After trial flops in spinal muscular atrophy, depression and bipolar disorder—and a costly rare disease drug rejection—Biohaven is undergoing a reset, recasting its former SMA candidate for obesity.
Biohaven’s taldefgrobep alfa may have missed the mark for spinal muscular atrophy, failing a Phase 3 trial in November 2024, but the biologic did help patients lose weight while preserving lean muscle and bone density—a holy grail of obesity treatments. Now the company is hoping the drug will help pivot its pipeline toward the lucrative weight loss market.
“We’re a small biopharma company, and when we have good assets, we do a full vetting of that asset, and we’ll play where that asset can bring real value to patients and to the company,” Peter Ackerman, senior vice president of clinical development, told BioSpace ahead of the American Diabetes Association (ADA) annual conference this week in New Orleans.
In an interview with BioSpace in January, CEO Vlad Coric discussed his company’s plans to repurpose taldefgrobep alfa, which Biohaven acquired from Bristol Myers Squibb in 2022. Ackerman and several of his Biohaven colleagues are BMS alumni.
“We’ve been talking about obesity as an indication for taldefgrobep for many years,” Ackerman said.
Currently in a Phase 2 study for obesity, taldefgrobep is a myostatin and activin receptor blocker, according to Ackerman. Activin [ActRII] receptors reside primarily on skeletal muscle and adipose tissue, he explained. “Blocking myostatin signaling optimizes skeletal muscle growth.”
The preservation of lean muscle mass is a major challenge with GLP-1 medicines, Ackerman continued. On these drugs, 30% to 45% or more of the total weight loss is being driven by loss of lean muscle mass. “We won’t have that,” he said. “We believe that we can bring higher quality of weight loss.”
Companies like Roche and Scholar Rock have targeted the latent form of myostatin, Ackerman said, which “has no interaction with the ActRII receptor.” Taldefgrobep’s binding of this receptor is key, Ackerman said, “because it competitively inhibits other key growth factors, including . . . activin A, B, C and E,” which are important to fat storage.
“If you can shut down both the myostatin and activin signaling pathway, we believe that you can optimize lean mass growth and optimize the reduction in fat mass,” he said.
Biohaven completed enrollment in the Phase 2 proof-of-concept study—which is evaluating taldefgrobep as a once-weekly and once-monthly monotherapy—in March. The trial’s primary endpoint is change in body weight at 24 weeks, with change in total body fat, change in total body lean mass and safety as key secondary endpoints. Topline data are expected in the second half of this year.
And when it comes to taldefgrobep, Biohaven isn’t planning to stop with obesity.
“Obesity is a good first indication, because of the hardcore outcome measures, but muscle mass is very important to longevity and keeping quality of life as we all age,” Coric told BioSpace last week, adding that each decade after age 30, people lose almost 8% of their muscle mass. Therefore, he said, future indications could include healthy aging and preventing age-related muscle loss.
The regulatory pathway for obesity therapies is still very much focused on weight loss, however. Biohaven recognized this during the company’s R&D Day, held May 27.
“While Biohaven is aiming to differentiate taldefgrobep alfa as a lean-mass sparing agent for obesity, at the R&D day it acknowledged that the regulatory path forward for endpoints other than percent weight loss is unclear,” William Blair said in a note the following day.
However, the analysts added, “[m]anagement expressed confidence that taldefgrobep alfa monotherapy can demonstrate weight loss that will meet regulatory standards for approval, and that an alternative regulatory path will not be required.”
Can Biohaven bounce back?
After a challenging couple of years, Biohaven has a lot riding on these early signals of efficacy in obesity. Since before taldefgrobep’s Phase 3 fail, when the company’s share price had topped $50, the stock has fallen some 80%, selling for just over $10 apiece at the time of publication.
Indeed, taldefgrobep is not Biohaven’s only experimental asset to fail a key trial recently. In January, the company recorded a flop for its potassium channel agonist BHV-7000, or opakalim, in a Phase 2 proof-of-concept trial for major depressive disorder (MDD). BHV-7000 previously failed a Phase II/III bipolar mania trial, and the company said it would move on from the drug candidate in psychiatric disorders.
This followed an FDA rejection in November 2025 for Biohaven’s glutamate modulator troriluzole in spinocerebellar ataxia (SCA).
William Blair analysts at the time called the rejection “disappointing” and said it raises “potential liquidity ramifications.” Indeed, the FDA’s decision caused Biohaven to miss out on a $150-million tranche of funding from Oberland Capital Management, part of a larger private investment worth up to $600 million. The biotech also cut R&D spending by 60%.
Over the past year, Coric said Biohaven has “spent considerable time advocating” for troriluzole in SCA. “We stand by the data and believe this is an approvable package, and we are continuing to interact with the FDA, and we will not stop advocating for patients that this should be approved,” he added.
Overall, however, these events have sent Biohaven back to the drawing board in many respects.
“Biohaven is in a period of pipeline reprioritization and R&D cost reduction to preserve capital,” William Blair analysts wrote on May 5 following the company’s first quarter earnings report.
“In terms of clinical catalysts, the focus will be on pivotal Phase II/III data of opakalim in focal onset epilepsy (FOS) and placebo-controlled Phase II data of taldefgrobep alfa in obesity,” they added.
While opakalim struck out in MDD, with this asset too, Biohaven has another shot on goal. Pivotal topline data from a Phase 2/3 trial are due for the potassium channel agonist in epilepsy in the second half of 2026, according to the company’s 2026 key milestones chart.
Ackerman noted that while the FDA’s requirement is sustained weight loss through 48 weeks, the 24-week readout for taldefgrobep in obesity “gives us an opportunity to get an earlier read on the data and get earlier into Phase 3, if we see what we’re hoping to see.”
At ADA, Biohaven will be presenting data supporting its dosing choices for the Phase 2 trial, including the once-monthly option, which “our modeling suggests is very viable,” Ackerman said.
“If we can meet our goals of having significant reductions in fat mass and fat mass reduction on par with . . . a leading agent in the GLP-1–based therapies, we think that that is an attractive proposition for individuals.”
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