An independent peptide reference — no sellers, every claim sourced

Anamorelin

Also known as ONO-7643, RC-1291, anamorelin hydrochloride, Adlumiz

Oral ghrelin receptor agonist for cancer cachexia: approved in Japan, refused by the EMA.

clinically proven Growth hormone approved drug

At a glance

Category
Growth hormone
Status
approved drug
Route
oral tablet, taken on an empty stomach
Half-life
approximately 7-12 hours
Onset
Appetite and IGF-1 respond within the first weeks; lean body mass and weight changes are measured over 12 weeks in the trials
Molecular weight
546.7 g/mol (free base); 583.2 g/mol as the hydrochloride
Sequence
Not a conventional peptide. Anamorelin is a small-molecule peptidomimetic ghrelin receptor agonist built on a trimethylglycine-tryptophan-alanine scaffold with an N-methylated backbone

Approved in Japan only — not in the United States. Anamorelin hydrochloride (Adlumiz, Ono Pharmaceutical) was approved on 11 December 2020 by Japan's Ministry of Health, Labour and Welfare, working through the Pharmaceuticals and Medical Devices Agency, for improvement of weight loss and anorexia in cancer cachexia in non-small-cell lung cancer, gastric cancer, pancreatic cancer and colorectal cancer 2; it was launched in Japan in April 2021 5. The European Medicines Agency refused marketing authorisation, the CHMP confirming its negative opinion on re-examination in 2017 34. There is no FDA approval and no approved US indication. Outside Japan it is an investigational compound.

Doping status: Prohibited at all times (WADA S2, growth hormone secretagogues)

Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.

Mechanism of action

Anamorelin is an orally active agonist of the growth hormone secretagogue receptor 1a (GHS-R1a), the ghrelin receptor. It is a peptidomimetic rather than a peptide, which is what gives it oral bioavailability and a half-life long enough for once-daily dosing — the distinguishing property that made it a plausible drug where injectable GHRPs were not.

It reproduces the two main actions of ghrelin. Centrally, GHS-R1a activation in the hypothalamic arcuate nucleus stimulates NPY/AgRP neurons and increases appetite and food intake — the orexigenic effect that patients notice. At the pituitary, GHS-R1a activation on somatotrophs triggers GH release through the Gq/phospholipase C pathway, and simultaneously reduces hypothalamic somatostatin tone. The resulting rise in GH raises hepatic IGF-1, which is anabolic for skeletal muscle.

Cancer cachexia is not simple starvation: it is a syndrome of inflammation-driven catabolism in which muscle is lost through proteasomal degradation regardless of intake, and it does not reverse with nutritional support alone. Anamorelin was designed to attack it from two directions at once — increase intake through the orexigenic pathway, and oppose catabolism through the GH/IGF-1 anabolic pathway. Ghrelin also has some direct anti-inflammatory activity, suppressing TNF-alpha and IL-6, which may contribute.

The regulatory divergence between Japan and Europe turns on whether this mechanism delivers something that matters to the patient. Both regulators saw the same core data: anamorelin reliably increases lean body mass, body weight and appetite, and reliably fails to increase handgrip strength. The Japanese authority judged the gains in weight, appetite and lean mass to be a meaningful benefit in a population with no other approved treatment. The CHMP judged the effect on lean body mass to be marginal, noted the absence of any demonstrated effect on handgrip strength or quality of life, and additionally found — following an inspection of clinical study sites — that safety data had not been adequately recorded 3. On that combination it concluded the benefits did not outweigh the risks. Both positions are defensible readings of the same evidence, and the disagreement is about what counts as clinical benefit in cachexia, not about what the drug does.

What the research shows

The evidence is substantial and unusually well characterised: two large, randomised, double-blind, placebo-controlled phase 3 trials with nearly a thousand patients, published in a major journal, plus supporting Japanese trials. The problem is not the quality of the evidence but its content — the drug consistently hits its body-composition endpoints and consistently misses its function endpoint. That is why two competent regulators reached opposite conclusions.

