Approved & therapeutic
Anamorelin
Edurmiz (Japan); Adlumiz; ONO-7643
Anamorelin is an orally active, non-peptide ghrelin receptor agonist developed for cancer cachexia. It is approved in Japan for cachexia associated with several cancers, was refused marketing authorisation in the European Union, and is not FDA approved in the United States.
- Status
- Anamorelin is approved in at least one country outside the U.S. but not approved by the FDA.
- Evidence
- Human trials. Published clinical trials in people report results.
- Half-life
- Terminal half-life of approximately 8 to 10 hours per the pharmacokinetics section of the Japanese prescribing information (single dose 8.2 to 9.2 hours; repeat dosing 9.2 to 9.6 hours). An earlier human pharmacokinetic study in healthy volunteers at a lower single dose reported 6 to 7 hours. No US label exists.
- How it's taken
- Oral tablet
- Mechanism
- Growth-hormone secretagogue
- Pathways
- GH-releasing peptide, GH axis
How Anamorelin works
Anamorelin binds and activates the growth hormone secretagogue receptor, the receptor for ghrelin, in the hypothalamus and pituitary. This stimulates appetite signalling and increases growth hormone and insulin-like growth factor 1, which together promote gain in body weight and lean mass.
What research has looked at
- In the phase 3 ROMANA 1 and ROMANA 2 trials in cachexia associated with advanced non-small cell lung cancer, anamorelin met the lean body mass co-primary endpoint, significantly increasing lean body mass over 12 weeks compared with placebo (median +0.99 kg versus -0.47 kg in ROMANA 1 and +0.65 kg versus -0.98 kg in ROMANA 2).
- Handgrip strength, the other co-primary endpoint in ROMANA 1 and ROMANA 2, was NOT met; the trials did not demonstrate a functional strength benefit.
- Total body weight and anorexia/cachexia symptom scores were secondary endpoints and improved versus placebo. Overall survival did not differ between arms, and the European Medicines Agency concluded that a quality-of-life benefit was not demonstrated.
- Approved in Japan in January 2021 and launched in April 2021, for cancer cachexia in non-small cell lung, gastric, pancreatic and colorectal cancer. Approval was conditional on a risk management plan and mandatory post-marketing use-results surveillance.
- An interim analysis of Japanese post-marketing surveillance reported weight and appetite outcomes broadly consistent with the trial data, but this is single-arm observational surveillance without a control group, not comparative evidence.
Evidence level: Human trials. Published clinical trials in people report results. These are areas studied or reported, not promised effects.
Reported side effects and risks
- CONTRAINDICATED in patients with congestive heart failure, and in patients with myocardial infarction or angina pectoris, because the drug can suppress cardiac function.
- CONTRAINDICATED in patients with severe cardiac conduction disorders, such as complete atrioventricular block.
- CONTRAINDICATED in patients with moderate to severe hepatic impairment (Child-Pugh class B or C).
- CONTRAINDICATED with strong CYP3A4 inhibitors, including clarithromycin, itraconazole, voriconazole, ritonavir-containing products, cobicistat-containing products, ensitrelvir and ceritinib.
- CONTRAINDICATED in patients with gastrointestinal obstruction or organic lesions that prevent oral food intake, and in patients with known hypersensitivity to anamorelin hydrochloride.
- Warning on the Japanese label: administer only under a physician with sufficient knowledge and experience in the diagnosis and treatment of cancer cachexia, to patients judged appropriate, and only after fully explaining the benefits and risks to the patient or family and obtaining consent.
- Suppression of cardiac conduction is a labeled serious adverse reaction reported in 10.7 percent: ECG abnormalities including marked PR interval or QRS prolongation and QT prolongation, atrioventricular block, tachycardia, bradycardia, palpitations and reduced blood pressure. The label requires periodic ECG, pulse, blood pressure, cardiothoracic ratio and electrolyte monitoring, with discontinuation if abnormalities appear. A fatal arrhythmia with sinus arrest and refractory ventricular tachycardia has been described in a single published case report.
- Hyperglycemia (4.3 percent) and worsening of diabetes (4.3 percent) are labeled serious adverse reactions and can progress to diabetic ketoacidosis. Risk is higher in patients with pre-existing diabetes, in whom hyperglycemia has been a common reason for discontinuation. The label requires periodic blood and urine glucose monitoring.
- Hepatic impairment is a labeled serious adverse reaction reported in 6.4 percent, and the label requires periodic liver function testing.
- Increased risk of serious cardiac toxicity in patients with prior anthracycline exposure.
