Isembyld (apitegromab-mstn) / Scholar Rock - LARVOL DELTA

Scholar Rock Announces FDA Approval of ISEMBYLD (apitegromab-mstn), the First and Only Muscle-Targeted Treatment for Children and Adults with Spinal Muscular Atrophy (SMA) (Businesswire) - "The approval of ISEMBYLD was based on positive results from the Phase 3 pivotal, randomized, double-blind, placebo-controlled SAPPHIRE study....ISEMBYLD U.S. commercial launch underway with product available to ship in the coming days..."

FDA approval • Launch US • Muscular Atrophy

Scholar Rock Receives FDA Fast Track Designation for Apitegromab Facioscapulohumeral Muscular Dystrophy (FSHD) Program as Participant Dosing Commences in Phase 2 FORGE Trial (Businesswire) - "FORGE is a Phase 2 randomized, double-blind, placebo-controlled, multi-center clinical trial designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of apitegromab as a monotherapy in adults with genetically confirmed FSHD (NCT07435129). The study will enroll approximately 60 participants randomized one-to-one to receive apitegromab 10 mg/kg or placebo intravenously every four weeks for 52 weeks."

Fast track • Trial status • Muscular Dystrophy

Scholar Rock is also preparing to expand the regulatory program into Japan (AllSci Corp) - "The Pharmaceuticals and Medical Devices Agency agreed that no additional Japanese clinical studies will be required for a Japanese New Drug Application, allowing the company to target a submission by the end of 2026."

Japan filing • Muscular Atrophy

Scholar Rock said August 24 it has withdrawn the European marketing application for spinal muscular atrophy drug apitegromab after a manufacturing site received an adverse US FDA inspection classification (AllSci Corp) - "US review remains on track for a September 30, 2026 PDUFA date....The Massachusetts biotech removed Catalent Indiana LLC, now part of Novo Nordisk, from its US Biologics License Application under US FDA guidance and will rely solely on an alternate US fill-finish facility. Catalent Indiana received an Official Action Indicated classification following an April 2026 site inspection....Scholar Rock...plans to resubmit using the alternate facility."

EMA filing • PDUFA • Muscular Atrophy

Maximizing Metabolic Synergy: A Review of Dual Incretin Therapy as a Step-Up Strategy Following Glucagon-Like Peptide-1 (GLP-1) Monotherapy Failure or Optimization. (PubMed, Cureus) - "Based on this review, evidence from head-to-head and insulin-comparator trials demonstrates that dual GIP/GLP-1 co-agonism consistently overcomes metabolic plateaus that result from single-pathway therapy, producing superior glycated hemoglobin reduction, bariatric-level weight loss (up to 25.3%), and robust macrovascular and heart failure protection, including a 38% reduction in composite cardiovascular risk among patients with heart failure with preserved ejection fraction (HFpEF). Furthermore, recent phase 2 data demonstrate that the lean mass loss associated with profound weight loss can be pharmacologically managed; when tirzepatide is paired with the anti-myostatin agent apitegromab, sarcopenic risk is mitigated by nearly halving lean mass loss compared with dual-incretin monotherapy (14.6% vs. 30.2%), though whether this muscle-sparing synergy extends to single-pathway GLP-1 agents remains unverified. The transition from single-pathway GLP-1R agonism to dual..."

Journal • Monotherapy • Review • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Type 2 Diabetes Mellitus

Phase 2 Study Evaluating Apitegromab for the Treatment of FSHD (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Scholar Rock, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Muscular Dystrophy

Business Highlights and Upcoming Milestones (Businesswire) - "Apitegromab Biologics License Application (BLA) on track for potential FDA approval by September 30, 2026 Prescription Drug User Fee Act (PDUFA) date...The EMA is reviewing the apitegromab MAA, which includes the Catalent Indiana fill-finish facility, and is awaiting the FDA inspection classification of Catalent Indiana. In parallel, Scholar Rock is engaging with the EMA on next steps, including the potential to add the Company’s second fill-finish facility to the MAA. The Company plans to provide updated guidance on timelines for a Committee for Medicinal Products for Human Use (CHMP) opinion upon alignment with the EMA."

EMA filing • PDUFA • Muscular Atrophy

Scholar Rock Provides Update on Timing of Committee for Medicinal Products for Human Use (CHMP) Opinion for Apitegromab Marketing Authorisation Application (MAA) for Spinal Muscular Atrophy (SMA) (Businesswire) - "Should the FDA reclassify Catalent Indiana, a CHMP opinion would be expected later in 2026. In the event that Catalent Indiana is not reclassified, Scholar Rock will work with the EMA to advance the apitegromab MAA with the Company’s second fill-finish facility, which is included in the apitegromab Biologics License Application (BLA) under FDA review in the U.S. with a September 30, 2026 Prescription Drug User Fee Act (PDUFA) action date. The Company will provide an update during its second quarter earnings call on Thursday, August 6, 2026."

