Biohaven’s SMA Phase III Trial Falls Short, Plans for Obesity Testing on the Horizon
Biohaven disclosed on Monday that its investigational myostatin and activin receptor blocker, taldefgrobep alfa, has not shown a significant improvement in motor function among spinal muscular atrophy (SMA) patients when compared to a placebo. Nonetheless, the firm maintains its optimism regarding taldefgrobep alfa and intends to consult the FDA for potential pathways forward, as stated in their release.
William Blair analysts expressed a need for clarity on future developments in SMA and anticipate insights following intended regulatory discussions to gauge the overall potential for this treatment. Due to prevailing uncertainties, the firm lowered its probability of success from 45% to 10%.
Spinal muscular atrophy is a rare genetic neurodegenerative disorder impacting roughly 1 in 10,000 births globally, primarily affecting infants and characterized by the progressive loss of motor neurons. Those with SMA face severe muscle weakness and loss of voluntary movement, often leading to fatal outcomes.
The data released from the Phase III RESILIENT SMA study indicated that taldefgrobep alfa did not lead to significant advancements in the Motor Function Measurement-32 (MFM-32) scale after 48 weeks in contrast to participants receiving placebo along with standard care.
Following the announcement of these results, Biohaven’s shares fell by 5% on Monday morning.
Despite the setback in efficacy, Biohaven maintained a positive outlook, highlighting that patients receiving the investigational treatment experienced “clinically meaningful improvements” in MFM-32 scores. They pointed to “efficacy signals” observed in specific biomarker-defined subgroups of patients.
Notably, Biohaven indicated that Caucasian patients, who represented 87% of the enrollment, experienced a statistically significant 2.2-point enhancement in MFM-32 scores at 48 weeks, achieving a p-value of less than 0.039.
Conversely, the 26 non-Caucasian participants exhibited a “higher than expected” response to the placebo, attributed by Biohaven to various factors, such as “common genetic polymorphisms in non-Caucasian individuals.”
In addition to its SMA efforts, Biohaven also revealed plans to advance its Phase II program for taldefgrobep alfa in treating obesity. This initiative is driven by data from the RESILIENT SMA study indicating that patients receiving the treatment experienced a significant reduction in body fat mass compared to those given a placebo along with standard care. Additionally, taldefgrobep alfa treatment exhibited “numerically larger” gains in lean muscle mass and bone density.
Biohaven aims to kick off a Phase II placebo-controlled trial for taldefgrobep alfa in obesity by year-end.
The William Blair analysts noted, “We view the obesity program as a distinctive strategy that may provide differentiation from existing obesity treatments and are optimistic about the observed enhancements in body composition.”