TOPAZ Trial Results on Muscle Therapy Likely by June, Scholar Rock Says

Efficacy and safety results from the TOPAZ Phase 2 trial evaluating apitegromab, a  muscle-directed therapy for spinal muscular atrophy (SMA) being developed by Scholar Rock, are expected by June, the company announced.

“2020 was a transformative year for Scholar Rock with … positive interim data from the TOPAZ trial providing initial proof-of-concept of apitegromab’s potential in SMA,” Tony Kingsley, president and CEO of Scholar Rock, said in a press release.

“In 2021, we will further elucidate the potential of our product candidates through [top-line] data from our TOPAZ Phase 2 trial in SMA,” Kingsley added.

Apitegromab (previously known as SRK-015) is an investigational monoclonal antibody and a highly selective inhibitor of myostatin, a growth factor mainly produced in skeletal muscle cells (those involved in movement) to suppress muscle growth. Because muscle tissue is weak and atrophied in SMA patients, a plausible approach to increasing muscle mass is by blocking myostatin activity.

By binding to the inactive, or latent, form of myostatin, apitegromab is expected to cause fewer side effects than conventional myostatin suppressors, while still working to improve patients’ muscle strength and motor function.

The ongoing proof-of-concept trial (NCT03921528) is an open-label safety and effectiveness study of apitegromab in 58 children and young adults, ages 2 to 21, with later-onset SMA.

As of Jan. 8, one patient had left the trial for reasons unrelated to the treatment, while 56 patients have completed the 12-month study and opted to continue treatment in its extension period, Scholar Rock reported.

Participants were enrolled at multiple sites across the U.S. and Europe, and divided into three groups, according to their disease subtype and ability to walk, and age at enrollment.

Depending on the group, participants received a high or low dose of the medication (20 or 2 mg/kg) given as intravenous (into-the-vein) injections every four weeks, for up to one year.

Group one includes 23 patients (mean age, 12.6) with SMA type 3 who are able to walk. Patients in this group received apitegromab’s higher dose either alone or in combination with Spinraza, developed and marketed by Biogen.

Group two includes 15 children (mean age, 11.7) with type 2 or 3 SMA who are unable to walk unaided. Patients in this group were treated with apitegromab’s at higher dose plus Spinraza.

The 20 children in group three (mean age of about 4) have type 2 SMA. These children were randomly assigned to receive either the therapy’s high or low dose in addition to Spinraza, initiated before they were 5 years old.

Interim data released in October 2020, demonstrated apitegromab’s potential to improve motor function in patients with type 2 and 3 SMA.

Apitegromab has received orphan drug designation in the U.S. and Europe, and given rare pediatric disease status in the U.S.; all support and advance its development.