Anamorelin
Also known as: ONO-7643, RC-1291, anamorelin hydrochloride, ghrelin receptor agonist
Oral small-molecule ghrelin receptor agonist (growth hormone secretagogue receptor 1a / GHSR-1a agonist); anticachexia agent
What it is
Anamorelin is an oral prescription pill used by cancer patients who are losing dangerous amounts of weight and muscle — a condition called cachexia. It works by mimicking the hunger hormone ghrelin, stimulating appetite and promoting lean body mass recovery. It is approved in Japan and under investigation globally, primarily for lung, gastric, and pancreatic cancer cachexia.
The scientific side
anamorelin is a synthetic, orally bioavailable small-molecule agonist of the growth hormone secretagogue receptor 1a (GHSR-1a), which is the receptor for the endogenous orexigenic peptide ghrelin. By binding and activating GHSR-1a in hypothalamic neurons, anamorelin mimics ghrelin's physiological actions to produce two principal anabolic effects relevant to cancer cachexia: appetite stimulation and growth hormone (GH) secretion. In the hypothalamus, GHSR-1a activation increases neuropeptide Y and agouti-related peptide signaling while suppressing pro-opiomelanocortin neurons, driving a net increase in food intake and caloric consumption. Concurrently, GHSR-1a activation in the pituitary axis and hypothalamic arcuate nucleus triggers pulsatile GH release, which in turn increases hepatic and peripheral production of insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3). Elevated IGF-1 promotes protein anabolic signaling in skeletal muscle via PI3K/Akt/mTOR pathways, reducing net muscle protein catabolism and supporting lean body mass (LBM) preservation or recovery. Clinical meta-analyses of randomized controlled trials have confirmed these mechanistic predictions: anamorelin 100 mg/day significantly increases total body weight (mean difference approximately +1.56–1.73 kg), lean body mass (mean difference approximately +1.06–1.36 kg), fat mass, IGF-1 (mean increase approximately +51 ng/mL), and IGFBP-3 compared with placebo across multiple cancer types (PMID 37525932, PMID 37709824). Anamorelin also weakly inhibits L-type calcium channel receptors, a property that may contribute to its observed ECG effects including QT interval changes and rare ST-segment abnormalities, via altered cardiac repolarization. Compared with newer GHSR-1a agonists such as KARIs, anamorelin has lower oral bioavailability (approximately 45%) and minimal central nervous system penetrance, which may limit appetite signaling efficacy relative to its peripheral anabolic actions. The clinical consequence of LBM improvement — whether it translates to functional benefits such as handgrip strength or survival — remains an area of active investigation, with the SPIRAL-ANA trial demonstrating that transition from cachexia to a non-cachectic state during anamorelin therapy is associated with significantly improved overall survival.
Class: Oral small-molecule ghrelin receptor agonist (growth hormone secretagogue receptor 1a / GHSR-1a agonist); anticachexia agent
Administration & storage
- Administration
- No injection methods are reported or applicable — anamorelin is an oral medication in all clinical trials and approved formulations
- Storage
- Adlumiz (approved Japanese formulation): store at room temperature, protected from moisture and light per product labeling. Investigational formulations in clinical trials stored per individual trial protocols. No special cold-chain requirements for oral tablet formulation.
- Cautions
- Hyperglycemia is the most clinically important adverse effect; it occurs in approximately 5–35% of patients depending on cancer type and baseline glycemic status, with onset predominantly within the first 28 days of treatment. Blood glucose monitoring is mandatory at baseline and throughout treatment, especially in patients with diabetes, elevated liver enzymes (ALT >42 IU/L), or pancreatic cancer (PMID: 42049364, PMID: 41619712).,QT interval prolongation has been reported with anamorelin. ECG monitoring is recommended before and during treatment, particularly in patients with pre-existing cardiac conditions or those on concomitant QT-prolonging medications.,Reversible ST-T segment changes have been reported in a case of NSCLC; the mechanism may involve weak L-type calcium channel inhibition altering cardiac repolarization. Clinicians should consider ECG monitoring even in the absence of chest symptoms.,Anamorelin stimulates growth hormone secretion via GHSR-1a; use in patients with active or history of hormone-sensitive malignancies (e.g., certain sarcomas with IGF-1 receptor expression) should be evaluated for theoretical tumor-promoting risk, though clinical data do not currently demonstrate a survival detriment.,As an oral compound, drug interactions with CYP enzyme substrates, inducers, or inhibitors should be reviewed. Concomitant corticosteroids and NK1 receptor antagonists (common in oncology) did not significantly increase hyperglycemia risk in one retrospective study, but baseline diabetes remained the strongest predictor.,Anamorelin is not approved for self-administration outside of clinical trial or formal prescription contexts. Off-label compounding and self-injection of anamorelin is not supported by any published evidence and carries unknown risks.