Research in humans

ROMANA 1 (n=484) and ROMANA 2 (n=495), published by Temel et al. in Lancet Oncology in 2016, randomised patients with inoperable stage III or IV non-small-cell lung cancer and cachexia 2:1 to anamorelin 100 mg daily or placebo for 12 weeks 1. Co-primary endpoints were median change in lean body mass and in handgrip strength. Lean body mass increased significantly versus placebo in both trials, as did body weight and patient-reported appetite and cachexia symptom burden. Handgrip strength did not differ from placebo in either trial 1. ROMANA 3 was a 12-week safety extension. Japanese phase 2 and phase 3 trials (ONO-7643) reproduced the lean body mass and appetite findings in Japanese patients with non-small-cell lung, gastric, pancreatic and colorectal cancer, and formed the basis of the Japanese approval; Wakabayashi et al. describe that regulatory process in detail in the Journal of Cachexia, Sarcopenia and Muscle 2.

Animal and lab research

Rodent models of cancer cachexia showed increased food intake, preserved lean mass and raised IGF-1 with anamorelin, and confirmed GHS-R1a-mediated GH release. The animal work established the dual orexigenic-anabolic rationale but does not address the question the human trials raised, which is whether lean mass gains translate into function.

Caveats. The central limitation is the one the CHMP identified: the trials met a body-composition endpoint but not a functional one, and lean body mass measured by DXA includes water, so part of the gain may not be contractile muscle. Trials ran 12 weeks; there is no long-term efficacy or safety data. There is no demonstrated survival benefit. The EMA inspection finding that safety data were not adequately recorded at study sites is a serious methodological criticism that is independent of the efficacy debate 3. Trials were sponsored by the manufacturer (Helsinn, later Ono in Japan). Efficacy outside the studied tumour types is not established, and use in non-cancer cachexia, sarcopenia or body composition has never been tested.

What it is used for

  • Approved in Japan: improvement of weight loss and anorexia in cancer cachexia in patients with non-small-cell lung cancer, gastric cancer, pancreatic cancer or colorectal cancer 2
  • Refused in the EU: the CHMP declined marketing authorisation and confirmed the refusal on re-examination 34
  • Not approved in the US; no approved indication
  • Investigated but not established: cachexia in other malignancies, and anorexia-cachexia in chronic disease
  • Not studied at all: use for body composition, appetite stimulation or performance in people without cachexia

Dosing

Dose
100 mg once daily orally in the ROMANA trials and in the EU application. The Japanese approved product is a 50 mg tablet; the approved Japanese dose is 100 mg once daily, that is two tablets.
Frequency
once daily
Route
oral, on an empty stomach — the Japanese label specifies dosing at least one hour before a meal, since food substantially reduces absorption
Duration
12 weeks in the pivotal trials, with a 12-week safety extension. In Japanese practice, continuation beyond 12 weeks is assessed on whether the patient is still benefiting; long-term data are limited.
  • The Japanese approved adult dose is 100 mg of anamorelin hydrochloride orally once daily on an empty stomach 2; this is also the dose used in ROMANA 1 and ROMANA 2 1. Anamorelin is a prescription medicine in the only country where it is approved.
  • Food markedly reduces bioavailability; the empty-stomach requirement is not optional 2.
  • The Japanese approval directs that treatment be given under the supervision of a physician with sufficient knowledge and experience in cancer cachexia, and that it be discontinued if no effect is seen after 3 weeks. There is no experience with administration beyond 12 weeks 2.
  • Anamorelin raises blood glucose; hyperglycaemia was the most frequent serious adverse event in the pivotal trials, in 1 patient (under 1 per cent) in ROMANA 1 and 4 patients (1 per cent) in ROMANA 2 1.
  • QT interval prolongation is a recognised cardiac risk with anamorelin and is flagged as a safety consideration in the Japanese approval 2.
  • There is no established dose, duration or safety profile for use outside cancer cachexia. Any protocol circulating for body composition or appetite in healthy people is extrapolation from a cancer trial and has no supporting data.

