Muscle-directed Therapy Apitegromab Put on FDA’s Fast Track

Apitegromab, Scholar Rock’s muscle-directed therapy for spinal muscular atrophy (SMA), was granted a fast track designation by the U.S. Food and Drug Administration.

“We are delighted to receive Fast Track designation and look forward to working closely with the FDA towards our aim of establishing apitegromab as the potential first muscle-directed therapy for patients with SMA,” Tony Kingsley, company president and CEO, said in a press release.

Fast track designation is intended to accelerate a therapy’s development and expedite its approval by providing more frequent meetings with the FDA and discussions about the development plan.

The therapy had been previously named an orphan drug in the U.S. and Europe, as well as given rare pediatric disease status in the U.S. and priority medicines (PRIME) designation in Europe. All are meant to speed its development and regulatory review.

“Recent Fast Track and PRIME designations granted by the regulatory agencies underscore the continuing unmet medical needs of patients with SMA,” said Yung Chyung, MD, chief medical officer of Scholar Rock.

The investigational therapy works by preventing the conversion of the latent form of myostatin, a protein mainly produced by skeletal muscle and that suppresses muscle growth, into its active form.

Through this mechanism of action, apitegromab is thought to boost patients’ muscle mass and strength, with fewer side effects than conventional suppressors of myostatin’s active form.

Top-line data from the ongoing proof-of-concept Phase 2 TOPAZ trial (NCT03921528) showed that apitegromab was safe, and improved or stabilized motor function in children and young adults with SMA types 2 and 3 (later-onset disease) over one year. The trial is evaluating the therapy’s safety and effectiveness in 58 patients, ages 2 to 21.

Participants, allocated to one of three groups, received intravenous (into-the-vein) infusions of apitegromab either at a low (2 mg/kg) or a high (20 mg/kg) dose once every four weeks for up to one year.

Most received the therapy’s high dose (83%) and were also being treated with Spinraza (81%) — the first approved SMA disease-modifying therapy.

The trial’s main aim is to assess changes in motor function using the revised Hammersmith scale in ambulatory patients (those able to walk independently), and with the Hammersmith functional motor scale expanded in non-ambulatory patients.

Higher scores indicate greater motor function, and increases of at least three points in Hammersmith scores are typically considered clinically meaningful.

Six-month data showed that most patients achieved stable or improved motor function. About a third (35%) reached clinically meaningful motor function improvements, as shown by an increase of at least three points in Hammersmith scores.

The improvements were more pronounced and more common among younger type 2 children (59%; ages 2–6) than in older type 2 and 3 patients (22%–31%; ages 7–21).

“The majority of non-ambulatory patients in our TOPAZ trial experienced increases in Hammersmith scores, highlighting the therapeutic potential of apitegromab to address motor function impairments in this patient population,” said Chyung.

Based on these findings, Scholar Rock plans to launch a Phase 3 clinical trial to test apitegromab in a larger patient population.

“We believe the recently announced top-line data from the TOPAZ Phase 2 trial showed the transformative potential of apitegromab for patients with SMA,” Kingsley added.