It has been less than two years since Cytokinetics’ previous ALS muscle drug, tirasemtiv, failed to meet its endpoint in a Phase III trial to treat ALS. (That was after tirasemtiv failed its Phase II trial.)
Now, according to an article in BioSpace, Cytokinetics’ new ALS drug, reldesemtiv, did not reach either of its two stated endpoints in a Phase II trial.
As expected, Cytokinetics’ stock fell on the announcement. However, the company managed to reverse the trend the same day with a favorable slant on trial results.
The company initially confirmed the drug’s shortcomings but went on to explain its reasons for believing that the drug warrants more studies.
Reldesemtiv’s spokesperson reported that the new drug is more effective than its predecessor in treating ALS patients who are coping with progressive wasting away of muscles. This is due, he explains, to its higher potency and improved permeability.
About Amyotrophic Lateral Sclerosis (ALS)
ALS is a neurodegenerative disease that affects the brain’s nerve cells (neurons). Messages are transmitted from the spinal cord and brain to voluntary muscles (muscles that can be controlled e.g legs and arms).
Patients initially present with difficulty walking, writing and speaking. This is followed by loss of strength and failure of chest muscles. There is very little that can be done to remedy the resulting respiratory failure and prolong his or her life. Additional information about ALS may be found here.
Phase II Clinical Trial FORTITUDE-ALS
Enrollment for the reldesemtiv trial totaled 458 patients with ALS. One arm received a placebo. The other three groups were assigned to one of three different dose strengths (150 mg, 300 mg, and 450 mg) two times a day for a period of twelve weeks. Details of the Trial are available here.
The Spin
The researchers pooled the three arms that involved reldsemtiv. This method of analysis showed that the patients’ primary respiratory function method only declined by twenty-seven percent.
The investigators claimed that although this still did not present a “statistical significance”, it did present a meaningful outcome clinically.
The lead investigator maintained that if the twenty-seven percent reduction could be verified, that would be considered to be clinically significant. It has been shown that after the 12 week period, the difference between the placebo group and the three reldesemtiv arms grows substantially over time.
However, an analyst at Cantor Fitzgerald financial services wrote that unless he sees plans for a trial that tests a longer dosing period, addresses safety concerns and includes other design improvements, his company may consider investing elsewhere.
The after-study analysis presented by Cytokinetics to bolster its stock had no effect on disgruntled investors.
Did Reldesemtiv Fail?
One of the trial results stated that “early termination” and serious adverse events occurred across all trial arms.
The Phase II trial investigators said one of the setbacks for reldesemtiv was the absence of any improvement in slow vital capacity (a measure of respiratory function) over a 12 week period of dosing. The study also uncovered safety issues.
It must be noted that separately, reldesemtiv dose levels failed to show a statistically significant effect over the placebo.
Yet reldesemtiv has been studied in five phase 1 trials for safety and tolerability as well as its effect on the body. Reldesemtiv’s performance in studies of spinal muscular atrophy demonstrated increases in skeletal muscle power as well as stamina and endurance.
Where There is a Need – There is Hope
Astellas Pharma is a co-developer of reldsemtiv along with Cytokinetics. The two companies are also working together to test reldsemtiv for spinal muscular atrophy.
Cytokinetics is taking aim at ALS, a neurodegenerative disorder that is difficult to treat. The company is struggling to make headway in a market that has very few therapeutic options.
It is estimated that about 20,000 people in the U.S. may have ALS at any given time. Therefore, a well-designed Phase III trial of reldsemtiv may eventually bring relief to thousands of ALS patients.
