Ostarine (MK-2866 / Enobosarm) — Evidence Review

What it is

Ostarine (developmental code MK-2866; International Nonproprietary Name enobosarm; also GTx-024, S-22) is an orally bioavailable nonsteroidal selective androgen receptor modulator originally developed by GTx Inc. and now advanced by Veru Inc. It is the single most clinically studied compound in the SARM class, having gone through multiple randomized controlled trials for cancer-associated muscle wasting (cachexia), androgen-receptor-positive breast cancer, and — most recently — preservation of muscle during GLP-1 (semaglutide) weight loss. Despite roughly two decades of clinical development, ostarine/enobosarm is NOT an approved drug in any country and remains investigational. In the United States it is an unapproved drug that cannot legally be sold as a dietary supplement, yet it is widely and illegally sold online as a bodybuilding "research chemical," which is the context in which most consumer harm reports arise.

How it works

Ostarine binds the androgen receptor and acts as a tissue-selective agonist. Being nonsteroidal, it is engineered to produce anabolic effects in muscle and bone while causing comparatively little androgenic activity in the prostate and skin; in its clinical program, lean-mass gains occurred without reported prostate effects, virilization, or hirsutism. The proposed basis for selectivity is tissue-specific AR coregulator recruitment and differential receptor conformation/signaling in muscle versus reproductive tissue, though the exact molecular determinants remain incompletely characterized.

Efficacy — what the human evidence shows

The Institute grades each claimed effect by the strength of the human evidence behind it. Grades are assigned independently for benefit and for harm.

Increase / preservation of lean body mass (DXA surrogate)Established

Enobosarm's ability to raise or preserve DXA-measured lean body mass versus placebo is the most reproducibly demonstrated effect, replicated across a Phase 2 cachexia trial and two Phase 3 NSCLC trials, plus a recent Phase 2b GLP-1 study. Important caveat: this is a body-composition surrogate that has NOT reliably translated into proven functional or clinical benefit.

Phase 2 cancer cachexia RCT (Dobs et al., Lancet Oncology 2013, ~159 pts, 1 mg and 3 mg) met its primary lean-body-mass endpoint. Both Phase 3 POWER trials (GTx, 2013; ~300 pts each, 3 mg vs placebo in NSCLC) showed a statistically significant quantitative LBM advantage over placebo. Phase 2b QUALITY (Veru, 168 pts ≥60 yr on semaglutide) met its primary endpoint of lean-mass preservation, with ~99% of weight loss attributable to fat.

Improvement in physical function / muscle strengthInsufficient

Despite the lean-mass gains, a clinically meaningful improvement in physical function has NOT been established — the best-powered trials were negative on this outcome. This is the central reason ostarine never reached market for muscle wasting.

The pivotal Phase 3 POWER trials failed the co-primary responder endpoint of physical function (stair-climb power); enobosarm improved lean mass but 'was not effective in improving muscle strength.' Development for cachexia was terminated and no approval followed. The earlier Phase 2 showed some function signal, but it was not confirmed. The QUALITY Phase 2b reported fewer patients with ≥10% stair-climb-power decline (secondary endpoint), which is supportive but not confirmatory.

Antitumor activity in AR+/ER+/HER2- advanced breast cancerProbable

Enobosarm shows genuine but modest single-agent antitumor activity in previously treated AR+/ER+/HER2- breast cancer; a randomized Phase 2 met a clinical-benefit signal, but the confirmatory Phase 3 was discontinued before it could establish efficacy.

Randomized open-label Phase 2 (Study G200802, Palmieri et al., Lancet Oncology 2024; 136 pts, 9 mg vs 18 mg) reported a clinical benefit rate of ~32% (9 mg) and ~29% (18 mg) at 24 weeks with low-grade, manageable toxicity; no added benefit at 18 mg. The Phase 3 ARTEST trial (NCT04869943) was discontinued with only 34 evaluable patients randomized (ORR 12.5% enobosarm vs 0% control) — underpowered and inconclusive.

Muscle preservation during GLP-1 (semaglutide) weight lossProbable

Adding enobosarm to semaglutide preserved lean mass and shifted weight loss toward fat in a positive Phase 2b trial — the current lead indication — but this rests on surrogate body-composition endpoints and has not yet been confirmed in Phase 3 or approved.

