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Anamorelin

An oral ghrelin-receptor agonist approved in Japan for cancer cachexia, which reliably increases appetite, body weight and lean mass but has never shown a matching improvement in strength or survival.

Also known as Anamorelin hydrochloride, Oral ghrelin mimetic, Adlumiz, ONO-7643, RC-1291, ANAM

Approved drug — Licensed by a major regulator for human use, with phase-3 trial data behind it.

Approved in Japan in 2021 for cachexia in non-small-cell lung, gastric, pancreatic and colorectal cancer, supported by the ROMANA 1 and 2 phase 3 trials showing consistent lean body mass and weight gain. The failure of the handgrip strength co-primary endpoint is important and honest: it adds mass, but the functional benefit was not demonstrated, and both the FDA and EMA declined approval on that basis.

How it works

Anamorelin mimics ghrelin at GHS-R1a in both the pituitary and the hypothalamic arcuate nucleus, so it simultaneously raises GH and IGF-1 and activates NPY/AgRP appetite circuitry. In cancer cachexia that combination is exactly what is wanted: cachexia is driven by inflammatory catabolism and anorexia together, and anamorelin addresses the anorexia while the GH/IGF-1 arm supports lean tissue. The ROMANA phase 3 programme in non-small-cell lung cancer confirmed significant gains in lean body mass and body weight over 12 weeks, but handgrip strength - the co-primary endpoint - did not improve, which is why the FDA declined approval while Japan approved it. It has a modest anti-inflammatory effect on IL-6 and TNF-alpha in some analyses.

Targets: GHS-R1a (ghrelin receptor), Arcuate NPY/AgRP neurons, Pituitary somatotrophs, IGF-1 axis

Dosing

ProtocolDoseFrequencyRoute
Cancer cachexia (Japanese label)In the morning on an empty stomach, at least one hour before food.100 mgonce dailyoral
  • · 100 mg once daily. Fasted administration matters - food substantially reduces absorption.

Titration

No titration - the dose is fixed at 100 mg daily.

Cycling

In the approved indication it is continued while cachexia persists and the patient is benefiting. Japanese label guidance limits initial evaluation to 12 weeks, reassessing whether to continue.

Work out your exact syringe units →

Pharmacology

Half-life
Roughly 7 hours, supporting once-daily dosing.
Onset
Appetite improves within days; measurable lean body mass and weight gain by 3 to 4 weeks and continuing over 12 weeks.
Routes
oral
Molecule
Non-peptide small-molecule GHS-R1a agonist
Molecular weight
546.7 Da

Handling

Diluent
Not applicable - oral tablet
Lyophilised
Not applicable. Store tablets at room temperature in the original packaging.
Reconstituted
Not applicable.

Mixing

Supplied as 50 mg tablets in Japan; two tablets once daily.

Side effects

  • very commonIncreased appetite— The intended effect in this population.
  • commonHyperglycaemia and elevated HbA1c— The most clinically relevant adverse effect; the Japanese label requires glucose monitoring.
  • commonNausea
  • uncommonElevated hepatic transaminases
  • uncommonPeripheral oedema
  • uncommonECG changes including conduction disturbance— Reported in post-marketing surveillance.
  • uncommonDizziness

Do not use if

  • Congestive heart failure, myocardial infarction or angina - listed as contraindications in the Japanese label.
  • Concomitant use with strong CYP3A4 inhibitors such as clarithromycin or itraconazole.
  • Poorly controlled diabetes, given the hyperglycaemia signal.
  • Pregnancy.
  • Known hypersensitivity.

Combining it

  • conflictStrong CYP3A4 inhibitors — Substantially raise anamorelin exposure; contraindicated in the Japanese label.
  • cautionStrong CYP3A4 inducers — Reduce exposure and may render treatment ineffective.
  • cautioninsulin — Hyperglycaemia is common; insulin and oral agent doses may need increasing.
  • redundantmk-677 — Same receptor, same pharmacology, same appetite and glucose effects.
  • cautionQT-prolonging medicines — Conduction abnormalities have been reported.

What to monitor

  • · Fasting glucose and HbA1c at baseline and regularly - a labelled requirement.
  • · Liver function tests.
  • · ECG in patients with cardiac risk factors.
  • · Body weight and lean body mass as the efficacy measure; handgrip strength if function is the goal.

Legal status

Approved and marketed in Japan as Adlumiz. Not approved in the US or EU - the FDA and EMA both declined. Prohibited in sport under WADA S2.