CHMP • PDUFA • Muscular Atrophy

Trial Design for the Phase 2 FORGE Study Evaluating Apitegromab in Adults With FSHD (ICNMD 2026) - P2, P3 | "In previous clinical studies for spinal muscular atrophy (Phase 2 TOPAZ, NCT03921528; Phase 3 SAPPHIRE, NCT05156320), the muscle-targeted treatment led to clinically meaningful and statistically significant improvements in motor function and was well tolerated across a broad range of patients who were also receiving a survival motor neuron-targeted treatment (nusinersen or risdiplam). Supported by the pivotal outcomes from previous clinical and preclinical work, the FORGE study will investigate apitegromab, an investigational muscle-targeted treatment, in the adult FSHD patient population. FORGE is expected to be conducted across 20 sites in North America and Europe."

Clinical • P2 data • Genetic Disorders • Immunology • Movement Disorders • Muscular Atrophy • Muscular Dystrophy • Rare Diseases

Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial. (PubMed, Nat Med) - P2 | "In the randomized, double-blind, placebo-controlled phase 2 EMBRAZE study, adults with overweight or obesity (n = 102) were randomized 1:1 to receive tirzepatide plus apitegromab (10 mg kg-1) or tirzepatide plus placebo. In summary, this proof-of-concept study demonstrated that selective targeting of myostatin by apitegromab was well tolerated and effective in preserving lean mass when combined with tirzepatide. ClinicalTrials.gov identifier: NCT06445075 ."

Clinical • Journal • P2 data • Genetic Disorders • Obesity

Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial (Nature) - "At week 24, apitegromab resulted in a least square mean (80% confidence interval (CI)) of 1.9 (1.2−2.7) kg less lean mass loss than placebo (P = 0.001), despite similar total body weight loss between groups, representing a 54.9% retention of lean mass relative to placebo. In participants receiving apitegromab, trough concentrations of apitegromab and total latent myostatin, a pharmacodynamic marker, both increased over time and reached a plateau after approximately 16 weeks. Incidence of adverse events (AEs) (% (95% CI)) was generally similar across apitegromab-treated participants and placebo-treated participants, with 39 of 51 (76% (63−86%)) and 36 of 51 (71% (57−81%)) participants experiencing an AE, respectively."

P2 data • Obesity

Scholar Rock Reports First Quarter 2026 Financial Results and Recent Business Highlights (Businesswire) - "FDA accepted apitegromab Biologics License Application (BLA) for treatment of children and adults with spinal muscular atrophy (SMA) with September 30, 2026 Prescription Drug User Fee Act (PDUFA) action date...A Committee for Medicinal Products for Human Use (CHMP) opinion for the apitegromab Marketing Authorisation Application (MAA) is anticipated near mid-2026."

CHMP • PDUFA • Muscular Atrophy

Scholar Rock Resubmits Biologics License Application (BLA) to FDA for Apitegromab for Treatment of Children and Adults with Spinal Muscular Atrophy (SMA) (Yahoo Finance) - "During the meeting and an FDA site visit that followed, no additional corrective actions were requested by the FDA to Novo Nordisk’s remediation plan. The decision to resubmit the apitegromab BLA prior to FDA reinspection of Catalent Indiana was made in alignment with the FDA...Following a positive Type C meeting on March 3, 2026, Scholar Rock aligned with the FDA to include the additional facility in the BLA resubmission based on the Company’s accelerated commercial fill-finish timelines...A PDUFA action date is expected in late September 2026."

FDA approval • FDA filing • Muscular Atrophy

FSHD Program (Businesswire) - "The IND application is cleared, and the Company continues to anticipate the initiation of a Phase 2 randomized, double-blind, placebo-controlled trial, called FORGE, in mid-2026."

Trial status • Muscular Dystrophy

SMA Program:...European Medicines Agency (EMA) regulatory review ongoing (Businesswire) - "A decision by EMA on the apitegromab Marketing Authorisation Application (MAA) is expected in mid-2026....The Company is planning for an apitegromab launch in Europe in the second half of 2026, beginning with Germany."

EMA approval • Launch Europe • Muscular Atrophy

SMA Program: BLA resubmission and U.S. launch, following approval, expected in 2026 (Businesswire) - "A meeting between FDA and Catalent Indiana occurred early in the first quarter of 2026. The meeting was constructive and included a discussion of Novo Nordisk’s progress remediating the Catalent Indiana facility. No additional corrective actions were requested by FDA. Scholar Rock plans to resubmit the apitegromab BLA following a successful reinspection of the site."

