Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Apitegromab · 5 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
| 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 |
| 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. |
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...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Biogen Inc. | BIIB | 13 | PHASE3 | Nusinersen |
| Novartis AG Sponsored ADR | NVS | 5 | 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 |
| Illumina, Inc. | ILMN | 1 | - | Undisclosed |
Apitegromab is an investigational small molecule being developed for spinal muscular atrophy (SMA), facioscapulohumeral muscular dystrophy (FSHD), and overweight and obesity. It is being studied in patients with SMA types 2 and 3, including those under 2 years old, and in adults with FSHD.
Apitegromab targets myostatin (MSTN), a protein that inhibits muscle growth. As a myostatin inhibitor, it is designed to promote muscle mass and strength, which is relevant for neuromuscular conditions like SMA and FSHD.
Apitegromab is being developed by Scholar Rock Holding Corporation, a biopharmaceutical company traded on the NASDAQ under the ticker symbol SRRK. The company is conducting clinical trials in the United States and multiple European countries.
Apitegromab is in Phase 2 and Phase 3 clinical trials. It has completed a Phase 3 trial in later-onset SMA, has an active Phase 3 long-term extension study, and is currently recruiting for Phase 2 trials in infants with SMA and adults with FSHD. It is not yet FDA approved.
Apitegromab is being studied in several trials: NCT05156320, a completed Phase 3 trial in later-onset SMA; NCT05626855, an active Phase 3 long-term extension study; NCT07047144, a recruiting Phase 2 trial in children under 2 with SMA; and NCT07435129, a recruiting Phase 2 trial in FSHD.
Apitegromab is distinct from nusinersen and risdiplam, which are used in combination with it in clinical trials. While those drugs target SMN2 splicing, Apitegromab targets myostatin to support muscle function. It is being evaluated alongside these standard SMA therapies.