Phase 2b QUALITY (Veru; 168 adults ≥60, enobosarm 3 mg/6 mg vs placebo added to WEGOVY/semaglutide): met primary lean-mass endpoint (positive topline Jan 2025; safety May 2025), ~99% of weight loss as fat, and ~54.5% fewer patients with ≥10% stair-climb-power decline vs placebo. 3 mg selected for a planned Phase 3; End-of-Phase-2 FDA meeting sought for Q3 2025. Not yet Phase 3-proven or approved.

Safety signals

Harm signals are reported prominently even where the evidence grade is low. Absence of evidence is not evidence of safety.

Cholestatic drug-induced liver injury (hepatotoxicity)Probable

Ostarine is repeatedly implicated in human liver injury, typically a cholestatic pattern (jaundice, itching, dark urine) with onset usually 2-3 months after starting, though the range spans a few weeks to a year (NIH LiverTox). Most reported cases involve unregulated consumer products, which are frequently adulterated, but the signal is consistent across case reports and pharmacovigilance databases; the FDA lists liver injury and acute liver failure among SARM risks.

Cardiovascular risk — HDL/lipid suppressionProbable

Enobosarm lowers HDL cholesterol and alters lipids in controlled trials, a recognized class effect of AR agonists. FDA warns of increased heart attack and stroke risk with SARMs; direct causal human cardiovascular-event evidence is thinner (isolated reports including a fatal cardiac-death case and a myocarditis case in the broader SARM literature), so the hard-endpoint risk is a plausible concern rather than a proven rate.

Hypothalamic-pituitary-gonadal (HPG) axis suppressionPreliminary

In its clinical program ostarine lowered total testosterone, largely because it reduces SHBG rather than through central shutdown: in a Phase 2 study in healthy men (Dalton 2011) total testosterone and SHBG fell at 1-3 mg/day while free testosterone, LH and FSH did not change significantly. Suppression of the hypothalamic-pituitary-gonadal axis, testicular shrinkage and reduced fertility are recognised on-target risks of androgen-receptor agonists and are reported at the higher doses used recreationally, but were not demonstrated in the low-dose trials.

Other serious adverse events reported to FDA (psychosis/hallucinations, sleep disturbance, sexual dysfunction, infertility, miscarriage)Preliminary

FDA's SARM adverse-event reporting attributes psychosis/hallucinations, sleep disturbances, sexual dysfunction, infertility, and pregnancy miscarriage to SARMs as a class. These derive from uncontrolled adverse-event reports and case series, not controlled trials, but represent real safety signals that absence of trial data does not rule out.

Product contamination and mislabelingEstablished

Consumer 'ostarine' products are frequently mislabeled, underdosed, overdosed, or adulterated with other undeclared drugs; analytical surveys and FDA testing document that many SARM products do not contain what the label claims, compounding every other risk and driving inadvertent anti-doping violations.

Human trials on record

Study / registry	Phase	Population	Key result
Dobs et al., Lancet Oncology 2013 (NCT00467844)	Phase 2	~159 patients with NSCLC, colorectal cancer, non-Hodgkin lymphoma, CLL, or breast cancer at risk of/with cachexia	Met primary endpoint: enobosarm 1 mg and 3 mg significantly increased total lean body mass vs placebo, with a signal for improved physical function; well tolerated without androgenic toxicity.
POWER 1 & POWER 2 (GTx, reported 2013)	Phase 3	~300 patients each (~600 total) with stage III/IV NSCLC starting first-line chemotherapy; enobosarm 3 mg/day vs placebo	FAILED the co-primary responder endpoints agreed with FDA. Significant lean-body-mass benefit vs placebo, but NO improvement in physical function (stair-climb power). Development for cachexia terminated; no approval.
Study G200802 / Palmieri et al., Lancet Oncology 2024 (PMID 38342115)	Phase 2 (randomized, open-label)	136 patients with previously treated AR+/ER+/HER2- locally advanced or metastatic breast cancer; 9 mg (n=72) vs 18 mg (n=64)	Clinical benefit rate ~32% (9 mg) and ~29% (18 mg) at 24 weeks; antitumor activity with low-grade, manageable adverse events; no added benefit at 18 mg.
ARTEST (NCT04869943, Veru)	Phase 3	AR+/ER+/HER2- metastatic breast cancer, enobosarm 9 mg monotherapy vs active control; discontinued	Discontinued for strategic reprioritization with only 34 evaluable patients randomized; ORR 12.5% (2/16) enobosarm vs 0% (0/18) control — underpowered and inconclusive, not a completed efficacy read-out.
QUALITY Phase 2b (Veru, topline 2025)	Phase 2b	168 adults ≥60 yr, overweight/obese, on semaglutide (WEGOVY); enobosarm 3 mg/6 mg vs placebo	Met primary endpoint of lean-mass preservation; ~99% of weight loss was fat; ~54.5% fewer patients with ≥10% stair-climb-power decline vs placebo. 3 mg advanced toward Phase 3; not yet approved.

