SMA Drug by Scholar Rock Maintains Muscle in Zepbound Users During Phase 2 Trial

Scholar Rock's recent developments reveal promising potential for its investigational drug, apitegromab. While primarily aimed at treating spinal muscular atrophy (SMA), new findings suggest additional applications in the field of obesity treatment. Scholar Rock's exploration into obesity therapies comes as muscle preservation becomes a pivotal area for pharmaceutical companies targeting weight loss solutions.

The U.S. Food and Drug Administration (FDA) is currently reviewing apitegromab as a treatment for SMA, with a decision expected by September. This drug functions as an inhibitor of myostatin activation, a mechanism thought to be beneficial for patients with SMA. However, recent phase 2 study results indicate that apitegromab might also enhance weight loss quality in obesity treatments.

In a midstage clinical trial, conducted on patients battling obesity, apitegromab was evaluated in combination with tirzepatide, the active ingredient in Eli Lilly's obesity drug, Zepbound. The study revealed intriguing results: while tirzepatide alone led to a 30.2% loss of lean mass as part of the total weight reduction, incorporating 10 mg/kg of apitegromab reduced the lean mass loss to 14.6% over 24 weeks. This combination not only halved the proportion of lean mass lost but also improved the quality of weight loss.

Patients receiving the apitegromab-tirzepatide combination therapy experienced significant fat mass reduction, with 85% of their weight loss attributed to fat and only 15% to lean mass. In contrast, the tirzepatide-placebo group saw a 70% fat mass reduction and a 30% lean mass loss. Additionally, in terms of total weight reduction, patients on the combination therapy lost 12.3% of their body weight, slightly less than the 13.4% seen in the tirzepatide-placebo group.

Apitegromab was reported to be "generally well tolerated," with no serious adverse events or treatment discontinuations linked to its use. Following the release of this promising data, Scholar Rock's stock experienced a notable uptick, rising by 5% to $32.80 from $31.15.

The focus on muscle preservation is gaining traction among biopharmaceutical companies competing in the weight-loss market. For instance, companies like Roche and Regeneron have been acquiring assets to pair with their muscle drug candidates. Additionally, Eli Lilly recently entered into a partnership with Juvena Therapeutics to enhance muscle health and body composition.

Akshay Vaishnaw, M.D., Ph.D., and president of R&D at Scholar Rock, highlighted the significance of these findings. He noted that while GLP-1 therapies, such as tirzepatide, have been instrumental for individuals dealing with obesity and related disorders, they can also lead to substantial lean muscle loss, posing health risks. Vaishnaw expressed satisfaction with the results of the EMBRAZE trial, which achieved its primary endpoint, asserting that the platform of selective myostatin inhibitors showed promise in supporting healthier weight loss by preserving lean mass.

Despite this progress, Scholar Rock remains dedicated to its primary goal of launching apitegromab for SMA treatment, pending FDA approval. The approval filing for apitegromab followed a successful phase 3 trial in October 2024, which demonstrated a 1.8-point improvement in motor function for SMA patients compared to a placebo over 52 weeks.

In summary, Scholar Rock's investigational drug, apitegromab, is showing potential beyond its initial scope, offering hope for enhanced obesity treatment by maintaining muscle mass during weight loss. This discovery aligns with the broader industry trend of targeting muscle preservation to deliver more effective and healthier weight management solutions. As the company awaits the FDA's decision, the prospects of apitegromab appear promising in both the SMA and obesity spheres.