- Nausea and other gastrointestinal effects.
- Not FDA-approved. There is no US label, no ANDA and no US product; raises growth hormone and IGF-1, so the theoretical concerns that apply to growth hormone axis stimulation, including effects on glucose control, apply here. Long-term safety in cancer populations is not fully characterised and the label notes there is no experience with dosing beyond 12 weeks.
- The European Medicines Agency refused marketing authorisation, concluding the effect on lean body mass was marginal, with no proven effect on handgrip strength or quality of life, alongside insufficient safety documentation. The refusal was confirmed on re-examination in September 2017.
Sources
- PubMed research on Anamorelin · NIH · National Library of Medicine
- DrugBank record for Anamorelin · DrugBank
- Active clinical trials for Anamorelin · U.S. National Library of Medicine
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Anamorelin FAQ
What is Anamorelin?
Anamorelin is an orally active, non-peptide ghrelin receptor agonist developed for cancer cachexia. It is approved in Japan for cachexia associated with several cancers, was refused marketing authorisation in the European Union, and is not FDA approved in the United States.
How does Anamorelin work?
Anamorelin binds and activates the growth hormone secretagogue receptor, the receptor for ghrelin, in the hypothalamus and pituitary. This stimulates appetite signalling and increases growth hormone and insulin-like growth factor 1, which together promote gain in body weight and lean mass.
Is Anamorelin FDA approved?
No. Anamorelin is approved in at least one country outside the U.S. but not approved by the FDA. Evidence level: human trials. Published clinical trials in people report results.
What is the half-life of Anamorelin?
Reported half-life: Terminal half-life of approximately 8 to 10 hours per the pharmacokinetics section of the Japanese prescribing information (single dose 8.2 to 9.2 hours; repeat dosing 9.2 to 9.6 hours). An earlier human pharmacokinetic study in healthy volunteers at a lower single dose reported 6 to 7 hours. No US label exists.
How is Anamorelin taken?
Oral tablet.
What side effects have been reported with Anamorelin?
Reported in the sources: CONTRAINDICATED in patients with congestive heart failure, and in patients with myocardial infarction or angina pectoris, because the drug can suppress cardiac function; CONTRAINDICATED in patients with severe cardiac conduction disorders, such as complete atrioventricular block; CONTRAINDICATED in patients with moderate to severe hepatic impairment (Child-Pugh class B or C); CONTRAINDICATED with strong CYP3A4 inhibitors, including clarithromycin, itraconazole, voriconazole, ritonavir-containing products, cobicistat-containing products, ensitrelvir and ceritinib; CONTRAINDICATED in patients with gastrointestinal obstruction or organic lesions that prevent oral food intake, and in patients with known hypersensitivity to anamorelin hydrochloride; Warning on the Japanese label: administer only under a physician with sufficient knowledge and experience in the diagnosis and treatment of cancer cachexia, to patients judged appropriate, and only after fully explaining the benefits and risks to the patient or family and obtaining consent; Suppression of cardiac conduction is a labeled serious adverse reaction reported in 10.7 percent: ECG abnormalities including marked PR interval or QRS prolongation and QT prolongation, atrioventricular block, tachycardia, bradycardia, palpitations and reduced blood pressure. The label requires periodic ECG, pulse, blood pressure, cardiothoracic ratio and electrolyte monitoring, with discontinuation if abnormalities appear. A fatal arrhythmia with sinus arrest and refractory ventricular tachycardia has been described in a single published case report; Hyperglycemia (4.3 percent) and worsening of diabetes (4.3 percent) are labeled serious adverse reactions and can progress to diabetic ketoacidosis. Risk is higher in patients with pre-existing diabetes, in whom hyperglycemia has been a common reason for discontinuation. The label requires periodic blood and urine glucose monitoring; Hepatic impairment is a labeled serious adverse reaction reported in 6.4 percent, and the label requires periodic liver function testing; Increased risk of serious cardiac toxicity in patients with prior anthracycline exposure; Nausea and other gastrointestinal effects; Not FDA-approved. There is no US label, no ANDA and no US product; raises growth hormone and IGF-1, so the theoretical concerns that apply to growth hormone axis stimulation, including effects on glucose control, apply here. Long-term safety in cancer populations is not fully characterised and the label notes there is no experience with dosing beyond 12 weeks; The European Medicines Agency refused marketing authorisation, concluding the effect on lean body mass was marginal, with no proven effect on handgrip strength or quality of life, alongside insufficient safety documentation. The refusal was confirmed on re-examination in September 2017.
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