Evidence memo / GH / IGF axis

Anamorelin

Also: Adlumiz · ONO-7643 · RC-1291 · ghrelin receptor agonist

Anamorelin (Adlumiz) is an oral, ghrelin-like drug for cancer cachexia, the appetite loss and muscle wasting that comes with advanced cancer. In large trials it added weight and lean body mass and improved appetite, but it did not improve measured muscle strength, which is why Japan and Taiwan approved it while the FDA declined. The Watchlist read is that it is a real but partial win for a hard problem, and a clean lesson that adding lean mass on a scan is not the same as proven functional benefit.

Controlled human dataPhase 2 / Phase 3Investigational

The verdict

Our read at a glance.

Whether anamorelin's ability to add weight and lean body mass in cancer cachexia, shown in Phase 3 trials, translates into real functional benefit such as strength, physical function, or survival, the gap that kept it from FDA approval.

The signal
In two large Phase 3 trials in lung-cancer cachexia (ROMANA 1 and ROMANA 2), anamorelin increased body weight and lean body mass and improved appetite versus placebo over 12 weeks. But it did not improve handgrip strength, a co-primary measure of muscle function, and did not show a survival benefit. It is approved in Japan and Taiwan for cancer cachexia; the FDA declined approval, with its advisory committee citing the missing functional benefit.
The unknown
Whether the weight and lean mass it adds ever translates into people feeling stronger, functioning better, or living longer. Lean mass went up while measured strength did not, which is the core unresolved question and the reason regulators split on it.
Our read
The most rigorously tested ghrelin-receptor drug for muscle wasting, and a clean lesson in why bigger is not always better. Anamorelin reliably adds weight and lean body mass in cancer cachexia, but it did not improve measured strength, which is why Japan and Taiwan approved it while the FDA did not. Read it as a real but partial win for a hard problem, and as evidence that switching on the ghrelin receptor (the same target as MK-677) can grow tissue without a proven functional payoff.

The mechanism

How it works.

Ghrelin is the body's hunger hormone; it tells the brain to eat and nudges the pituitary to release growth hormone. Anamorelin is an orally active molecule built to act like ghrelin at its receptor, so it boosts appetite and raises growth hormone and IGF-1, which together push the body toward gaining weight and building lean tissue. In cancer cachexia, where appetite collapses and muscle melts away, that is exactly the direction you want. The catch its trials exposed is that adding lean mass on a body scan did not translate into a stronger grip, so the tissue it builds may not be the functional muscle that helps people do more. Because it works through the same receptor as the popular secretagogue MK-677, it is effectively the carefully studied version of that idea.

Safety & regulatory boundary

The consequential part.

Anamorelin is generally well tolerated; because it raises growth hormone and IGF-1, it can raise blood sugar and is used cautiously in people with diabetes. It is approved only in Japan and Taiwan, only for cancer cachexia in specific cancers, and is not FDA-approved or a general muscle-building or anti-aging drug. Adlumiz is not the same as research-labeled anamorelin sold online, and the trial evidence is specifically about cancer-related wasting, not healthy-person muscle gain.

What's next

What we're watching.

Trials testing whether anamorelin, alone or alongside exercise and nutrition, improves physical function and survival rather than only weight and lean mass, plus longer-term safety of raising growth hormone and IGF-1 in people with cancer.

Context

Why this is discussed.

Cancer cachexia, the wasting that comes with advanced cancer, has almost no good treatments, and anamorelin is the most rigorously tested ghrelin-receptor drug for it. It is also the carefully studied cousin of the ghrelin-receptor compounds (like MK-677) sold for muscle and anti-aging, so its trial results are the closest thing to a real test of whether switching on that receptor builds useful muscle.

The evidence base

20 cited references.

Keep reading

Related published memos.