Anamorelin
An oral ghrelin mimetic that reliably adds lean mass in cancer cachexia and just as reliably fails to add strength
Anamorelin is taken by mouth, activates the ghrelin receptor, and raises lean mass, weight and appetite in cancer cachexia. Handgrip strength did not follow. Japan approved it; the US has not.
What is it?
Cachexia is not simple weight loss: people with advanced cancer lose muscle and fat, eat less and lose function, and no US-approved drug reverses it. Ghrelin is the obvious lever but must be injected; anamorelin is a small molecule at the same receptor that works by mouth.
The effect on body composition is consistent. In ROMANA 1 and ROMANA 2, two phase 3 trials in advanced lung cancer with cachexia, 100 mg daily increased lean body mass against placebo in both. A Japanese phase 3 trial in 174 patients found the same, 1.38 kg gained against 0.17 kg lost over 12 weeks.
Pooled ROMANA data suggest the gain depends on who is treated. Across 795 patients, weight and lean mass rose in every inflammation group, and only in the most inflamed did grip strength and appetite scores also improve. Outside lung cancer the picture is mixed: a 203-patient gastric cancer trial saw lean mass rise 0.99 kg against 0.14 kg without reaching significance, and a small urothelial cancer trial found no difference in nutrition markers or muscle.
What did not move was strength: handgrip strength was a co-primary endpoint in all three phase 3 trials, and anamorelin never beat placebo. Pairing it with exercise is one response: patients who combined anamorelin with resistance and aerobic training gained weight, muscle and grip strength over 12 weeks.
The safety signals are metabolic and cardiac. Hyperglycaemia affected 29.5% of patients in one real-world series, and growth hormone stimulation is the suspected cause. In Japan's adverse-event database, conduction defects had a reporting odds ratio of 20 for anamorelin, with a median onset of 13 days, and all seven published case reports describe recovery. Healthy volunteers gained weight within days, and a case report describes refractory ventricular tachycardia attributed to the drug.
Mechanism of Action
Anamorelin is an oral small molecule that activates the ghrelin receptor, the same receptor the appetite hormone ghrelin uses.
Appetite
Ghrelin receptor activation increases appetite, and trials recorded better anorexia scores alongside weight gain.
Growth hormone and IGF-1
It stimulates growth hormone release; IGF-1 rose within a week in a randomised trial, and higher IGF-1 tracked with muscle gain.
Side effects follow the hormones
Growth hormone stimulation is the suspected cause of hyperglycaemia; conduction defects are a separate cardiac signal, usually in the first weeks.
Published Research
These are the trials that describe anamorelin, read from their PubMed abstracts: the phase 3 programme and two Japanese trials.
ROMANA 1 and ROMANA 2
Two randomised double-blind phase 3 trials at 93 sites in 19 countries gave 100 mg daily or placebo in stage III or IV lung cancer with cachexia. Over 12 weeks lean mass rose; handgrip strength, the co-primary endpoint, did not.
Japanese phase 3
174 patients with unresectable lung cancer and cachexia took 100 mg daily or placebo for 12 weeks. Lean body mass rose 1.38 kg against a 0.17 kg fall, with weight and anorexia improving; handgrip strength did not.
The dose-finding phase 2
181 Japanese patients took 50 mg, 100 mg or placebo for 12 weeks. Lean mass rose 1.15 kg on 100 mg against 0.55 kg on placebo and weight 1.77 kg against a 0.93 kg loss; grip strength again showed no effect.
SPIRAL-ANA: with chemoimmunotherapy
In 114 patients with lung cancer cachexia on chemoimmunotherapy plus anamorelin, 71.8% of those assessed at week 12 were no longer cachectic; there was no control arm and the survival target was missed.
Hyperglycaemia in practice
In 129 patients in routine care, 29.5% developed hyperglycaemia, mostly within 28 days; diabetes and raised ALT predicted it.
ROMANA: who gains most
Pooling 795 patients from ROMANA 1 and 2, anamorelin raised weight, lean mass and fat mass in every inflammation-score group; in the most inflamed (mGPS 2) it also improved handgrip strength and the anorexia/cachexia subscale, and patients with 10% or more prior weight loss gained the most lean mass.
Gastric cancer RCT
In an open-label trial at 10 Japanese hospitals, 203 patients with gastric cancer cachexia on chemotherapy were randomised to 100 mg daily or no anamorelin. At 8 weeks lean mass rose 0.99 kg against 0.14 kg, a difference that missed significance (P = 0.063); 5 patients on anamorelin developed hyperglycaemia.
