Anamorelin: An Oral Ghrelin-Based Drug for Cancer-Related Muscle Wasting and Appetite Loss

What the researchers found

Anamorelin hydrochloride demonstrated significant improvements across multiple cachexia endpoints in preclinical and clinical studies:

- Significant appetite enhancement via potent ghrelin receptor activation

- Improvements in body weight and lean body mass compared to placebo

- Improvements in handgrip strength (a key functional measure)

- Stimulation of growth hormone and IGF-1 secretion (anabolic effects)

Critically, the growth hormone and IGF-1 stimulation did not promote tumor growth, and overall survival was not compromised in cancer patients. The drug was well tolerated with no dose-limiting toxicities identified across studies completed at the time of this review. Phase III studies in non-small-cell lung cancer cachexia were ongoing.

Why it matters

Cancer cachexia affects up to 80% of advanced cancer patients and directly contributes to mortality, yet treatment options remain extremely limited. An oral drug that can improve appetite, build lean mass, and increase strength without promoting tumor growth or requiring injections would represent a major advance in supportive cancer care. Anamorelin's ghrelin-mimicking mechanism addresses the biological root of cachexia rather than just treating symptoms.

How the study worked

This is a review article summarizing preclinical and clinical study data for anamorelin hydrochloride in the treatment of cancer anorexia-cachexia syndrome, focusing on its application in non-small-cell lung cancer patients. The review covers pharmacology, efficacy data, safety profile, and the status of ongoing Phase III clinical trials.

What this study cannot tell us

This is a review article published while Phase III trials were still ongoing, so definitive efficacy conclusions could not be drawn. The review focuses specifically on NSCLC cachexia, and generalizability to other cancer types was not established. Long-term safety data were limited. The review does not report specific numerical results from clinical trials in the abstract.

How to read the evidence

This is a review article summarizing preclinical and early clinical data, published while Phase III trials were ongoing. It provides a comprehensive overview but does not present definitive clinical trial results.

When this study was published

Published in 2014, this review predates the completion of the ROMANA Phase III trials. Anamorelin has since been approved in Japan (2021) for cancer cachexia but has not received FDA or EMA approval.

The bigger picture

Ghrelin-based therapies represent a fundamentally different approach to cancer cachexia compared to appetite stimulants like megestrol acetate or corticosteroids. By targeting the ghrelin receptor, anamorelin activates both appetite and anabolic pathways simultaneously. Since this 2014 review, anamorelin has been approved in Japan for cancer cachexia and has completed Phase III trials (ROMANA studies), though it has not received FDA or EMA approval, partly because improvements in lean mass did not consistently translate to functional gains.

Questions still open

• Do the improvements in lean body mass from anamorelin translate to meaningful functional and survival benefits in cancer patients?
• Could anamorelin be effective for cachexia in cancers other than non-small-cell lung cancer?
• What is the optimal timing for initiating ghrelin-based therapy in the cachexia trajectory — early intervention or after significant wasting has occurred?

Common questions

Read the original research

Anamorelin hydrochloride in the treatment of cancer anorexia-cachexia syndrome.

Future oncology (London, England), 10(5), 789-802

Citation

Currow, David C; Abernethy, Amy P. (2014). Anamorelin hydrochloride in the treatment of cancer anorexia-cachexia syndrome.. Future oncology (London, England), 10(5), 789-802. https://doi.org/10.2217/fon.14.14