FDA event • FDA filing • Launch US • Muscular Atrophy

SRK-015-005: A Study to Evaluate How Apitegromab Works in Subjects Who Are Less Than 2 Years Old and Have Spinal Muscular Atrophy (clinicaltrialsregister.eu) - P1/2 | N=30 | Recruiting | Sponsor: Scholar Rock Inc.

New P1/2 trial • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMN1 • SMN2

Phase 2 Study Evaluating Apitegromab for the Treatment of FSHD (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Scholar Rock, Inc.

New P2 trial • Muscular Dystrophy

Advancing treatment of spinal muscular atrophy through inhibition of the myostatin signaling pathway. (PubMed, Expert Rev Neurother) - "Treatments that inhibit myostatin signaling represent a potential complementary pathway for direct muscle enhancement. In the evolving SMA treatment landscape, understanding how muscle-targeted treatment can be incorporated into clinical practice will facilitate individualized treatment decisions and identify outcomes that best encapsulate maintenance or improvement of motor function across the phenotypic spectrum of SMA."

Journal • Review • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

After FDA meeting, Scholar Rock to again seek apitegromab approval (SMA News Today) - "Agency rejected initial application for SMA drug; developer to resubmit in 2026...First, Scholar Rock will work with its third-party fill-finish facility Catalent Indiana — which is tasked with the final steps of the drug’s packaging, such as ensuring the product is sterile — to address concerns raised by the FDA...Per the developer, the fill-finish facility expects to be ready for inspection by the end of the year. Scholar Rock would then resubmit its application, with the goal of making apitegromab commercially available to SMA patients before the end of 2026....Scholar Rock has also applied for approval of apitegromab for use in the European Union. Review of that application is ongoing, with a decision expected in mid-2026, the company said....Scholar Rock’s applications seeking approval of apitegromab were based on positive data from the Phase 3 SAPPHIRE clinical trial (NCT05156320)..."

EMA approval • FDA filing • Launch US • Muscular Atrophy

A plain language summary of the SAPPHIRE clinical trial of apitegromab in children and young adults with spinal muscular atrophy. (PubMed, Expert Rev Neurother) - No abstract available

Journal • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Pharmacological intervention: Challenges and promising outcomes for fat loss and preservation of lean body mass in the treatment of overweight and type 2 diabetes. (PubMed, Diabetes Obes Metab) - "Activin II receptor inhibition with bimagrumab demonstrated significant preservation and increases in LBM, along with FM reduction, in both preclinical and phase 2 studies in individuals with overweight and T2D. Similar effects were observed for myostatin and activin A inhibitors (trevogrumab, garetosmab), latent myostatin inhibitors (apitegromab, SRK-439), and Selective Androgen Receptor Modulators (enobosarm)...Pharmacological adjunct therapies show potential for improving body composition and physical function during GLP-1 RA-induced weight loss. Preliminary findings are promising, but larger, controlled trials are necessary to confirm efficacy and safety before clinical implementation can be considered."

Journal • Review • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

OPAL: A Study to Evaluate How Apitegromab Works in Subjects Who Are Less Than 2 Years Old and Have Spinal Muscular Atrophy (clinicaltrials.gov) - P2 | N=52 | Recruiting | Sponsor: Scholar Rock, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Safety and efficacy of apitegromab in nonambulatory type 2 or type 3 spinal muscular atrophy (SAPPHIRE): a phase 3, double-blind, randomised, placebo-controlled trial. (PubMed, Lancet Neurol) - P3 | "Participants in the apitegromab treatment groups (combined 20 mg/kg and 10 mg/kg dose) achieved statistically significant improvements in motor function compared with placebo; however, the least squares mean difference was not significant between apitegromab 20 mg/kg and placebo. Overall, SAPPHIRE results build on findings from the phase 2 TOPAZ trial, showing improved motor function with a generally well tolerated safety profile, supporting the use of muscle-targeting therapy for spinal muscular atrophy."

Journal • P3 data • Cough • Genetic Disorders • Infectious Disease • Movement Disorders • Muscular Atrophy • Pain • Rare Diseases • Respiratory Diseases

EMBRAZE: Efficacy and Safety of Apitegromab for the Treatment of Adults Who Are Overweight or Obese (clinicaltrials.gov) - P2 | N=102 | Completed | Sponsor: Scholar Rock, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Oct 2025 ➔ Jun 2025 | Trial primary completion date: Jun 2025 ➔ Mar 2025

Trial completion • Trial completion date • Trial primary completion date • Genetic Disorders • Obesity