Legal & regulatory status

United States

Unapproved investigational drug — NOT FDA-approved for any indication as of July 2026. FDA states SARMs are unapproved drugs that cannot legally be sold as dietary supplements or 'for research use only'; FDA has issued consumer warnings (most recent major consumer update April 2023) and multiple warning letters to companies selling ostarine. Enobosarm has received FDA Fast Track designation for AR+/ER+/HER2- metastatic breast cancer, but Fast Track is a development-facilitation status, not approval.

Anti-doping (WADA)

Prohibited at all times (in- and out-of-competition) under Section S1.2 'Other Anabolic Agents' of the WADA Prohibited List; SARMs were added in 2008. Ostarine is among the most frequently detected SARMs in athlete anti-doping samples and is a common undeclared contaminant in supplements.

Other jurisdictions

No marketing approval in the EU, UK, Australia, or elsewhere. Sold illegally worldwide as a 'research chemical'; frequently mislabeled or adulterated in consumer products.

The bottom line

Ostarine/enobosarm is the SARM with by far the strongest clinical dossier, and that dossier is instructive precisely because it is sobering: across two decades and multiple randomized trials the compound consistently adds DXA lean body mass, yet it has NEVER been approved anywhere and its pivotal Phase 3 muscle-wasting trials (POWER) failed to prove the thing that actually matters to patients — better physical function. Its most credible current prospects (breast cancer, GLP-1 muscle preservation) rest on Phase 2/2b surrogate data still awaiting Phase 3 confirmation. On safety, absence of approval means absence of a fully characterized safety profile, and the harm signals are real, not theoretical: cholestatic liver injury (including cases specifically tied to ostarine), HDL/lipid suppression with FDA-flagged cardiovascular risk, testosterone suppression, and a spectrum of serious adverse-event reports. Consumer products are also routinely mislabeled or adulterated. Bottom line for a reader: this is an unapproved investigational drug and a WADA-banned substance, not a supplement — the lean-mass data are genuine but the functional benefit is unproven and the liver, lipid, and hormonal risks are established enough to take seriously.

References

Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trialThe Lancet Oncology, 2013 (Dobs et al.)
Study Design and Rationale for the Phase 3 Clinical Development Program of Enobosarm (POWER Trials)Current Oncology Reports, 2016 (PMC4853438; PMID 27138015)
GTx Reports Results for Enobosarm POWER Trials for the Prevention and Treatment of Muscle Wasting in Patients with Non-Small Cell Lung Cancer (co-primary physical-function endpoint not met)Fierce Biotech, 2013 (GTx announcement)
Activity and safety of enobosarm in AR+, ER+, HER2- advanced breast cancer (Study G200802): a randomised phase 2 trialThe Lancet Oncology, 2024 (Palmieri et al.; PMID 38342115)
Veru Reports Clinical Data from the Discontinued ARTEST Study of Enobosarm in AR+ ER+ HER2- Metastatic Breast CancerVeru Inc. Investor Relations press release, 2024
Veru Announces Positive Topline Data from Phase 2b QUALITY Study: Enobosarm Preserved Lean Mass in Patients Receiving SemaglutideVeru Inc. Investor Relations press release, 2025
FDA Warns of Use of Selective Androgen Receptor Modulators (SARMs) Among Teens, Young AdultsU.S. FDA Consumer Update, April 2023
Selective androgen receptor modulator use and related adverse events including drug-induced liver injury: analysis of suspected cases (ostarine-specific cholestatic DILI cases; CAERS data)European Journal of Clinical Pharmacology, 2024 (PMC10847181)
Selective Androgen Receptor Modulators (SARMs)-Induced Liver Injury: A Case Report and Review of LiteratureCureus / NCBI, 2022 (PMC8929477)
Substance Profile: What athletes need to know about ostarine (WADA S1 anabolic agent; not approved for human use)U.S. Anti-Doping Agency (USADA)
The Prohibited List (Section S1 Anabolic Agents — SARMs prohibited at all times)World Anti-Doping Agency (WADA)

SARMS Institute Research Desk. Compiled from primary sources. Last updated 20 July 2026.
This review is for education and does not provide medical or legal advice. No SARM is approved for human use.