Cytokinetics' comeback attempt with second-gen muscle drug is slammed by a PhII failure in ALS
Seventeen months after Cytokinetics’ lead muscle drug crashed and burned in a Phase III ALS trial, their $CYTK second-gen attempt has now gone down to defeat in a Phase II trial.
This new drug, reldesemtiv, has been billed by CEO Robert Blum as a “more potent, more penetrable” drug for treating muscle wasting in patients. While their drug tirasemtiv struggled and failed in treating ALS patients because of the necessarily dose-limiting aspects of the therapy, he said, reldesemtiv would be free to punch in a higher weight class.
It didn’t work.
In a Phase II trial reported out on Sunday, investigators said their study failed on change from baseline in slow vital capacity (SVC) after 12 weeks of dosing (p=0.11). The analysis also shows poor p values for ALSFRS-R and slope of the Muscle Strength Mega-Score.
The biotech’s shares dropped about 20% in early trading Monday. But the company managed to turn that around, ending the day in the green after making its case for the drug.
The South San Francisco-based biotech’s release on Sunday acknowledges the failure up front, then goes on to list the reasons why the company nevertheless believes the data are actually quite good, justifying more trial work.
Their case rests on a post hoc analysis, which tend to be ignored by investors unhappy with a setback like this. According to the researchers, the data reflect “clinically meaningful magnitudes of effect” across all dose levels. They also maintain that the placebo group declined at a slower rate than expected, which didn’t help.
“Results from FORTITUDE-ALS are among the most impressive we have seen in a Phase II clinical trial in ALS,” boasted lead investigator Jeremy Shefner. “Especially noteworthy are the consistency and durability of effects observed across treatment arms on clinically meaningful endpoints.”
This isn’t the first time Cytokinetics — partnered with Astellas — has touted weak or failed data. Last summer Blum scoffed at my questions about reldesemtiv’s failure to remain clinically significant at week 8 after hitting the mark at week 4.
“That’s within the noise of statistics this size,” he said. “We don’t see that as a tapering.”
Almost exactly 5 years ago tirasemtiv also failed a Phase IIb trial for ALS, but it didn’t stop the biotech from insisting that the drug warranted a Phase III.
Cytokinetics’ shares closed Friday at $8.85, around the same level it’s been treading water at since the Phase III disaster.