6-month Analysis of SMA Patients in TOPAZ Trial Delayed to Year’s End

A planned six-month interim analysis of a Phase 2 study of SRK-015 in children and adults with spinal muscular atrophy (SMA) will be delayed by about three months due to the COVID-19 pandemic, with early data now expected by year’s end, Scholar Rock announced.

The TOPAZ clinical trial (NCT03921528) completed patient enrollment in January, and most (72%) patients finished their six-month visit as of May 1, but others were either unable to receive their doses or be assessed on time, the company said in a press release.

“We are humbled by the tenacity and commitment of the patients and clinicians with whom we have the privilege to work as we continue to adjust to the challenges of the COVID-19 pandemic,” Nagesh Mahanthappa, PhD, president and CEO of Scholar Rock, said in the release.

SRK-015 is an investigational antibody designed to improve muscle strength and motor function by blocking an inactive form of the myostatin protein. Myostatin is primarily found in skeletal muscle cells (those involved in movement), and works in concert with other growth factors and hormones to prevent muscle growth.

By binding to the inactive, or latent, form of myostatin, SRK-015 is designed to prevent its conversion into the active form. This could increase muscle mass, countering the symptoms of SMA. SRK-015 is also believed to be safer than other approaches targeting active myostatin, which also block other closely related factors.

After showing promise in animal models, and being found safe and well-tolerated by healthy volunteers in a Phase 1 clinical trial, SRK-015 advanced to testing across a range of SMA patients in the TOPAZ study.

A total of 58 people with later-onset disease, ages 2 to 21, were divided into three groups according to their disease subtype and ability to walk. All would be treated by intravenous infusion every four weeks for one year.

Group 1 is composed of 23 patients, ages 5 or older, with SMA type 3 who are able to walk, some of whom are using an approved SMA treatment. Group 2 includes 15 SMA type 2 or 3 patients, also at least age 5 at enrollment, who are unable to walk but able to sit independently. Group 3 has 20 patients with SMA type 2, enrolled at age 2 or older.

TOPEZ’s main goal is to determine improvements in motor function from treatment initiation to the study’s end.

Preliminary data on the 29 patients who completed a first treatment cycle found that SRK-015 increased the levels of inactive myostatin by up to 100 times, suggesting the antibody is effectively binding to its target and preventing its conversion into active myostatin. No new safety signs were reported.

To date, one group 1 patient left the study SRK-015 for reasons unrelated to the treatment or the pandemic. Most patients (70%) were enrolled in the U.S., and others across Italy, Spain, and the Netherlands.

Fifty-one of the 57 patients have completed their five-month visit, and 41 have been assessed for safety and efficacy at six months. The company is working closely with clinical sites to minimize delays among those whose six-month visit was affected by the outbreak.

Once these visits are completed, Scholar Rock is planning to release the interim analysis covering SRK-015’s safety and efficacy, as well as data on its pharmacokinetics — how the therapy behaves in the body — and pharmacodynamics — how the body is affected by the treatment.

“It is with a primary focus on the safety and well-being of our patients, clinical investigators and employees, that we are committed to continuing the execution of the SRK-015 TOPAZ Phase 2 [trial],” Mahanthappa said. “Though we may continue to experience uncertainty during these unprecedented times, Scholar Rock is planning for additional updates [this program] later this year.”

Top-line data from TOPAZ will also be delayed, with a likely release during the first half of 2021, Scholar Rock announced.