BHV-2000; BMS-986089; RG6206; RO7239361 · Evidence-based safety and harm-reduction overview.
| Also known as | BHV-2000; BMS-986089; RG6206; RO7239361 |
| Category | Peptide (research chemical) |
| Drug class | Anti-myostatin adnectin-Fc fusion protein (recombinant biologic; not a monoclonal antibody) |
| Primary target | Mature myostatin (GDF-8) C-terminal domain; also antagonizes ActRIIB/activin A signaling |
| Development codes | BHV-2000 (Biohaven); BMS-986089 (Bristol Myers Squibb); RG6206 / RO7239361 (Roche) |
| DMD program outcome | Terminated November 2019 after Phase 2/3 futility analysis; 0.12-point NSAA difference vs placebo, not significant |
| SMA Phase 3 (RESILIENT) status | Primary endpoint (MFM-32 at Week 48) did not statistically separate from placebo+SOC; 97% enrolled in open-label extension; FDA Fast Track Designation granted 2024 |
| Obesity program | Phase 2 enrollment completed as of 2024; human efficacy data not yet publicly reported; preclinical data showed reduced fat and increased lean mass in animals |
| US legal status | Not FDA-approved. Taldefgrobep alfa is an investigational biologic not approved for any indication in the United States. It is not available for commercial or clinical use outside of sponsored trials. Received FDA Fast Track Designation for spinal muscular atrophy (SMA) in 2024, which facilitates development and review but confers no approval status. Not a dietary supplement; not for human consumption outside a clinical trial context. |
Taldefgrobep alfa is a fully human recombinant anti-myostatin adnectin-Fc fusion protein. It is not a monoclonal antibody; rather, it fuses an engineered adnectin domain (a fibronectin-based binding scaffold) to an IgG1-Fc domain. The adnectin domain binds directly to mature myostatin (GDF-8), blocking its interaction with downstream signaling machinery. Originally developed by Bristol Myers Squibb (as BMS-986089), the program was licensed to Biohaven Pharmaceuticals and is also associated with Roche development codes. The compound has been evaluated in Duchenne muscular dystrophy (DMD, program terminated), spinal muscular atrophy (SMA, Phase 3 RESILIENT trial), and obesity (Phase 2 enrollment completed as of 2024).
Taldefgrobep alfa binds to the C-terminal region of mature myostatin (GDF-8) and to the ActRIIB-myostatin complex. By occupying this binding site, it prevents recruitment of activin-like kinase-4/5 (ALK4/5) and the resulting phosphorylation of Smad2/3, which is the canonical pathway through which myostatin suppresses skeletal muscle growth and promotes adipogenesis. The construct achieves dual-pathway inhibition by antagonizing both myostatin and activin A signaling through the activin type IIB receptor (ActRIIB). This simultaneously reduces free myostatin levels and blunts activin signaling, both of which regulate skeletal muscle mass and adipose tissue. The Fc fusion extends circulating half-life, supporting infrequent subcutaneous dosing in trials.
Myostatin was identified as a negative regulator of muscle mass in 1997 (knockout mice developed dramatically enlarged musculature), generating sustained pharmaceutical interest in inhibition strategies across muscular dystrophies, sarcopenia, and cachexia. Bristol Myers Squibb developed the adnectin-based inhibitor approach as an alternative to monoclonal antibodies, producing BMS-986089, later assigned Roche development codes RG6206/RO7239361. Phase 1 trials in healthy volunteers and Phase 1b/2 trials in DMD patients demonstrated pharmacodynamic activity and a favorable early safety profile. A larger Phase 2/3 trial in ambulatory DMD patients (n=166) failed to achieve its primary functional endpoint on the North Star Ambulatory Assessment (NSAA) scale after futility analysis; BMS terminated the DMD program in November 2019. Biohaven subsequently licensed the compound and repositioned it for SMA, initiating the Phase 3 RESILIENT trial (NCT05337553). Biohaven also initiated a Phase 2 obesity trial based on preclinical data showing fat reduction and lean mass increases. As of 2024-2025, the SMA Phase 3 primary endpoint (MFM-32 at 48 weeks) did not achieve statistical separation from placebo plus standard of care, though clinically meaningful improvements were noted at assessed timepoints and 97% of subjects enrolled in the open-label extension.
Evidence base spans preclinical animal studies, a Phase 1 trial in healthy volunteers (n=97), a Phase 1b/2 trial in DMD patients (n=43, ages 5-11), a terminated Phase 2/3 DMD trial (n=166), the active Phase 3 RESILIENT SMA trial, and a Phase 2 obesity trial with enrollment completed as of 2024.
Preclinical: Statistically significant decreases in free myostatin and increases in lower limb muscle volume were demonstrated in severe combined immunodeficient mice, juvenile rats, and adolescent cynomolgus monkeys. Muscle volume increases of approximately 30% were observed in rodents; approximately 5% in cynomolgus monkeys.
Phase 1 (healthy volunteers, n=97): Achieved greater than or equal to 90% free myostatin suppression across all doses tested. Statistically significant thigh muscle volume increases of 3.41% to 4.75% were measured. Drug was generally well tolerated.
Phase 1b/2 (DMD, n=43): Lean body mass increase of 1.75%; contractile muscle area increased 5.45% in the treatment arm versus a decrease of 0.79% in placebo. No serious adverse events were reported.