References

  • Temel et al. 2016 Lancet Oncology, ROMANA 1 and ROMANA 2 phase 3 anamorelin trials in NSCLC cachexia (trial)
  • Wakabayashi et al. 2021, regulatory approval of anamorelin for cancer cachexia in Japan (review)

Mechanism in depth

Anamorelin is the most instructive compound in this class for anyone trying to think clearly about what ghrelin-receptor agonism actually buys you, because it is the only one whose therapeutic claim was tested against a functional endpoint in a proper phase 3 programme - and that endpoint failed. Cancer cachexia is driven by two things running together: inflammatory catabolism, mediated by IL-6, TNF-alpha and related signalling, and anorexia. Anamorelin addresses the anorexia arm through arcuate NPY/AgRP activation and supports lean tissue through the GH/IGF-1 arm, and both of those work. ROMANA 1 and ROMANA 2, two randomised double-blind phase 3 trials in non-small-cell lung cancer cachexia, showed consistent, significant gains in lean body mass and body weight over 12 weeks. Handgrip strength was a co-primary endpoint and it did not improve. That result is the single most useful data point in the entire growth hormone secretagogue field, because it is the same finding as Nass's two-year MK-677 trial in healthy older adults: mass without function. Two independent programmes, different compounds, different populations, different sponsors, same dissociation. The reasonable inference is that GHS-R1a agonism reliably adds tissue mass - some of it water, some of it real - and does not reliably add contractile capacity, and anyone taking any compound in this class for strength should sit with that. The FDA and EMA both declined approval on exactly that basis; Japan approved it in 2021 on the mass and weight gain, which is a defensible position in a palliative population where weight loss itself is distressing and prognostically bad. Hyperglycaemia is the main labelled adverse effect and glucose monitoring is required.

What usually goes wrong

Taking it with food, which substantially reduces absorption and is the most common practical error with the fasted-morning requirement. Beyond that, the compound's problem is not that it fails - it does what it claims, reliably - but that what it claims turned out not to be what patients needed. Two regulators looked at significant weight and lean mass gain without functional improvement and declined to approve. Anyone reaching for anamorelin, or for MK-677, on the theory that added lean mass means added capability should understand that this specific question was asked in a properly powered phase 3 programme and answered no. The cardiac contraindications are also genuine: heart failure, recent myocardial infarction and angina are listed contraindications rather than cautions, which is a stronger statement than most labels make.

Titration ladder

  1. 100 mgJapanese label, fixed dose — 100 mg once daily as two 50 mg tablets, in the morning on an empty stomach at least one hour before food. There is no titration - the dose is fixed. Fasted administration is not optional; food substantially reduces absorption.

Bloodwork worth running

MarkerWhenWhy it matters
Fasting glucose and HbA1cBaseline and regularly throughout treatment.Hyperglycaemia is the most clinically relevant adverse effect and monitoring is a labelled requirement in Japan. It is the same glycaemic liability that runs through every sustained GHS-R1a agonist.Act if: A rise into the diabetic range, or worsening control in an existing diabetic, prompts a treatment review. Poorly controlled diabetes is a contraindication.
ALT, AST and bilirubinBaseline and periodically.Elevated hepatic transaminases are a recognised adverse effect.Act if: Significant transaminase elevation prompts discontinuation.
ECGBaseline in patients with cardiac risk factors.Conduction disturbances reported in post-marketing surveillance, and cardiac disease is a labelled contraindication.Act if: Existing heart failure, recent myocardial infarction or angina means do not use.
Body weight and lean body massBaseline and at 12 weeks, which is the initial evaluation window in the Japanese label.The efficacy measure, and the one that will move.Act if: No weight or lean mass gain at 12 weeks prompts a decision about whether to continue.
Handgrip strengthBaseline and 12 weeks, with a calibrated dynamometer.Included deliberately, because this is the endpoint the phase 3 programme failed. If function is what you actually care about, measure it rather than inferring it from the scale.Act if: No specific action - this is an expectation-setting measurement, and the honest expectation is that it will not improve.

Pharmacokinetics

Crosses blood-brain barrier
partial
Metabolism
CYP3A4. Strong inhibitors such as clarithromycin and itraconazole substantially raise exposure and are contraindicated in the Japanese label; strong inducers reduce exposure enough to render treatment ineffective.
Elimination
Not characterised in the sources resolved here.

