Peptides›GH secretagogue, Metabolic›Anamorelin

Anamorelin

/ Non-peptide ghrelin receptor (GHS-R1a) agonist (small molecule)

TIER 2 · TranslationalN = 0 · TESTING PENDINGMW 556.70 g·mol⁻¹

ALIAS · ONO-7643 · Adlumiz (trade — Japan) · Anamorelin hydrochloride · RC-1291

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Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

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§ A · Identity

Primary sequence— sequence not captured —

MW · 556.70CLASS · Non-peptide ghrelin receptor (GHS-R1a) agonist (small molecule)CATEGORY · GH secretagogue, Metabolic

Phase 3 RCTs (ROMANA-1, ROMANA-2, ROMANA-3) in non-small-cell lung cancer cachexia. Approved in Japan as Adlumiz (2021) for cancer cachexia in NSCLC, gastric, pancreatic, and colorectal cancers. Not approved in the US or EU — FDA non-approval driven by failure on co-primary functional endpoint.

§ B · Mechanism of action

Anamorelin is a non-peptide selective agonist at the growth-hormone secretagogue receptor 1a (GHS-R1a). Receptor occupancy in the hypothalamic arcuate nucleus stimulates appetite via NPY/AgRP neurons; pituitary GHS-R1a agonism produces a modest GH/IGF-1 elevation. The clinical profile in cancer cachexia is increased lean body mass and appetite without consistent improvement in handgrip strength or other functional measures.

§ C · Human clinical evidence

Tier 2. Three Phase 3 RCTs in NSCLC cachexia (ROMANA-1 and -2 efficacy, ROMANA-3 safety extension) showed lean body mass and appetite improvement but failed to meet co-primary handgrip strength endpoint. Approved in Japan 2021 across multiple cancer types; FDA Refuse to File 2017 cited the co-primary failure.

§ D · Primary literature

PubMed26906526Temel 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 · The Lancet Oncology · human-phase-3-rctAnamorelin increased lean body mass over 12 weeks vs placebo in both trials; co-primary handgrip strength did not improve.Limitations: Co-primary endpoint failure; modest absolute lean-mass change clinical significance debated.2016

PubMed28472437Currow D et al. — ROMANA 3: a phase 3 safety extension study of anamorelin in advanced non-small-cell lung cancer patients with cachexia · Annals of Oncology · human-phase-3-rct12-week safety extension confirmed no new safety signals with continued anamorelin dosing.Limitations: Open-label extension; selection bias for tolerators.2017

§ F · Safety signal

Class concern: GHS-R1a agonism elevates IGF-1 and may worsen insulin resistance / glucose tolerance — relevant for diabetic populations. ROMANA-3 reported no meaningful safety signal over 24 weeks in the cachexia population.

§ H · Regulatory status

Regulatory status

FDA status:: Not FDA-approved

§ I · Notable gaps and controversies

Co-primary endpoint design (lean mass AND grip strength) was a regulatory inflection point — the broader cachexia community has since debated whether grip strength is the right functional anchor for this indication. Anamorelin is not interchangeable with research-grade powder sold by peptide vendors.