Phase 2/3 (DMD, n=166, ambulatory, terminated): Failed primary endpoint. The difference on the NSAA functional scale was 0.12 points versus placebo, which was not clinically or statistically meaningful. Program terminated November 2019 after futility analysis.
Phase 3 RESILIENT (SMA, ages 4-21): 48-week double-blind phase with 48-week open-label extension. Primary endpoint (MFM-32 change at Week 48) did not achieve statistical separation from placebo plus standard of care. No treatment-related serious adverse events; 97% of subjects continued into the open-label extension. Ongoing; results are being evaluated and may prompt repositioning considerations.
Phase 2 obesity: Enrollment completed as of 2024; results not yet publicly reported. Preclinical data presented at ObesityWeek showed reductions in fat mass and increases in lean mass in animal models.
Published clinical trials evaluated subcutaneous administration on weekly or every-two-week schedules across a range of weight-based and fixed doses. Phase 1 data established pharmacodynamic activity (myostatin suppression greater than or equal to 90%) across the evaluated dose range. Specific dose levels used in trials are reported in primary literature and on ClinicalTrials.gov. This information is provided for scientific reference only and does not constitute a dosing protocol. Taldefgrobep alfa is not approved and is not available outside clinical trials. Consult a qualified clinician and refer to official trial protocols for any clinical question.
This is general research/context information, not medical advice or a recommended protocol.
No stacking data in humans. In the SMA RESILIENT trial, some subjects were on approved SMA disease-modifying therapies (nusinersen, risdiplam) as standard of care alongside taldefgrobep alfa; interaction or additive efficacy data from that combination are not separately reported in public summaries. Preclinical combination data are not publicly available. Any combination use outside a clinical protocol is unstudied and not supportable on current evidence.
Creatine Supreme. For supporting muscle mass and strength, creatine monohydrate is the most evidence-backed legal option, with decades of safety data - ours ships from the Peptropix line.
See our recommended pickOrder your own bloodwork online — hormone, metabolic and inflammation panels, no doctor visit needed. Know your baselines before and during any protocol. Independent bloodwork is the cheapest insurance there is.
Get tested with Ulta Lab Tests →Taldefgrobep alfa is a recombinant fusion protein that uses an adnectin domain - a binding scaffold derived from the tenth type III domain of human fibronectin - rather than an antibody variable region. It is fused to an IgG1-Fc domain to extend its half-life. This architecture targets myostatin (GDF-8) at the C-terminal domain and also antagonizes ActRIIB signaling, which distinguishes it mechanistically from antibody-based myostatin inhibitors.
Early-phase trials in DMD patients demonstrated modest increases in lean body mass and contractile muscle area with an acceptable safety profile. However, the larger Phase 2/3 trial in ambulatory DMD patients (n=166) showed only a 0.12-point difference on the North Star Ambulatory Assessment (NSAA) functional scale versus placebo, which was not clinically or statistically meaningful. A pre-specified futility analysis concluded that continuing the trial was unlikely to demonstrate efficacy, and Bristol Myers Squibb terminated the program in November 2019. This outcome is consistent with a broader pattern in neuromuscular disease trials where biomarker and imaging improvements do not always translate to functional benefit.
The Phase 3 RESILIENT trial (NCT05337553) enrolled patients ages 4-21 with SMA across a 48-week double-blind phase followed by a 48-week open-label extension. The primary endpoint - change in Motor Function Measure 32 (MFM-32) score at Week 48 compared to placebo plus standard of care - did not achieve statistical significance. Clinically meaningful improvements were noted at assessed timepoints and 97% of subjects continued into the open-label extension, suggesting some functional signal. No treatment-related serious adverse events were reported. As of the available evidence, the program may require repositioning or a revised development strategy. Biohaven received FDA Fast Track Designation for the SMA indication in 2024.
Preclinical data presented at ObesityWeek demonstrated reductions in fat mass and increases in lean mass in animal models, consistent with the known role of myostatin and activin signaling in both skeletal muscle and adipose tissue biology. On this basis, Biohaven initiated a Phase 2 clinical trial in obesity, which completed enrollment as of 2024. Human efficacy and safety data from that trial are not yet publicly reported. The preclinical findings are hypothesis-generating but cannot be extrapolated directly to human outcomes.
No. Taldefgrobep alfa is an unapproved investigational biologic with no approved indication in the United States or elsewhere. It is not sold commercially, is not available through supplement channels, and has no legitimate consumer supply chain. Any material marketed as this compound outside a licensed clinical trial cannot be verified for identity, purity, or safety.
Providing a dosing recommendation is outside the scope of this reference entry. Published trial protocols and primary literature describe weight-based and fixed subcutaneous dosing schedules used in clinical studies; those details are accessible via ClinicalTrials.gov (NCT05337553) and published clinical pharmacology reports. Use of this compound requires enrollment in a clinical trial or direct supervision by a qualified clinician with access to the investigational drug under appropriate regulatory authorization.
Medical & legal disclaimer. This site is for informational and harm-reduction purposes only. It is not medical advice and is not a substitute for a licensed healthcare professional. The compounds discussed are largely not approved by the FDA for human use and many are sold strictly as research chemicals 'not for human consumption.' Nothing here is an endorsement to purchase, possess, or use any substance. Laws vary by jurisdiction. Always consult a qualified physician and follow the law where you live.
Some links on this page may be affiliate links. If you buy through them we may earn a commission at no extra cost to you. This never changes the safety information we publish.