Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as SRK-015
Apitegromab · 6 trials · 13 indications
Incidence of TEAEs and SAEs by severity
The HFMSE assesses the physical abilities of patients with Type 2 and Type 3 SMA. It comprises of 33 items graded on a scale of 0, 1, or 2, where 0 denotes unable, 1 denotes performed with modification or adaptation, and 2 denotes performed without modification or adaptation. The overall score is the sum of the scores for all activities with a maximum achievable score of 66. Higher scores indicate increased motor function.
Percent change from baseline in total lean muscle volume (LMV) as measured by full body magnetic resonance imaging (MRI) at week 52
Apitegromab concentrations in serum
Total latent myostatin concentrations in serum
Change from baseline in the raw score of the Bayley Scale of Infant and Toddler Development, Fourth Edition - Gross Motor Subscale (BSID-4 GMS) at 48 weeks. BSID-4 GMS is a standardized assessment commonly used to evaluate development across 5 domains in infants and young children. It consists of 58 items, scored from 0 to 2 for each item, with higher scores indicating better gross motor development.
Dual-energy X-ray absorptiometry was used to evaluate body composition
The Revised Hammersmith Scale (RHS) is a 36 item clinical assessment of physical abilities in patients with Type 2 SMA and ambulatory or nonambulatory patients with Type 3 SMA. For the ambulatory Type 3 patients 5-21 years of age in Cohort 1 (N=23), the primary endpoint was the change from baseline in RHS total score at month 12. The RHS has a minimum achievable score of 0 and a maximum achievable score of 69. The RHS includes 33 items that are graded on a scale of 0, 1, 2, where 0 denotes the lowest level and 2 denotes the highest level of ability/function. The remaining 3 items are scored 0 or 1, where 0 denotes an inability and 1 denotes an ability to achieve. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement.
Cohort 2: For the nonambulatory Type 2 and Type 3 patients 5-21 years of age in Cohort 2 (N=15), the primary efficacy endpoint was the change from baseline in HFMSE total score at month 12. Cohort 3: For the nonambulatory Type 2 patients ≥2 years of age in Cohort 3 (N=20), the primary efficacy endpoint was the change from baseline in HFMSE total score at month 12. The Hammersmith Functional Motor Scale Expanded (HFMSE) assesses the physical abilities of patients with Type 2 and Type 3 SMA comprises 33 items graded on a scale of 0, 1, or 2, where 0 denotes unable, 1 denotes performed with modification or adaptation, and 2 denotes performed without modification or adaptation.
| Arm | Type | Description |
|---|---|---|
| Treatment Period | EXPERIMENTAL | Patients who are ≥2 years of age with Type 2 and Type 3 SMA will receive apitegromab 20 mg/kg every 4 weeks by intravenous (IV) infusion during the 104-week Treatment Period |
| Main Efficacy Population (Apitegromab 10 mg/kg) | EXPERIMENTAL | Aged 2-12 years at Screening. Participants were randomized to receive apitegromab 10 mg/kg for up to 52 weeks. |
| Main Efficacy Population (Apitegromab 20 mg/kg) | EXPERIMENTAL | Aged 2-12 years at Screening. Participants were randomized to receive apitegromab 20 mg/kg for up to 52 weeks. |
| Main Efficacy Population (Placebo) | PLACEBO_COMPARATOR | Aged 2-12 years at Screening. Participants were randomized to receive placebo for up to 52 weeks. |
| Exploratory Subpopulation (Apitegromab) | EXPERIMENTAL | Aged 13-21 years at Screening. Participants were randomized to receive apitegromab 20 mg/kg for up to 52 weeks. |
| Exploratory Subpopulation (Placebo) | PLACEBO_COMPARATOR | Aged 13-21 years at Screening. Participants were randomized to receive placebo for up to 52 weeks. |
| Apitegromab | EXPERIMENTAL | 10 mg/kg IV |
| Placebo | PLACEBO_COMPARATOR | Placebo IV |
| Apitegromab low dose + SMN Therapy | EXPERIMENTAL | Patients who are less than 2 years of age with SMA will receive apitegromab every 4 weeks by intravenous (IV) infusion during the 48-week Treatment Period. Patients must have been treated with an approved SMN1-targeted therapy (ie, onasemnogene abeparvovec-xioi) or are continuing to be treated with an approved SMN2-targeted therapy (ie, nusinersen or risdiplam). |
