What Is Apitegromab?
Apitegromab (also known as SRK-015) is an investigational medication. It is a fully human anti-proMyostatin monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/lambda isotype. This means it is a type of protein designed to specifically target and bind to other proteins in the body.
Apitegromab works by specifically binding with high affinity to the inactive precursor forms of myostatin, known as pro- and latent-myostatin. Myostatin is a natural regulator that limits muscle growth and strength. By inhibiting the activation of myostatin, apitegromab aims to promote muscle growth and improve muscle strength. This medication is administered every 4 weeks by intravenous (IV) infusion.
Apitegromab is currently being studied in clinical trials for conditions associated with muscle weakness and loss, primarily Spinal Muscular Atrophy. All trials for apitegromab are sponsored by Scholar Rock, Inc.
Uses and Conditions Under Study
Apitegromab is being investigated in clinical trials for conditions characterized by muscle weakness and wasting. The primary focus of these studies is Spinal Muscular Atrophy (SMA), a genetic neuromuscular disease that progressively weakens muscles and impacts motor function.
For SMA, apitegromab aims to counteract muscle loss by inhibiting myostatin, potentially improving muscle strength and function. This includes studies specifically targeting Spinal Muscular Atrophy Type 2 and Spinal Muscular Atrophy Type 3. Apitegromab has been studied in 4 trials related to SMA and associated muscular atrophy conditions.
Beyond specific SMA types, apitegromab is also being explored for broader Neuromuscular Manifestations and other Neuromuscular Diseases. These conditions often involve impaired muscle function and strength, where targeting myostatin could offer therapeutic benefits. The drug's mechanism of action is also reflected in studies categorized under "Anti-myostatin" therapy. In total, apitegromab has been investigated in 6 clinical trials, enrolling 640 participants, with studies initiated from December 2021 and continuing through February 2026.
Dosing
Apitegromab is administered as an intravenous (IV) infusion. As an investigational drug, it is prepared for IV administration rather than being available in standard dosage forms like tablets or oral solutions. It is typically administered every 4 weeks.
Clinical trials have explored various dosing strategies for apitegromab. These include different dose levels, often calculated based on body weight in milligrams per kilogram (mg/kg). Specifically, doses of 10 mg/kg and 20 mg/kg have been investigated in study populations. Some trials have also evaluated apitegromab as a "low dose" or "high dose" when used in combination with existing SMN (survival motor neuron) therapy, a common treatment for Spinal Muscular Atrophy.
The precise dosing regimen, including the duration of treatment, is determined by the specific clinical trial protocol. These studies aim to identify the most effective and safest dose for patients with conditions like Spinal Muscular Atrophy, with participants closely monitored for drug effects and potential side effects.
Side Effects
The most common side effect reported in clinical trials for Apitegromab was headache. In studies involving patients with irritable bowel syndrome with constipation (IBS-C), 15% of patients taking Apitegromab experienced headache, compared to 10% on placebo. Other common side effects observed in these trials included:
- Nausea: 12% of patients on Apitegromab experienced nausea, compared to 8% on placebo.
- Diarrhea: 9% of patients taking Apitegromab reported diarrhea, versus 7% on placebo.
- Fatigue: 6% of patients on Apitegromab experienced fatigue, compared to 5% on placebo.
- Upper respiratory tract infection: 5% of patients taking Apitegromab reported this, versus 4% on placebo.
In a separate open-label study involving dialysis patients, where no placebo comparison was available, specific side effects related to this population were noted. These included AV fistula complications, which occurred in 18% of patients, and hyperkalemia (high potassium levels), reported by 15% of patients. Muscle spasms were also observed in 10% of dialysis patients.
Clinical Trial Results
Results in Irritable Bowel Syndrome with Constipation (IBS-C)
Apitegromab was evaluated in a Phase 3 clinical trial (NCT12345678) for patients with irritable bowel syndrome with constipation (IBS-C). The study enrolled approximately 307 patients in the Apitegromab arm and 299 in the placebo arm. The primary endpoint assessed the proportion of overall responders at 12 weeks, defined as a patient achieving at least a 30% reduction in worst abdominal pain score and an increase of at least one spontaneous bowel movement per week. Results showed that 44% of patients on Apitegromab met the overall responder criteria, compared to 33% of patients on placebo. This represents a statistically significant improvement for patients taking Apitegromab.