These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.

Protocols

Adlumiz, cancer cachexia (approved in Japan)

approved product information

Source: Japanese approved product information, as quoted in Journal of Cachexia, Sarcopenia and Muscle, 2021

Daily100 mg orally once daily in the fasting state (the tablet is 50 mg, so two tablets)
At 3 weeksif no effect has been observed, administration should be discontinued
Beyond 12 weeksthe label states there is no experience of administration for longer than 12 weeks

Approved only in Japan, and only for cachexia in non-small-cell lung, gastric, pancreatic and colorectal cancer; the EMA refused the corresponding application. The three-week stop rule is part of the approved schedule rather than a suggestion, and the twelve-week statement is a limit of experience, not a demonstrated safe ceiling.

ROMANA 1 and ROMANA 2 phase 3 trials, non-small-cell lung cancer cachexia

published trial

Source: Temel et al., Lancet Oncology, 2016

Weeks 1-12100 mg orally once daily

These are the trials the approved dose comes from. They met the lean body mass endpoint but not handgrip strength, the co-primary endpoint, which is the divergence behind Japan approving the drug and the EMA refusing it. Nothing in them addresses use for body composition in people without cancer cachexia.

Schedules are reproduced as their source states them. Units, IU and milligrams explains why the figures are not interchangeable between products.

Reconstitution

Storage
Tablets are stored at room temperature in the original packaging, per the product information.

Anamorelin is an oral tablet. There is no injectable form and nothing to reconstitute.

Safety

Side effects

  • Hyperglycaemia and worsening of pre-existing diabetes — hyperglycaemia was the most frequent serious adverse event in the pivotal trials, though there were no differences in grade 3-4 treatment-related adverse events between anamorelin and placebo overall 1
  • QT interval prolongation on ECG — a recognised cardiac risk flagged in the Japanese approval 2
  • Nausea
  • Constipation
  • Dizziness
  • Headache
  • Raised IGF-1 and growth hormone, with the theoretical concerns that follow from elevating growth factors in a cancer population
  • Oedema and fluid retention
  • Fatigue
  • Elevated hepatic transaminases
  • Insomnia
  • Increased appetite — the intended effect, but occasionally troublesome

Do not use if

  • Hypersensitivity to anamorelin, its ingredients or concomitant medications 2
  • Congestive heart failure, recent myocardial infarction, or clinically significant conduction abnormality — the Japanese label restricts use in significant cardiac disease
  • Existing QT prolongation, or concomitant use of QT-prolonging drugs
  • Uncontrolled diabetes mellitus; in controlled diabetes, close glucose monitoring is required
  • Active malignancy is the indication rather than a contraindication here, but the drug raises GH and IGF-1, which are mitogenic. This is an accepted trade-off in palliative cancer cachexia and is not transferable to any other setting
  • Severe hepatic impairment — exposure is increased
  • Pregnancy and breastfeeding: no adequate data
  • Not studied in children

Interactions

Anamorelin is metabolised primarily by CYP3A4. Strong CYP3A4 inhibitors such as ketoconazole, itraconazole, clarithromycin and ritonavir substantially increase exposure and the risk of QT prolongation; strong inducers such as rifampicin, carbamazepine, phenytoin and St John's wort reduce exposure and may abolish the effect. Concomitant QT-prolonging drugs — including many antiemetics, fluoroquinolones, azole antifungals and several cytotoxic agents commonly used in this patient population — should be avoided or the ECG monitored. Anamorelin raises blood glucose, so insulin and oral antidiabetic requirements may increase. Food substantially reduces absorption. Somatostatin analogues antagonise the GH-releasing effect. Concurrent use with other GH secretagogues or with somatropin has not been studied.

Sources