Anamorelin

Summary

Anamorelin is an oral ghrelin‑receptor agonist approved in Japan for the treatment of cancer cachexia associated with non‑small‑cell lung, gastric, pancreatic and colorectal cancers. It is intended to counteract the weight loss, loss of lean body mass and reduced appetite that characterize cancer‑related anorexia‑cachexia syndrome.

Mechanism of Action

Anamorelin mimics the gut hormone ghrelin by binding to the growth‑hormone secretagogue receptor (GHS‑R) in the hypothalamus and pituitary. Activation of this receptor stimulates growth‑hormone release, enhances appetite, increases food intake and promotes anabolic pathways that favor lean‑mass accrual. The downstream hormonal changes are thought to underlie its effects on body weight and muscle mass in cachectic patients.

What the Research Shows

Six randomized controlled trials involving 1,641 patients with advanced non‑small‑cell lung cancer were pooled in a meta‑analysis, showing significant gains in total body weight (mean difference 1.78 kg) and lean body mass (mean difference 1.10 kg) versus placebo, together with modest improvement in quality of life. Two phase‑3 ROMANA trials (n≈1,000) confirmed lean‑mass increases (≈0.6–1.0 kg) but found no benefit for hand‑grip strength or overall survival. Review articles note consistent appetite stimulation and weight gain across trials, while also reporting a lack of functional improvement and limited data outside lung cancer. Case reports from Japanese post‑marketing surveillance have highlighted rare cardiac arrhythmias.

Reported Benefits

Evidence from randomized trials indicates that anamorelin reliably increases lean body mass and modestly raises total body weight in patients with cancer cachexia, particularly in advanced non‑small‑cell lung cancer. Improvements in appetite and patient‑reported quality of life have also been documented, and the incidence of serious adverse events appears comparable to placebo.

Limitations of the Evidence

Functional outcomes such as hand‑grip strength and exercise capacity have not improved in trials, and no overall‑survival benefit has been demonstrated. Efficacy appears reduced in severe‑weight‑loss pancreatic cancer, and regulatory approval is currently limited to Japan. The long‑term impact on mortality and muscle function remains uncertain, and cardiac safety signals are based on isolated case reports.

Safety Considerations

Across phase‑3 studies, grade 3‑4 adverse events occurred at similar rates to placebo, with hyperglycaemia reported in fewer than 1 % of treated patients. Post‑marketing case reports have described cardiac arrhythmias, including fatal events, prompting recommendations for cardiac monitoring, especially after the first dose. Overall, the safety profile is considered acceptable but warrants vigilance for rare cardiac effects.

How It Is Administered

Anamorelin is administered orally as a tablet, most commonly at a dose of 100 mg once daily in clinical trials. The formulation is a solid oral dosage intended for daily use in patients with cancer‑related cachexia.

Routes of Administration

Goals & Uses

• Weight gain / lean body massNutritional SupportHigh
• Cancer cachexia treatmentMetabolic/OncologyHigh
• Increase appetiteSymptom ControlHigh
• Quality of life improvement in cancer patientsSupportive OncologyModerate
• Improve quality of lifePatient‑reported OutcomeModerate
• Growth hormone secretionEndocrineHigh
• Lean body mass preservationBody CompositionHigh
• Appetite stimulationNutritionalHigh

Contraindications

• Concurrent strong CYP3A4 inhibitorsDrug InteractionModerate
• Active malignancy with hormone-sensitive tumorsOncologyModerate
• Hypersensitivity to anamorelinAllergyHigh
• Severe hepatic impairmentOrganModerateLiver function concerns
• Diabetes mellitus (uncontrolled)MetabolicModerate
• Hypersensitivity to anamorelin or any excipientsAllergyHigh

Adverse Effects

• EdemaFluid BalanceUncommonSwelling from fluid retention
• Peripheral edemaFluid BalanceUncommonSwelling of the arms or legs
• HyperglycemiaMetabolicUncommonAbnormally high blood glucose
• QTc prolongationCardiacUncommon
• NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
• FatigueGeneralCommonLow energy or tiredness
• Elevated IGF-1EndocrineCommon
• DiarrheaGastrointestinalCommonLoose or frequent stools
• DizzinessNeurologicCommonFeeling faint, lightheaded, or unsteady
• Increased appetiteMetabolicCommon

Drug Interactions

• CYP3A4 inducers (e.g., rifampin)Moderate
• CYP3A4 inhibitors (e.g., ketoconazole)Moderate
• Insulin / antidiabetic agentsModerate
• Strong CYP3A4 inducers (e.g., rifampicin, carbamazepine)Moderate
• QT-prolonging agents (e.g., antiarrhythmics, some antibiotics)Moderate
• Insulin or antidiabetic agentsLow
• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole)High

Population Constraints

• PregnancyReproductive SafetyAbsolute
• Severe renal impairmentOrgan ImpairmentRelative
• Pediatric patientsAgeAbsolute
• Elderly patients (>75 years)AgeRelative
• Patients with uncontrolled diabetesMetabolicRelative
• Pregnant or breastfeeding womenReproductiveRelative
• Severe hepatic impairmentOrgan ImpairmentRelative

Regulatory Status

• European UnionUnapprovedNo marketing authorization in the European Union.
• JPApprovedApproved: cancer cachexiaApproved in Japan (2021) as oral formulation for cancer‑related cachexia.
• United StatesInvestigationalCompleted Phase III trials; not approved by FDA.
• United KingdomUnapprovedNot approved by MHRA; follows EMA negative opinion pre-Brexit.

Approved in Japan for cancer cachexia; not approved in the US or EU, currently under investigation in other regions.

Evidence & Sources

• Anamorelin for advanced non-small-cell lung cancer with cachexia: Systematic review and meta-analysis
  Journal ArticleHighNishie K, et al.2017-01-01T00:00:00.000000Z
• Anamorelin in the Management of Cancer Cachexia: Clinical Efficacy, Challenges, and Future Directions
  Journal ArticleModerateFujii H, et al.2025-01-01T00:00:00.000000Z
• What is next after anamorelin?
  Journal ArticleModerateGarcia JM2017-01-01T00:00:00.000000Z
• Anamorelin in Japanese patients with cancer cachexia: an update
  Journal ArticleModerateWakabayashi H, Arai H, Inui A2023-01-01T00:00:00.000000Z
• Oncology Update: Anamorelin
  Journal ArticleModeratePrommer E2017-01-01T00:00:00.000000Z
• 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
  Journal ArticleModerateTemel JS, et al.2016-01-01T00:00:00.000000Z

Frequently Asked Questions