Anamorelin

Summary

Anamorelin is an oral ghrelin receptor agonist developed for the treatment of cancer cachexia and anorexia. It stimulates GH secretion and appetite, promoting lean body mass preservation and weight gain in cachectic cancer patients. Approved in Japan; not approved in the US or EU.

Mechanism of Action

Selective agonist of the ghrelin/growth hormone secretagogue receptor (GHS-R1a), stimulating growth hormone release from the pituitary and activating hypothalamic appetite centers, leading to increased appetite and anabolic effects via IGF-1 upregulation.

Routes of Administration

Goals & Uses

• Cancer cachexia treatmentMetabolic/OncologyHigh
• Quality of life improvement in cancer patientsSupportive OncologyModerate
• 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
• Diabetes mellitus (uncontrolled)MetabolicModerate

Adverse Effects

• Peripheral edemaFluid BalanceUncommonSwelling of the arms or legs
• HyperglycemiaMetabolicCommonAbnormally high blood glucose
• QTc prolongationCardiacUncommon
• NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
• FatigueGeneralCommonLow energy or tiredness
• Elevated IGF-1EndocrineCommon

Drug Interactions

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

Population Constraints

• PregnancyReproductive SafetyAbsolute
• Severe renal impairmentOrgan ImpairmentRelative
• Pediatric patientsAgeRelative
• Elderly patients (>75 years)AgeRelative
• Severe hepatic impairmentOrgan ImpairmentRelative

Regulatory Status

• European UnionUnapprovedEMA issued a negative opinion in 2017 for cancer cachexia/anorexia in NSCLC; concerns about lack of clinically meaningful benefit on muscle function.
• United StatesUnapprovedFDA rejected NDA in February 2017 citing failure to demonstrate improvement in handgrip strength as a co-primary endpoint despite improvements in body weight.
• United KingdomUnapprovedNot approved by MHRA; follows EMA negative opinion pre-Brexit.

Approved in Japan (2021) as Adlumiz for cancer cachexia/anorexia in non-small cell lung cancer. FDA rejected NDA in 2017 citing insufficient evidence on muscle strength (handgrip) endpoints. EMA issued a negative opinion in 2017 for similar reasons.

Evidence & Sources

No sources recorded yet.