Receptor targets

  • GHS-R1a (ghrelin receptor), pituitary somatotroph — Orally active full agonist; specific Ki not resolved here

    GH and IGF-1 elevation supporting lean tissue accrual.

  • GHS-R1a, arcuate NPY/AgRP neurons — Not separately quantified

    Appetite stimulation - the intended therapeutic effect in cachexia rather than a side effect.

  • Inflammatory cytokines IL-6 and TNF-alpha — Not applicable

    A modest anti-inflammatory effect has been reported in some analyses. This is a secondary observation, not an established mechanism.

  • CYP3A4 (substrate) — Major metabolic pathway

    Strong inhibitors are contraindicated in the Japanese label; strong inducers can render treatment ineffective.

  • Cardiac conduction — Not applicable

    ECG changes including conduction disturbance reported in post-marketing surveillance. Congestive heart failure, myocardial infarction and angina are listed contraindications in the Japanese label - the same cardiac signal that appeared in the MK-677 hip-fracture programme.

Trials

  • ROMANA 1 and ROMANA 2 - Temel et al., anamorelin in patients with non-small-cell lung cancer and cachexia 3 · 12 weeks · 2016

    Co-primary endpoints of lean body mass and handgrip strength over 12 weeks. Lean body mass and body weight increased significantly; handgrip strength did not improve. This dissociation is why the FDA and EMA declined approval and why Japan's approval is based on the mass endpoint alone.

  • Laird et al., pooled reanalysis of anamorelin efficacy in NSCLC cachexia from ROMANA 1 and ROMANA 2 3 analysis · 12 weeks · 2025

    Further insights into which patients responded and on what endpoints, published nine years after the original trials.

What to expect, and when

Appetite improves within days. Measurable weight and lean body mass gain appear by three to four weeks and continue over the 12 weeks the trials ran. The Japanese label sets an initial evaluation at 12 weeks to decide whether to continue. Hyperglycaemia develops gradually and is the reason for ongoing rather than one-off glucose monitoring.

Stacking and comparisons

In its approved indication anamorelin is used alone alongside standard cachexia care. Anything else at GHS-R1a - MK-677, ipamorelin, GHRP-2, GHRP-6, ghrelin itself - is redundant. The interactions that matter are CYP3A4-mediated and they matter a great deal: strong inhibitors such as clarithromycin and itraconazole are contraindicated in the Japanese label, and strong inducers can render treatment ineffective. In an oncology population on multiple concurrent drugs, that is not a footnote. Insulin and oral hypoglycaemic requirements may rise given the hyperglycaemia signal, and QT-prolonging medicines warrant caution given the reported conduction abnormalities.

Against MK-677: the same pharmacology, approved in one country for one indication, with a proper phase 3 programme behind it rather than a single two-year trial - and the two programmes found the same thing. If you want to know what chronic oral GHS-R1a agonism does to a human, ROMANA and Nass together are the answer, and they agree. Against megestrol acetate and corticosteroids for cachexia: those increase appetite and weight but with fat rather than lean mass gain and with their own harms; anamorelin's lean mass selectivity is a genuine advantage in that comparison. Against exercise and nutritional support: the trials were not designed to answer that, and in cachexia neither is usually sufficient alone. Against the whole GHS-R1a class for body composition in healthy people: anamorelin's failed handgrip endpoint is the most honest available answer to the question everyone in this class is really asking.

Rough cost

$300–$700/month. Japanese pricing for Adlumiz at 100 mg daily, converted approximately. It is not marketed in the US or EU and there is no legitimate route to it outside Japan. Figures are rough and currency-dependent.

Genuinely uncertain

  • The Japanese label was not retrieved directly, so no pharmacokinetic figures - half-life, tmax, volume of distribution, clearance, food-effect magnitude - are asserted here. The Core record's 7-hour half-life is not verified.
  • The participant numbers, effect sizes and confidence intervals from ROMANA 1 and ROMANA 2 were not extracted from the primary publication in this session.
  • The anti-inflammatory effect on IL-6 and TNF-alpha is described in secondary analyses and was not verified.
  • There is no data on use in non-cachectic populations, which is the only way anyone outside oncology would use it.
  • The 2021 Japanese approval date and the specific approved tumour types were not independently reverified here.
  • Why lean body mass increased without a matching strength gain is not explained by the trials. Fluid, non-contractile tissue and the underlying disease process are all candidates.

Papers