Legal & regulatory status
Anamorelin is not approved by the US FDA. Two pivotal Phase 3 randomized controlled trials (ROMANA 1, NCT01387269; ROMANA 2, NCT01387282) in patients with advanced non-small cell lung cancer and cachexia demonstrated…
Anamorelin is not explicitly listed by name on the current WADA Prohibited List; however, as a growth hormone secretagogue and GHSR-1a agonist that stimulates growth hormone secretion, it falls within the class of…
Anamorelin does not hold a Notice of Compliance from Health Canada and is not approved for sale in Canada as of the reviewed literature. No Health Canada approval has been documented in the peer-reviewed clinical…
What it's studied for
- Cancer cachexia in advanced non-small cell lung cancer (NSCLC) — lean body mass preservation and appetite improvement Phase 3 Randomized Controlled Trial
- Cancer cachexia in unresectable or recurrent gastric cancer — lean body mass and quality of life Phase 2/3 Randomized Controlled Trial
- Cancer cachexia in pancreatic cancer — appetite, lean body mass, and quality of life Prospective Observational / Pilot RCT
- Cancer cachexia in NSCLC during chemoimmunotherapy — cachexia reversal and survival Prospective Multicenter Observational Study
- Cancer cachexia across multiple solid tumor types — systematic review and meta-analysis of body composition and quality of life outcomes Systematic Review / Meta-analysis of RCTs
- Postoperative weight loss and lean body mass preservation following upper gastrointestinal cancer resection Ongoing Phase 3 RCT (Protocol Published)
- Sarcopenia management in gastrointestinal cancers as adjunct to nutritional and exercise interventions Narrative Review / Clinical Expert Guidance
Safety signals
- Hyperglycemia — dose-related insulin resistance
- QT interval prolongation
- ST-T segment changes (reversible) — possible cardiac repolarization effect
- Failure to improve handgrip strength — functional limitation of anabolic effect
- Elevated liver transaminases (ALT/AST) — potential hepatotoxicity signal
- Early treatment discontinuation — tolerability and disease progression
- Hyperglycemia risk amplified in pancreatic cancer — highest reported incidence across cancer types
All studies (8)
Frequently asked
Is anamorelin approved in the United States?
No. Anamorelin is not FDA-approved in the United States. The two pivotal Phase 3 clinical trials (ROMANA 1 and ROMANA 2) demonstrated that anamorelin significantly increased lean body mass in patients with advanced lung cancer and cachexia, but the co-primary endpoint of improving handgrip strength was not met. The FDA has not approved the drug; it remains under clinical investigation in the US. It is approved in Japan for cancer cachexia (lung, gastric, pancreatic, and colorectal cancers).
How does anamorelin help with cancer cachexia?
Anamorelin mimics a natural hunger hormone called ghrelin by activating its receptor (GHSR-1a) in the brain and throughout the body. This produces two key effects: it stimulates appetite and food intake, helping patients eat more, and it triggers the release of growth hormone, which in turn raises IGF-1 levels to support lean muscle tissue building. Clinical trials show it can increase lean body mass by approximately 1 kg over 12 weeks and improve body weight compared with placebo.
What are the main side effects of anamorelin?
The most clinically important side effect is elevated blood sugar (hyperglycemia), occurring in approximately 5–35% of patients depending on cancer type, with pancreatic cancer patients at highest risk. It typically develops within the first four weeks. ECG changes including QT interval prolongation and, rarely, ST-segment changes have also been reported, so baseline and follow-up heart monitoring is recommended. Other potential effects include changes in liver enzymes. Overall, anamorelin was considered well tolerated in clinical trials when patients were appropriately monitored.
Can anamorelin improve survival in cancer patients?
Clinical trials to date have not demonstrated a statistically significant improvement in overall survival with anamorelin compared with placebo. However, the SPIRAL-ANA study found that patients who transitioned from a cachectic to a non-cachectic state on anamorelin during chemoimmunotherapy had significantly longer survival (19.9 vs. 7.1 months). This suggests that reversing cachexia with anamorelin may be associated with survival benefit, but this has not yet been confirmed in a randomized survival trial.
Who should not take anamorelin?
Based on clinical evidence, patients with pre-existing diabetes or high blood sugar levels need very close glucose monitoring and may be at high risk for severe hyperglycemia. Patients with heart conditions or who are taking other medications that affect heart rhythm (QT-prolonging drugs) should have cardiac evaluation before starting anamorelin. Patients with very poor performance status or highly advanced disease may have limited benefit and higher early discontinuation rates. Anamorelin is not approved outside Japan, and outside that country, use is only within formal clinical trials.
Does anamorelin work for types of cancer other than lung cancer?
Anamorelin has been studied beyond lung cancer. A Japanese randomized trial in gastric cancer cachexia showed a trend toward lean body mass improvement, though the primary endpoint was not statistically significant. A prospective observational study in pancreatic cancer found LBM gains in over half of patients, with quality-of-life improvements. Anamorelin is approved in Japan for lung, gastric, pancreatic, and colorectal cancer cachexia. Ongoing trials are investigating its use in postoperative upper GI cancer settings.