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After a crushing PhIII failure, Cytokinetics says its next-gen muscle drug is lining up well in PhII — but big challenges loom

For the past 6 months, Cytokinetics $CYTK CEO Robert Blum has been holding things together in the wake of a devastating late-stage disaster that swept away its lead muscle drug. He takes pride in the fact that he was able to soldier on without gutting the staff. And now the biotech and its partners at Astellas are stepping forward with their follow-up drug — looking to persuade investors that they can learn from the grievous setback and make a comeback in the field of strengthening patients afflicted by a range of ailments.

It’s not going to be easy or quick. Investors took a close look at the data today and the fallout ended driving the biotech’s stock down 17%.

Robert Blum

Initially coded CK-2127107 and now called reldesemtiv — which replaces the defunct tirasemtiv — Blum touts the new contender as being a safer, better approach to amping up muscles. Tirasemtiv, he says, was done in by the fact that the drug penetrated the blood brain barrier,  causing dizziness and limiting dosing. This time around, he says, their next-gen approach won’t have that limitation.

Now in a lineup of mid-stage studies, investigators for the company rolled out the first snapshot of Phase II data for spinal muscular atrophy. And the data raise some questions, even as Blum highlights the dose effect among the 70 patients. 

Not surprisingly, the low 150 mg dose used in the study failed to generate a statistically significant result for a 6-minute walk test — one of the standard endpoints available to developers in the arena. That’s not unusual in a study like this, which goes in search of hammering out the right dose to go into a registration study. The 450 mg did get to statistical significance at 4 weeks, and then slipped below a significant response at 8 weeks.

According to researchers, the 450 mg dose of the drug increased walking distance by 35.63 meters (p= 0.0037) at week four and 24.89 meters (with a p value of 0.0584) at week eight relative to placebo. There was also a significant increase in Maximal Expiratory Pressure —which measures respiratory muscles — at the low and high dose at 8 weeks, but neither dose scored under the 0.05 mark at 4 weeks, which suggests a possible improvement over time.

I asked Blum about the 6-minute test results. Sliding efficacy over a short period like that — a shift also seen in the lower dose arm of the study — could signify that the drug has only a transient effect, which could prove a serious threat.

Blum, though, batted it back, insisting that the downward shift was due solely to the small patient population involved. Researchers have the chance to double up on that dose in a pivotal study, he adds. And future work would also extend out endpoints on efficacy to 12 weeks.

“That’s within the noise of statistics this size,” the CEO says. “We don’t see that as a tapering.”

“This is the first of four such studies,” adds the CEO. “These data lend support for the mechanism and the molecule. We know reldesemtiv is more potent, more penetrable into muscle.”

Researchers at Cytokinetics and Astellas are now focused on ALS, COPD and frailty in the elderly, though they may eventually go down the path of sarcopenia as the FDA works on new regulatory pathways for aging. This particular program, says Blum, isn’t directly competitive with the other SMA drugs in the clinic, such as the one PTC and Roche are reporting on today, or Biogen’s pioneering Spinraza. A drug like theirs can be nicely complementary to any other drugs targeted directly at the disease.

Where do they go from here? Blum isn’t talking timelines yet, as he cautiously moves forward toward finalizing another pivotal trial. Failure isn’t going to be an option.


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Director, Financial Planning and Analysis
Molecular Templates Austin, TX
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Molecular Templates Austin, TX
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Koneksa Health New York, NY

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