Chemistry:Anamorelin
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| Routes of administration | Oral |
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| Elimination half-life | 6–7 hours[1] |
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| Formula | C31H42N6O3 |
| Molar mass | 546.716 g·mol−1 |
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Anamorelin (INN) (developmental code names ONO-7643, RC-1291, ST-1291), also known as anamorelin hydrochloride (USAN, JAN), is a non-peptide, orally-active, centrally-penetrant, selective agonist of the ghrelin/growth hormone secretagogue receptor (GHSR) with appetite-enhancing and anabolic effects which is under development by Helsinn Healthcare SA for the treatment of cancer cachexia and anorexia.[2][3][4]
Anamorelin significantly increases plasma levels of growth hormone (GH), insulin-like growth factor 1 (IGF-1), and insulin-like growth factor-binding protein 3 (IGFBP-3) in humans, without affecting plasma levels of prolactin, cortisol, insulin, glucose, adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), or thyroid-stimulating hormone (TSH).[3][5] In addition, anamorelin significantly increases appetite, overall body weight, lean body mass, and muscle strength,[4][5] with increases in body weight correlating directly with increases in plasma IGF-1 levels.[3]
As of February 2016, anamorelin has completed phase III clinical trials for the treatment of cancer cachexia and anorexia associated with non-small-cell lung carcinoma.[6][7]
On 18 May 2017, the European Medicines Agency recommended the refusal of the marketing authorisation for the medicinal product, intended for the treatment of anorexia, cachexia or unintended weight loss in patients with non-small cell lung cancer. Helsinn requested a re-examination of the initial opinion. After considering the grounds for this request, the European Medicines Agency re-examined the opinion, and confirmed the refusal of the marketing authorisation on 14 September 2017.[8] The European Medicines Agency concluded that the studies show a marginal effect of anamorelin on lean body mass and no proven effect on hand grip strength or patients’ quality of life. In addition, following an inspection at clinical study sites, the agency considered that the safety data on the medicine had not been recorded adequately. Therefore, the agency was of the opinion that the benefits of anamorelin did not outweigh its risks.[9]
See also
- List of growth hormone secretagogues
References
- ↑ "An open-label clinical trial of the effects of age and gender on the pharmacodynamics, pharmacokinetics and safety of the ghrelin receptor agonist anamorelin". Clinical Pharmacology in Drug Development 4 (2): 112–120. March 2015. doi:10.1002/cpdd.175. PMID 26640742.
- ↑ "Anamorelin hydrochloride in the treatment of cancer anorexia-cachexia syndrome". Future Oncology 10 (5): 789–802. April 2014. doi:10.2217/fon.14.14. PMID 24472001.
- ↑ 3.0 3.1 3.2 "Pharmacodynamic hormonal effects of anamorelin, a novel oral ghrelin mimetic and growth hormone secretagogue in healthy volunteers". Growth Hormone & IGF Research 19 (3): 267–73. June 2009. doi:10.1016/j.ghir.2008.12.003. PMID 19196529.
- ↑ 4.0 4.1 "Anamorelin for patients with cancer cachexia: an integrated analysis of two phase 2, randomised, placebo-controlled, double-blind trials". The Lancet. Oncology 16 (1): 108–16. January 2015. doi:10.1016/S1470-2045(14)71154-4. PMID 25524795.
- ↑ 5.0 5.1 "Therapeutic potential of anamorelin, a novel, oral ghrelin mimetic, in patients with cancer-related cachexia: a multicenter, randomized, double-blind, crossover, pilot study". Supportive Care in Cancer 21 (1): 129–37. January 2013. doi:10.1007/s00520-012-1500-1. PMID 22699302.
- ↑ "Anamorelin hydrochloride for the treatment of cancer-anorexia-cachexia in NSCLC". Expert Opinion on Pharmacotherapy 16 (8): 1245–53. June 2015. doi:10.1517/14656566.2015.1041500. PMID 25945893.
- ↑ "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 17 (4): 519–531. April 2016. doi:10.1016/S1470-2045(15)00558-6. PMID 26906526.
- ↑ "Adlumiz". European Medicines Agency. 17 September 2018. https://www.ema.europa.eu/en/medicines/human/EPAR/adlumiz.
- ↑ "Refusal of the marketing authorisation for Adlumiz (anamorelin hydrochloride): Outcome of re-examination". European Medicines Agency. 15 September 2017. http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion_-_Initial_authorisation/human/003847/WC500228047.pdf.
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