PwPepwise

Anamorelin

Growth Hormone

a.k.a. Adlumiz

Oral ghrelin agonist

Anamorelin is an oral medication that mimics ghrelin, a natural hormone produced in the stomach that stimulates hunger and promotes muscle growth.

§Dosing at a glance

2 protocols · from the research
What it's forDoseHow oftenHowFor how long
50 mg once-daily oral dose100 mg—OralTaken by mouth.—
24 weeks100 mgOnce dailyOralTaken by mouth.—

Approximate values pulled from the research — double-check before dosing.

§01Summary

Anamorelin is an oral medication that mimics ghrelin, a natural hormone produced in the stomach that stimulates hunger and promotes muscle growth. By activating the same receptor as ghrelin, anamorelin signals the body to increase appetite, build lean tissue, and release growth hormone — making it a targeted approach for people experiencing severe unintentional weight loss and muscle wasting associated with cancer, a condition known as cancer cachexia.

In patients with advanced non-small cell lung cancer (NSCLC) and cachexia, anamorelin consistently increases lean body mass and total body weight compared to placebo1,2,3. Multiple large randomized trials and meta-analyses confirm these body composition benefits, with patients gaining approximately 1–1.8 kg of lean mass over 12 weeks1,4,5. Quality of life and anorexia-related symptoms also appear to improve with treatment2,3,15. Anamorelin is generally well tolerated, with a safety profile comparable to placebo in large trials1,15. The drug is approved in Japan for cancer cachexia and has been studied across multiple cancer types, with research in gastric cancer and pancreatic cancer actively developing19,14.

This is the layperson summary. Mechanism, dosing, the evidence base, and the published literature are in the sections below — every claim links to its source.

§02In depth

Anamorelin (ONO-7643) is a selective, orally bioavailable small-molecule agonist of the growth hormone secretagogue receptor type 1a (GHSR-1a), the endogenous receptor for the appetite-regulating and anabolic hormone ghrelin. By directly activating GHSR-1a, anamorelin mimics ghrelin's dual physiological role: stimulating the anterior pituitary to release growth hormone (GH) and acting centrally to promote appetite and energy intake9,20.

Upon oral administration, anamorelin produces significant, dose-dependent increases in circulating GH levels, followed by sustained elevations in insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 (IGFBP-3) over days of treatment9. Changes in body weight correlate directly with IGF-1 changes, identifying the GH/IGF-1 somatotropic axis as the primary mediator of anamorelin's anabolic effects on body composition9. This axis drives protein synthesis and lean tissue accrual, explaining the consistently observed increases in lean body mass and fat mass in clinical trials1,3,4,17. Meta-analytic data confirm significant increases in circulating IGF-1 (weighted mean difference +51.16 ng/mL) and IGFBP-3 (+0.43 µg/mL) with anamorelin treatment versus placebo17.

Anamorelin demonstrates selective activity at the somatotropic axis. At therapeutic doses, effects on other anterior pituitary hormone axes — including gonadotropic (LH, FSH), corticotropic (ACTH), and thyrotropic (TSH) axes — are negligible, with mean hormone levels remaining within normal ranges9. Prolactin is similarly unaffected at standard doses. This selectivity distinguishes anamorelin from broader endocrine stimulants and contributes to its favorable tolerability profile.

A notable metabolic consideration is that GHSR-1a activation can attenuate insulin sensitivity. In healthy volunteers, a dose-dependent increase in insulin resistance (HOMA-IR) was observed at 75 mg/day but not at 25 or 50 mg/day doses9. In cancer patients receiving the clinical 100 mg/day dose, hyperglycemia is the primary metabolic adverse event, occurring at low frequency across large trials1,2. Pharmacodynamic studies confirm that the body weight gains observed with anamorelin are accompanied by broad anabolic activity affecting both lean and fat compartments, with improvements in nutritional biomarkers such as prealbumin also reported3,16. The dissociation between lean mass accrual and functional muscle strength outcomes observed across trials suggests that skeletal muscle protein accretion via the GH/IGF-1 axis may be incomplete or context-dependent in advanced cancer, potentially reflecting the multifactorial nature of cancer-associated muscle dysfunction beyond the anabolic deficit alone1,3,4.

§04Evidence & efficacy

Evidence base
214Studies
121Human
4Animal

Anamorelin consistently increases lean body mass (LBM) and total body weight in patients with advanced NSCLC and cancer cachexia. In both ROMANA 1 and ROMANA 2, anamorelin produced median LBM increases of +0.99 kg and +0.65 kg respectively, compared to decreases of -0.47 kg and -0.98 kg in placebo groups (p<0.0001 for both)1. A Japanese phase 3 RCT confirmed these findings, with anamorelin producing a least squares mean LBM increase of +1.38 kg versus -0.17 kg for placebo (p<0.0001)3. Meta-analyses pooling multiple RCTs report a mean LBM increase of approximately +1.06–1.36 kg and total body weight increase of approximately +1.56–1.78 kg over placebo4,5,17.

