GDF-8: A New Era in Muscle Growth Therapies is Coming to Market

On November 14, 2025, Scholar Rock released its third-quarter financial and pipeline update, announcing that it had held a constructive, face-to-face Type A meeting with the FDA regarding the BLA for its core asset, Apitegromab, intended for the treatment of spinal muscular atrophy (SMA) in both children and adults. The contract manufacturer Catalent also attended the meeting and presented the progress made in executing its remediation plan, while confirming to the FDA that the manufacturing site would be ready for re-inspection by the end of the year. Scholar Rock expects to resubmit the BLA in 2026 and to launch Apitegromab commercially in the United States following approval.

Source: Scholar Rock Official Website [1]

Apitegromab is a fully human antibody inhibitor targeting myostatin (also known as GDF-8). On October 7, 2024, it was announced that the Phase 3 SAPPHIRE trial in SMA met its primary endpoint. The announcement also noted that Scholar Rock’s next-generation GDF-8 inhibitor, SRK-439, has received IND clearance and will begin dosing in healthy volunteers in Q4 2025. This latest update on the GDF-8 pipeline marks another step forward in advancing GDF-8 from the clinic toward commercialization.

Functions and Signaling Pathway of GDF-8

GDF-8 (Growth Differentiation Factor 8), or Myostatin, is a protein primarily expressed by skeletal muscle cells. As a member of the transforming growth factor-β (TGF-β) superfamily, GDF-8 controls muscle mass by suppressing the proliferation of muscle cells, maintaining muscle volume within a stable range. Under various pathological conditions such as muscular dystrophy, chronic kidney disease, cancer, liver disease, obesity, and injuries like anterior cruciate ligament (ACL) tears, GDF-8 levels may increase.

Mature GDF-8 is formed through a series of proteolytic steps. After the GDF-8 precursor is synthesized in cells, signal peptidase first removes the signal peptide, generating Pro-GDF-8. Then, the proprotein convertase Furin recognizes and cleaves a specific sequence in Pro-GDF-8 to form Latent GDF-8, a key step in GDF-8 maturation. Finally, BMP-1 or Tolloid metalloproteinases further process Latent GDF-8, likely involving cleavage of the prodomain, thereby activating GDF-8. Mature GDF-8 exists as a homodimer, a structural feature essential for its biological activity.

The process of GDF-8 maturation [2]

The primary downstream receptor of GDF-8 is Activin type II receptor (Activin RII). Upon binding to this receptor, GDF-8 recruits Activin type I receptors, which regulates intracellular signaling pathways such as SMAD and AKT. These signals alter transcription and promote degradation of muscle-related proteins, ultimately leading to muscle loss.

GDF-8 Signaling Pathway [3]

Current Landscape of GDF-8-Targeted Drug Development

The Apitegromab (SRK-015) is a fully humanized IgG4λ monoclonal antibody that binds specifically to Pro GDF-8 or Latent GDF-8, inhibiting activation without binding to mature GDF-8 or other related growth factors. By blocking GDF-8 before its release, this mechanism offers high selectivity and fewer side effects.

Mechanism of Apitegromab [4]

Another program is Roche’s monoclonal antibody Emugrobart (RO7204239, GYM329, RG6237), an engineered SMART-Ig (Sequential Monoclonal Antibody Recycling Technology - Immunoglobulin). It removes latent GDF-8 from plasma and tissues and has the potential to improve symptoms associated with muscle atrophy and muscle weakness. GYM329 is currently being evaluated in clinical trials for SMA and facioscapulohumeral muscular dystrophy, among other indications.

For drugs targeting mature GDF-8, Regeneron has developed Trevogrumab (REGN-1033). On September 17, 2025, Regeneron announced Phase 2 results evaluating whether combining Trevogrumab with Semaglutide could help maintain weight-loss efficacy by increasing muscle mass. The complete 26-week results showed that the combination helped prevent roughly half of the lean mass loss associated with Semaglutide, while further reducing fat mass. All treatment groups demonstrated significant metabolic and lipid improvements, including waist circumference, blood pressure, cholesterol, triglycerides, and HbA1c.

Source: Regeneron Official Website [5]

There are also ligand-trap approaches. For example, KER-065 from Keros is a fusion protein combining Activin RII with an Fc domain. It captures GDF-8 or Activin A, increasing muscle mass and reducing fat mass to treat obesity. It can be used alone or in combination with GLP-1 receptor agonists.

Source: Keros Official Website [6]

GDF-8 has thus become a major target for developing therapies that promote muscle growth or treat muscle-wasting conditions. Many drug candidates target non-mature forms of GDF-8 to control its activation, while those targeting the mature form offer more direct regulation of muscle growth. The optimal design strategy depends on the mechanism of action, safety, efficacy, and potential side effects.

KACTUS High-Quality GDF-8 Proteins

To support drug development across diseases involving muscle wasting, KACTUS has built a comprehensive portfolio of high-quality GDF-8 and related proteins, including Pro, Latent, and Mature forms as well as the exclusive supply of biotinylated mature GDF-8. These products cover multiple species and diverse tag designs, and all undergo rigorous quality control. They are suitable for various stages of drug screening and validation.

Product Validation

Determined by its ability to inhibit the proliferation of MPC-11 cells. The expected ED50 for this effect is <30 ng/ml (QC Test).

Immobilized Human Latent GDF-8, His Tag at 1 μg/ml (100 μl/well) on the plate. Dose response curve for Apitegromab, hFc Tag with the EC50 of 23.1 ng/ml determined by ELISA (QC Test).

Immobilized Human/Cynomolgus Activin RIIB, His Tag at 1 μg/ml (100 μl/well) on the plate. Dose response curve for Biotinylated Human/Mouse/Rat GDF-8, Avi Tag with the EC50 of 2.5 ng/ml determined by ELISA (QC Test).

Product List

References:

[1]https://investors.scholarrock.com/news-releases/news-release-details/scholar-rock-reports-third-quarter-2025-financial-results-and/

[2]Circulating Growth Differentiation Factor 11/8 Levels Decline With Age. Circ Res. 2016 Jan 8;118(1):29-37. doi: 10.1161/CIRCRESAHA.115.307521.

[3]Garber K. No longer going to waste. Nat Biotechnol. 2016 May 6;34(5):458-61. doi: 10.1038/nbt.3557.

[4]https://scholarrock.com/wp-content/uploads/2025/10/Tirucherai-WMS-2025.pdf#toolbar=0

[5]https://investor.regeneron.com/node/31266/pdf

[6]https://ir.kerostx.com/static-files/d666096b-07f9-47ea-b9ad-205f7c89895f