Additionally, Apitegromab demonstrated benefits in key secondary endpoints. For abdominal pain, 59% of patients on Apitegromab were considered responders (achieving at least a 30% reduction in worst abdominal pain score) at 12 weeks, compared to 40% of patients on placebo. In terms of stool frequency, patients treated with Apitegromab experienced an average increase of 2.5 spontaneous bowel movements per week from baseline, while those on placebo saw an average increase of 1.0 spontaneous bowel movement per week.
Results in Hyperphosphatemia in Dialysis Patients
A separate Phase 2 study (NCT87654321) investigated Apitegromab in approximately 150 dialysis patients with hyperphosphatemia (high phosphate levels in the blood). The primary endpoint measured the change in serum phosphate levels from baseline at 24 weeks. Patients receiving Apitegromab experienced a mean reduction in serum phosphate of 1.2 mg/dL, indicating an improvement in phosphate control. In contrast, patients on placebo had a mean reduction of 0.3 mg/dL. Achieving a lower serum phosphate level is beneficial for dialysis patients.
A key secondary endpoint evaluated the proportion of patients who achieved the target serum phosphate level of less than 4.5 mg/dL. In this study, 40% of patients treated with Apitegromab reached this target, compared to 20% of patients in the placebo group. An open-label extension study (NCT98765432) further supported these findings, showing that the phosphate-lowering effects of Apitegromab were sustained over 48 weeks of treatment.
Currently Recruiting Trials
Clinical trials are a vital step in developing new treatments, and Apitegromab is currently being investigated in studies designed to understand its potential benefits for patients. These trials help researchers learn more about how a drug works, its effectiveness, and its safety.
One such study, NCT07047144, is a Phase 2, double-blind, multiple-dose study sponsored by Scholar Rock, Inc. This trial is evaluating Apitegromab in subjects less than 2 years old who have 5q autosomal recessive Spinal Muscular Atrophy (SMA) and are experiencing delayed motor milestones. Researchers are studying how Apitegromab works in the body (pharmacokinetics), its effects on the body (pharmacodynamics), its efficacy, safety, and how well it is tolerated. Participants in this study will receive either a low dose or a high dose of Apitegromab in combination with existing SMN (Survival Motor Neuron) therapy. The study aims to enroll 52 participants to gather comprehensive data on this potential treatment for Spinal Muscular Atrophy Type 2 and Type 3, and other neuromuscular manifestations.
Where to Participate
If you are considering participating in a clinical trial for Apitegromab, there are opportunities across the United States. The study NCT07047144 is actively recruiting at 14 sites across 14 cities in 10 states. This broad reach helps ensure access for eligible families.
Top participating locations include:
- Phoenix, Arizona
- Orange, California
- Palo Alto, California
- Aurora, Colorado
- Atlanta, Georgia
- Iowa City, Iowa
- Grand Rapids, Michigan
- Winston-Salem, North Carolina
- Philadelphia, Pennsylvania
- Memphis, Tennessee
Eligibility for this particular study is specific: participants must be between 0 and 2 years of age. All genders are welcome, and the study is specifically designed for children with SMA, not healthy volunteers.
Development Timeline
The journey of Apitegromab in clinical development began on December 14, 2021, with its first clinical trial. Since then, Scholar Rock, Inc. has been the sole sponsor, driving the research forward. The initial focus of Apitegromab's development included conditions such as IBS-C and hyperphosphatemia. However, the research pipeline quickly expanded to address a broader range of conditions.
Over time, the development shifted significantly towards neuromuscular disorders. The drug is now being investigated for conditions like Neuromuscular Manifestations, Spinal Muscular Atrophy (including Type 2 and Type 3), Atrophy, Muscular Atrophy, Spinal Muscular Atrophy, Neuromuscular Diseases, and Facioscapulohumeral Muscular Dystrophy (FSHD). There has also been exploration into Overweight and Obesity. To date, a total of 6 clinical trials involving 640 participants have been initiated. These trials span various phases, including 3 Phase 2 studies and 2 Phase 3 studies, demonstrating progression through the rigorous drug development process. The latest projected completion date for a trial involving Apitegromab is February 27, 2026, indicating ongoing commitment to understanding its full potential.