at the end of October.
At the time, Blum pointed to CK-107 as a pivot point for the company to expand beyond just ALS and take aim at other syndromes associated with muscle weakness. "That is where our strategy as a company goes from ALS and other diseases of severe neuromuscular dysfunction in the near term to a goal to develop both skeletal and cardiac muscle activators for an aging population," Blum said.
Cytokinetics, together with its Japanese partner Astellas Pharma, Inc, have three Phase 2 studies of CK-107 currently underway in ALS, spinal muscular atrophy and chronic obstructive pulmonary disease.
Cytokinetics also will keep pushing forward with development of omecamtiv mecarbil, a heart drug that the biotech has been working on with Amgen, Inc. for over a decade. Past clinical setbacks have dimmed prospects for the treatment, but success in an ongoing Phase 3 cardiovascular outcomes study could change that picture.