Anamorelin also improves anorexia-related symptoms and quality of life in NSCLC cachexia patients2,3,15. Anorexia-cachexia symptom burden, assessed by validated scales, is significantly reduced versus placebo2,15,16. IGF-1 and IGFBP-3 levels increase significantly with treatment, reflecting robust somatotropic axis activation9,16,17. At the 100 mg dose, appetite improvement has been reported in meta-analytic subgroup analyses17.

In a post hoc analysis of ROMANA 1 and 2, patients with the highest systemic inflammation (mGPS=2), BMI below 20 kg/m², or weight loss ≥10% may derive amplified body composition and symptomatic benefit from anamorelin10.

In a gastric cancer RCT, anamorelin produced a numerically greater LBM increase (+0.99 kg vs +0.14 kg) compared to control, though the primary endpoint narrowly missed statistical significance19. Anamorelin's efficacy in pancreatic cancer is being investigated in an active registered trial14. No significant overall survival benefit has been demonstrated in NSCLC trials2,4,5.

§05Safety

Anamorelin has a well-characterized tolerability profile across multiple large randomized controlled trials. In the pivotal ROMANA 1 and ROMANA 2 phase 3 trials, the frequency of grade 3–4 treatment-related adverse events was not significantly different between anamorelin and placebo groups1. The most notable adverse event was hyperglycemia, occurring in fewer than 1% of anamorelin-treated patients in ROMANA 1 and approximately 1% in ROMANA 21. Across phase 2 and phase 3 data, hyperglycemia and diabetes were each reported in 5% or fewer of patients2. In the ROMANA 3 safety extension study covering up to 24 weeks, treatment-emergent adverse events occurred in 52.2% of anamorelin patients versus 55.7% of placebo patients, with grade ≥3 events in 22.4% versus 21.6%, and no drug-related deaths reported15.

In a small crossover pilot study, hyperglycemia (n=2), nausea (n=1), and dizziness (n=1) were reported as possibly or probably related to anamorelin, all mild in severity20. In phase 2 integrated analysis, grade 3–4 events including fatigue, asthenia, atrial fibrillation, and dyspnea each occurred in approximately 5% of anamorelin-treated patients, though the advanced cancer population confounds attribution7. In healthy volunteer pharmacodynamic studies, a dose-dependent insulin resistance signal (elevated HOMA-IR) was observed at 75 mg but not at 25 or 50 mg doses9.

Meta-analytic data confirm no statistically significant difference in overall adverse event rates or serious adverse events between anamorelin and placebo across seven RCTs5,4. In the gastric cancer RCT, hyperglycemia was the primary adverse event of note, with grade 1–2 in 4% and grade 3 in 1% of anamorelin-treated patients19.

§06History

Anamorelin (development code ONO-7643; also known as RC-1291) was developed as a synthetic, orally active small-molecule ghrelin receptor agonist, building on the discovery of growth hormone secretagogue receptors and the characterization of ghrelin as an endogenous ligand in the late 1990s. The compound was designed to address the unmet need in cancer cachexia — a debilitating syndrome of involuntary weight and muscle loss affecting a substantial proportion of cancer patients — by harnessing the appetite-stimulating and anabolic properties of the ghrelin signaling axis in a convenient oral formulation.

Early phase 1 and pharmacodynamic work in healthy volunteers established anamorelin's mechanism of action, confirming dose-dependent GH release, sustained IGF-1 elevation, and selective somatotropic axis activation at doses of 25–75 mg daily9. A crossover pilot study in cancer patients demonstrated proof-of-concept for weight gain and appetite improvement with 50 mg dosing20. Integrated phase 2 RCT data in cancer cachexia patients provided initial evidence of lean body mass benefit, supporting advancement to phase 37.

The pivotal phase 3 program — ROMANA 1 and ROMANA 2 — conducted in patients with advanced NSCLC and cachexia, was published in The Lancet Oncology in 2016 and established anamorelin's efficacy for lean body mass and body weight improvement1. The ROMANA 3 safety extension further characterized the long-term tolerability profile15. A Japanese phase 3 trial (ONO-7643-04) replicated these findings in an Asian population3, supporting regulatory approval in Japan for cancer cachexia. Regulatory review in Western markets was complicated by the failure to improve handgrip strength in the pivotal trials1. Research is actively expanding into gastric cancer19 and pancreatic cancer14, with multiple registered trials currently underway.

§07References