Biohaven’s Myostatin Inhibitor Falls Short in Phase 3 Trial for Spinal Muscular Atrophy
This week, Biohaven released news regarding the phase 3 trial outcomes of taldefgrobep alfa, a recombinant protein designed to target myostatin. Regrettably, the trial did not meet its primary endpoint in individuals diagnosed with spinal muscular atrophy (SMA).
SMA is a rare neurodegenerative condition that leads to the degeneration of motor neurons and subsequent muscle atrophy. It stems from mutations in the SMN1 gene and is categorized into five types based on severity and age of onset, with most cases presenting symptoms during early childhood.
Currently, multiple therapies exist for SMA, including gene therapy Zolgensma and the antisense oligonucleotide therapy (ASO) Spinraza. Nonetheless, these treatments primarily alleviate neurological symptoms rather than addressing the muscle wasting associated with the disorder.
The approach of inhibiting myostatin to enhance muscle function in conditions like SMA has recently garnered interest. Myostatin naturally limits muscle growth, and its inhibition allows muscles to develop larger and stronger than they typically would, potentially benefiting individuals experiencing muscle weakness.
In the context of SMA, there have been encouraging developments, including a positive phase 3 outcome from Scholar Rock regarding its myostatin inhibitor earlier this year.
Biohaven’s RESILIENT SMA study evaluated taldefgrobep in conjunction with the standard SMA care against a placebo group receiving the same standard care, in a sample of just over 200 patients. While some improvement in motor function was observed in the treatment group, it did not surpass the improvements noted in the placebo cohort.
The company noted that participants of Caucasian descent and those with measurable myostatin at enrollment showed better motor function outcomes than their counterparts.
“SMA is a devastating rare disease and although we are disappointed that taldefgrobep did not achieve a statistically significant difference in the broad study population… we are encouraged that a majority subgroup did show a treatment benefit compared to the placebo arm,” commented Cliff Bechtold, Taldefgrobep Development Lead and President of Biohaven Ireland, in an official statement.
He further added, “The observed treatment effect on motor function, which had a similar magnitude on the Motor Function Measurement-32 scale after 1 year of treatment as approved therapies (i.e., risdiplam), along with the strong biomarker evidence of target engagement, suggests that taldefgrobep may play a potentially beneficial role in a majority subgroup population of SMA patients.”
Investigation of a Secondary Indication
Despite disappointing results for taldefgrobep concerning SMA, the company is also investigating the drug for obesity treatment. This development phase is still early (phase 1/2), but Biohaven indicates that findings from the SMA trial lend support for this additional indication.
In this trial, those treated with taldefgrobep exhibited a notable decrease in total fat mass alongside increases in lean muscle mass and bone density compared to the placebo group at the study’s conclusion.
The metabolic outcomes linked to taldefgrobep might offer it a competitive advantage over other anti-obesity medications such as GLP-1 receptor analogs like Novo Nordisk’s Wegovy (semaglutide) and Eli Lilly’s Zepbound (tirzepatide), which, although effective for weight loss, often result in loss of both fat and muscle mass.
The market for obesity treatments is undoubtedly competitive, especially considering both Roche and Eli Lilly are assessing anti-obesity options aimed at muscle preservation, and Scholar Rock is also testing its SMA candidate in obesity contexts. The future competitiveness of Biohaven in this area remains to be determined.