While taldefgrobep alfa failed to show improved motor function in spinal muscular atrophy, treated patients saw a marked reduction in body fat. Biohaven plans to launch a Phase II trial in obesity by the end of the year.
Biohaven on Monday announced its investigational myostatin and activin receptor blocker taldefgrobep alfa failed to significantly improve motor function in patients with spinal muscular atrophy, as compared with placebo. Still, the company remains confident in taldefgrobep alfa and “plans to engage the FDA regarding potential next steps forward” for the candidate, according to the announcement.
“We have questions on the path forward in SMA and look forward to updates from planned regulatory discussions to determine overall potential in this indication,” William Blair analysts wrote in an investor note. The firm “reduced our probability of success here from 45% to 10% given this uncertainty.”
Afflicting one in 10,000 births worldwide, spinal muscular atrophy (SMA) is a rare and genetic neurodegenerative disease that predominantly affects young children and manifests as the progressive and widespread destruction of motor neurons. Patients with SMA suffer from the loss of voluntary motion and severe muscle weakness, often leading to death.
Monday’s readout, from the Phase III RESILIENT SMA study, showed that taldefgrobep alfa did not significantly improve scores in the Motor Function Measurement-32 (MFM-32) scale at 48 weeks as compared with patients treated with placebo plus standard of care.
Biohaven is down 5% on Monday morning after the data drop.
Despite the efficacy miss, Biohaven struck an optimistic note, pointing out that patients treated with the experimental drug saw “clinically meaningful improvements” in MFM-32 scores. The biotech also zeroed in on what it called “efficacy signals” in certain biomarker-defined patient subgroups.
In particular, Biohaven noted that in Caucasian patients—who made up majority of the participants, accounting for 87% of the study’s enrollment—treatment with taldefgrobep alfa resulted in a 2.2-point improvement in MFM-32 at 48 weeks, an effect that was statistically significant with a p-value of less than 0.039.
Meanwhile, in the 26 non-Caucasian participants, the biotech flagged a “higher than expected placebo response.” There are several reasons for this, according to Biohaven, including “common genetic polymorphisms in non-Caucasian subjects.”
Beyond SMA, Biohaven on Monday also announced that it will push forward with its Phase II plans for taldefgrobep alfa in obesity. This decision was driven by findings from RESILIENT SMA showing that treated patients saw a marked significant reduction in body fat mass versus counterparts treated with placebo and standard of care. Taldefgrobep alfa treatment also resulted in “numerically larger” improvements in lean muscle mass and bone density.
Biohaven plans to initiate a Phase II placebo-controlled trial for taldefgrobep alfa in obesity by the end of the year.
“We see the obesity program as an interesting approach to potentially differentiate from current obesity treatments and are encouraged by observations of improved body composition,” the William Blair team wrote.