| Apitegromab high dose + SMN Therapy | EXPERIMENTAL | Patients who are less than 2 years of age with SMA will receive apitegromab every 4 weeks by intravenous (IV) infusion during the 48-week Treatment Period. Patients must have been treated with an approved SMN1-targeted therapy (ie, onasemnogene abeparvovec-xioi) or are continuing to be treated with an approved SMN2-targeted therapy (ie, nusinersen or risdiplam). |
| Cohort 1 | EXPERIMENTAL | Apitegromab + incretin mimetic |
| Cohort 2 | PLACEBO_COMPARATOR | Placebo + incretin mimetic |
| Cohort 3 | EXPERIMENTAL | Type 2 SMA |
| Name | Type | Description |
|---|---|---|
| Apitegromab | DRUG | Apitegromab (SRK-015) is an investigational, fully human immunoglobulin G4 monoclonal antibody that specifically binds to human proforms (i.e., inactive precursor forms) of myostatin, pro- and latent- myostatin, with high affinity, inhibiting activation of myostatin, a negative regulator of muscle growth and strength. |
| Placebo | DRUG | Placebo was administered every 4 weeks by intravenous (IV) infusion. |
| Nusinersen | DRUG | Nusinersen is a current standard-of-care SMN therapy that targets the SMN2 gene. It will be administered intrathecally per the prescribing information. |
| Risdiplam | DRUG | Risdiplam is a current standard-of-care SMN therapy that targets the SMN2 gene. It will be administered orally per the prescribing information. |
| Tirzepatide | DRUG | Glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist. Tirzepatide was administered every week by subcutaneous injection. |
| SRK-015 | BIOLOGICAL | SRK-015 is a fully human anti-proMyostatin monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/lambda isotype that binds to human pro/latent myostatin with high affinity. SRK-015 will be administered every 4 weeks by intravenous infusion. |
Inclusion Criteria: * Patients have completed the Phase 2 TOPAZ (Study SRK-015-002) trial or the Phase 3 SAPPHIRE (Study SRK-015-003) trial. (For TOPAZ, completed is defined as completion of Visit EC14 in Extension Period C or participating in TOPAZ at the time the trial is ended. For SAPPHIRE, com...
Top 6 of 7 competitors
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Biogen Inc. | BIIB | 13 | PHASE3 | Nusinersen, Salanersen |
| Novartis AG Sponsored ADR | NVS | 7 | PHASE3 | Onasemnogene abeparvovec |
| Biohaven Ltd. | BHVN | 1 | PHASE3 | Taldefgrobep Alfa |
| Scholar Rock Holding Corp. | SRRK | 2 | PHASE3 | Apitegromab |
| argenx SE Sponsored ADR | ARGX | 1 | PHASE2 | ARGX-119 |
| Hoffmann-La Roche | RHHBY | 2 | PHASE2 | Risdiplam, RO7204239 |
Apitegromab is an investigational monoclonal antibody being studied for spinal muscular atrophy, facioscapulohumeral muscular dystrophy, and overweight or obesity. It is not yet approved for any indication and remains in clinical development. Scholar Rock is evaluating it across these three therapeutic areas in Phase 2 and Phase 3 trials.
Apitegromab targets myostatin, also known as MSTN. It is a monoclonal antibody that acts as an inhibitor of myostatin, a protein that limits muscle growth. By blocking myostatin, apitegromab is designed to promote muscle mass and function in conditions involving muscle weakness or loss.
Apitegromab is being developed by Scholar Rock Holding Corporation, which trades on the Nasdaq under the ticker SRRK. The company is the sponsor of the clinical program evaluating apitegromab in spinal muscular atrophy, facioscapulohumeral muscular dystrophy, and overweight or obesity.
Apitegromab is in Phase 2 and Phase 3 clinical development. It is investigational and has not been approved by the FDA for any indication. The program includes a completed Phase 2 trial in overweight or obesity, recruiting Phase 2 trials in FSHD and SMA, and an active Phase 3 long-term extension trial in SMA.
Apitegromab is being studied in four registered trials. These include NCT07435129 in facioscapulohumeral muscular dystrophy, NCT07047144 in spinal muscular atrophy in children under two years old, NCT06445075 in overweight or obesity, and NCT05626855, a Phase 3 long-term safety and efficacy study in SMA.
Apitegromab has received Fast Track and Orphan Drug designations from the FDA. These designations are intended to support and expedite the development of therapies for serious conditions and rare diseases. The drug remains investigational and has not been approved for any indication.