Biohaven’s taldefgrobep alfa on FDA’s fast track
Biohaven Pharmaceuticals' experimental medicine also is an orphan drug
The U.S. Food and Drug Administration (FDA) has given fast track designation to Biohaven Pharmaceuticals‘ experimental medicine taldefgrobep alfa for the treatment of spinal muscular atrophy (SMA).
The designation is granted to therapies that show potential in addressing serious conditions for which available treatments fall short. It is meant to speed their clinical development and regulatory review by enabling more frequent communications with the regulatory agency.
“We are very pleased the FDA granted Fast Track designation for taldefgrobep alfa for the treatment of SMA,” Lindsey Lee Lair, MD, vice president of clinical development at Biohaven, said in a press release.
Taldefgrobep alfa also has received FDA’s orphan drug designation for the treatment of SMA, which provides benefits such as reduced regulatory fees and the potential for seven years of market exclusivity should the therapy be approved.
SMA is a genetic disease that affects motor neurons, the nerve cells responsible for voluntary muscle movement, leading to muscle weakness and wasting.
While a number of disease-modifying therapies are available for SMA, these medications cannot revert damage that already has occurred, and patients can still experience muscular symptoms that significantly affect their quality of life.
“Children and adults living with SMA experience significant muscle weakness and functional impairments affecting their quality of life daily, and a substantial unmet medical need persists,” Lair added.
Myostatin is a naturally occurring protein that normally limits muscle growth, preventing muscles from becoming too large during muscular development. Thus, blocking this protein has the potential to increase muscle mass and strength in people with SMA and other neuromuscular diseases.
Taldefgrobep alfa, also known as BHV2000, is an investigational therapy designed to block myostatin’s activity via two mechanisms: by directly lowering myostatin’s levels and by blocking its protein receptor, which stops myostatin-derived signaling in skeletal muscles.
New family of proteins
Administered via under-the-skin (subcutaneous) injections, taldefgrobep alfa is an adnectin, a new family of proteins that work similarly to antibodies but form stronger connections with their target and remain in circulation for longer periods, potentially allowing less frequent dosing.
In preclinical studies and clinical trials, inhibition of myostatin led to a significant increase in muscle mass, supporting taldefgrobep alfa as a promising treatment for SMA and other neuromuscular conditions.
According to Biohaven, the medication has the potential to further improve motor function and other clinical measures when given in combination with other approved treatments.
The company now is conducting a Phase 3 trial, called RESILIENT (NCT05337553), to investigate the impact of taldefgrobep alfa in muscle function in SMA patients receiving an approved disease-modifying therapy or who have been treated with the gene therapy Zolgensma (onasemnogene abeparvovec).
The trial is enrolling up to 225 children and adults, ages 4-21 years, who will be assigned randomly to weekly under-the-skin injections of either taldefgrobep alfa or a placebo for 48 weeks. All will then have the option to join an open-label extension part and receive the active medication for another 48 weeks.
Trial recruitment
Recruitment is underway in more than 20 locations across the U.S. and in Poland, with additional sites in the U.S. and Europe expected to open.
“We are excited about the potential for taldefgrobep alfa to improve the lives of patients and families affected by SMA,” Lair said.
“Fast Track designation from the FDA underscores the high unmet medical need in SMA and supports the need for additional novel combination therapies in children and adults living with this progressive neurologic disease,” said Karen Chen, PhD, CEO of the SMA Foundation. “We are happy to see the commitment of health authorities to rapidly advance the development of new therapies.”
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