Scholar Rock Reports Success in Phase 3 SMA Study, Stock Soars

Scholar Rock has announced promising results from its experimental therapy for spinal muscular atrophy (SMA), which significantly enhanced motor function over a year when compared to a placebo in a pivotal study. With this success, the 12-year-old biotech firm aims to pursue a broad label for its first potential commercial drug.

The company is working on a muscle-targeted antibody treatment named apitegromab, designed to be used alongside existing SMA therapies. These therapies, Spinraza and Evrysdi, developed by Biogen and Roche respectively, are intended to increase levels of a crucial motor neuron protein. Scholar Rock’s Phase 3 SAPPHIRE study focused on individuals with late-onset SMA who were already on these medications. The study included a primary efficacy group of patients aged 2 to 12 and an additional exploratory group of patients aged 13 to 21.

In the primary efficacy group (ages 2 to 12), those who were administered either 10 or 20 mg/kg doses of apitegromab exhibited a 1.8-point improvement in motor function on the HFMSE scale compared to the placebo group. This result yielded a p-value of 0.0192, indicating statistical significance as the study's primary endpoint was set at p<0.025.

Following the announcement, Scholar Rock’s stock ($SRRK) surged over 300% on Monday morning. Jefferies analyst Michael Yee noted that the data was unexpected and could enhance the prospects of Scholar Rock’s mid-stage study of the same antibody for obesity.

SMA is a condition that causes the degeneration of nerve cells controlling voluntary muscles, leading to muscle weakness and wasting over time. Apitegromab works by targeting specific forms of myostatin, a protein in skeletal muscles that restricts muscle growth. By inhibiting myostatin, apitegromab could potentially increase muscle mass.

Further analysis revealed that the results were not dependent on the dose. Patients receiving the 10 mg/kg dose showed a 2.2-point improvement on the motor function scale compared to placebo, whereas those receiving the higher 20 mg/kg dose demonstrated a 1.4-point difference.

Scholar Rock’s CEO, Jay Backstrom, mentioned that the FDA requested they include a 10 mg/kg dose in their study. He stated that the company did not expect a dose-dependent response between the 10 and 20 mg/kg doses due to their comparable pharmacologic effects. "In today’s drug development landscape, we seek the lowest dose that offers the best efficacy and safety. Our data strongly indicate that the 10 mg/kg dose is effective," Backstrom added.

In the exploratory age group of 13 to 21, the motor function results were described as “meaningful and consistent.” Backstrom confirmed during an investor call that the company intends to seek approval for apitegromab for a wide age range. Scholar Rock also plans to initiate a study involving children under 2 years old, emphasizing the importance of starting treatment early.

Regarding safety, the company reported no discontinuations due to adverse events.

Other companies are also exploring myostatin-targeting therapies. Roche and Biohaven are testing their experimental drugs in SMA patients, with Biohaven expected to release Phase 3 data soon. Additionally, Roche, Lilly, and Regeneron are investigating drugs that inhibit myostatin signaling in obesity.

Scholar Rock plans to submit applications to the FDA and EMA to market apitegromab within the first quarter of next year. They also aim to present detailed study results in early 2025. For their obesity program, the company anticipates mid-stage study results for apitegromab in the second quarter of the next year.