Urothelial cancer RCT
In 38 patients with metastatic urothelial cancer on platinum chemotherapy randomised to anamorelin or control, prealbumin (the primary endpoint), albumin, weight and skeletal muscle index changed similarly; IGF-1 was higher on anamorelin after 1 week.
Pancreatic cancer, prospective
In 17 evaluable patients, lean mass rose 0.9 kg at 1 month and 1.4 kg at 2 months, and appetite and quality-of-life scores improved; the 10 responders gained 3.4 kg of lean mass and improved grip strength by 2 months.
Pancreatic cancer, real world
Of 45 patients with inoperable or relapsed pancreatic cancer, 31 stayed on anamorelin for 1 month and 20 for 4 months; at 1 month appetite, weight (+1.8 kg) and muscle (+0.9 kg) had risen, and responders lived longer than non-responders (366 against 106 days).
With rehabilitation
Patients given anamorelin with outpatient resistance and aerobic training gained weight (48.8 to 53.7 kg), skeletal muscle and grip strength over 12 weeks; those with a worse performance status were less likely to stay on the drug.
Kidney function
In a propensity-matched study of cancer cachexia, anamorelin users had larger improvements in creatinine and eGFR over 8 weeks and a lower risk of renal decline; the early improvement drifted back toward baseline.
Conduction defects
A literature review found seven cases of conduction defects, all within about three weeks of starting and all recovering; in Japan's adverse-event database the reporting odds ratio was 20.0, with a median onset of 13 days.
Reversible ST changes
A case report describes ST elevation five days after starting anamorelin, without chest pain or enzyme rise, that normalised by day 19 after the drug was stopped.
Very wide QRS tachycardia
A case report describes an extremely wide QRS tachycardia on anamorelin that normalised after the drug was stopped; the authors stress ECG monitoring, especially in patients with liver impairment.
Type 1 diabetes
In a woman with type 1 diabetes, blood glucose and growth hormone rose four days after starting anamorelin, which the authors attribute to growth hormone stimulation.
Dosing Data
There is no US label. The phase 3 trials gave 100 mg by mouth once daily for 12 weeks; a phase 2 trial also tested 50 mg.
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Side Effects & Contraindications
Reported Side Effects
From the trials above and the published case reports.
Contraindications & Cautions
Approved in Japan for cancer cachexia; not approved in the US.
Legal Status
Anamorelin is approved in Japan and nowhere else.
Frequently Asked Questions
?What is anamorelin?
An oral ghrelin receptor agonist: a small molecule, not a peptide, so it survives being swallowed.
?Does it work?
On body composition, yes: lean mass, weight and appetite rose in every phase 3 trial. On strength, no.
?Why Japan but not the US?
Japan approved it in 2021 on its lean-mass results. No US approval has followed; Helsinn ran two more phase 3 trials that finished in 2023.
?Is it a muscle-building drug?
Not on this evidence: the mass it added in cancer patients did not show up as strength.
?Does anamorelin affect the heart?
Conduction defects have a reporting odds ratio of 20 in Japan's adverse-event database, with a median onset of 13 days, and case reports describe ST changes and a very wide QRS tachycardia that resolved after stopping. Reviewers suggest ECG checks in the first weeks.
?Does it raise blood sugar?
Yes. In 129 patients in routine care, 29.5% developed hyperglycaemia, mostly within 28 days, with diabetes and raised ALT as predictors. Growth hormone stimulation is the suspected reason.
References
- [pubmed] Temel JS, et al. "Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials." Lancet Oncol, 2016;17(4):519-531. PMID: 26906526.
- [pubmed] Katakami N, et al. "Anamorelin (ONO-7643) for the treatment of patients with non-small cell lung cancer and cachexia: Results from a randomized, double-blind, placebo-controlled, multicenter study of Japanese patients (ONO-7643-04)." Cancer, 2018;124(3):606-616. PMID: 29205286.
- [pubmed] Takayama K, et al. "Anamorelin (ONO-7643) in Japanese patients with non-small cell lung cancer and cachexia: results of a randomized phase 2 trial." Support Care Cancer, 2016;24(8):3495-505. PMID: 27005463.
- [pubmed] Garcia JM, et al. "Pharmacodynamic hormonal effects of anamorelin, a novel oral ghrelin mimetic and growth hormone secretagogue in healthy volunteers." Growth Horm IGF Res, 2009;19(3):267-73. PMID: 19196529.
- [pubmed] Naito T, et al. "A multicenter, open-label, single-arm study of anamorelin (ONO-7643) in patients with cancer cachexia and low body mass index." Cancer, 2022;128(10):2025-2035. PMID: 35195274.
- [pubmed] Garcia JM, et al. "Effect on body weight and safety of RC-1291, a novel, orally available ghrelin mimetic and growth hormone secretagogue: results of a phase I, randomized, placebo-controlled, multiple-dose study in healthy volunteers." Oncologist, 2007;12(5):594-600. PMID: 17522248.
- [pubmed] Leese PT, et al. "An open-label clinical trial of the effects of age and gender on the pharmacodynamics, pharmacokinetics and safety of the ghrelin receptor agonist anamorelin." Clin Pharmacol Drug Dev, 2015;4(2):112-120. PMID: 26640742.
- [other] US FDA, Drugs@FDA (openFDA): no application for anamorelin. Read September 30, 2026.
- [other] Ono Pharmaceutical, press release, January 22, 2021: Japanese approval of Adlumiz (anamorelin) for cancer cachexia. Read September 30, 2026.
- [clinicaltrials] ClinicalTrials.gov NCT03743064 and NCT03743051: Helsinn's two phase 3 trials in lung cancer, 318 participants each, completed 2022 and 2023. Read September 30, 2026.
- [pubmed] Morimoto K, et al. "A Prospective Observational Study of Anamorelin During Chemoimmunotherapy in Non-Small Cell Lung Cancer With Cachexia (SPIRAL-ANA)." J Cachexia Sarcopenia Muscle, 2026;17(4):e70340. PMID: 42411631.
- [pubmed] Amakawa Y, et al. "Timing and Risk Factors for Hyperglycemia Associated With Anamorelin Administration." Anticancer Res, 2026;46(5):2725-2733. PMID: 42049364.
- [pubmed] Laird BJA, et al. "Anamorelin Efficacy in Non-Small-Cell Lung Cancer Patients With Cachexia: Insights From ROMANA 1 and ROMANA 2." J Cachexia Sarcopenia Muscle, 2025;16(1):e13732. PMID: 39992021.
- [pubmed] Yamamoto K, et al. "Efficacy and safety of anamorelin for cancer cachexia in patients with unresectable or recurrent gastric cancer: a multicentre, open-label, randomised controlled trial." EClinicalMedicine, 2025;88:103500. PMID: 41181834.
- [pubmed] Odagiri K, et al. "Efficacy and safety of anamorelin in patients with metastatic urothelial carcinoma receiving systemic chemotherapy: a randomized controlled study." Oncologist, 2025;30(7). PMID: 40592718.
- [pubmed] Matsukane R, et al. "Prospective study of anamorelin in pancreatic cancer cachexia: Clinical and translational insights into response heterogeneity." Clin Nutr, 2026;58:106581. PMID: 41619712.
- [pubmed] Yamaguchi A, et al. "Real-world effectiveness of anamorelin in patients with unresectable and relapse pancreatic cancer: a prospective observational study." J Gastrointest Oncol, 2025;16(3):1268-1279. PMID: 40672072.
- [pubmed] Hasegawa M, et al. "Impact of the Combination of Anamorelin and Rehabilitation on Functional and Nutritional Outcomes in Patients with Cancer Cachexia." Nutr Cancer, 2025;77(1):86-92. PMID: 39207261.
- [pubmed] Sato A, et al. "Association between anamorelin therapy and renal function in patients with cancer cachexia: a propensity score-matched retrospective study." Eur J Clin Pharmacol, 2026;82(7). PMID: 42298206.
- [pubmed] Yabuki N, et al. "Anamorelin and Conduction Defects: A Literature Review and Analysis of the Japanese Pharmacovigilance Database." In Vivo, 2025;39(1):404-410. PMID: 39740881.
- [pubmed] Akaishi H, et al. "Reversible ST-T Segment Changes Induced by Anamorelin: A Case Report." Respirol Case Rep, 2025;13(11):e70398. PMID: 41211336.
- [pubmed] Shimojo K, et al. "An extremely wide QRS complex tachycardia induced by anamorelin." J Arrhythm, 2024;40(4):1022-1025. PMID: 39139904.
- [pubmed] Okuro K, et al. "Anamorelin Induced Hyperglycemia in a Patient with Type 1 Diabetes by Stimulating Growth Hormone Secretion." Intern Med, 2025;64(17):2592-2596. PMID: 39993750.
Sources & Citations
Studies were read from their PubMed abstracts; DailyMed has no anamorelin label. Read October 7, 2026.
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