Guides May 18, 2026

Anamorelin: Approved in Japan, Rejected in Europe, and Never Approved by FDA

Anamorelin is an oral ghrelin receptor agonist and the first drug approved anywhere for cancer cachexia, but only in Japan. Here is why Europe and the U.S. said no.

Anamorelin is one of the cleanest case studies in how the same drug class can get three very different regulatory answers.

It is:

an oral ghrelin receptor agonist
developed for cancer cachexia
approved in Japan
rejected by the European Medicines Agency
and never approved by the FDA

That makes it unusually useful for understanding both the ghrelin mimetic class and the realities of drug approval.

It also makes anamorelin the best real-world counterpoint to compounds like MK-677.

What anamorelin is

Anamorelin is an orally active, selective ghrelin receptor agonist.¹²

It is best known by:

anamorelin hydrochloride
Adlumiz in Japan
and the development code ONO-7643²

Mechanistically, it activates GHSR-1a, the growth hormone secretagogue receptor and the same receptor targeted by the natural hormone ghrelin.¹³

That receptor link is the main reason anamorelin matters to people who already follow MK-677 / ibutamoren.

Both compounds sit in the same broad lane:

oral ghrelin mimetics
same receptor target
appetite and anabolic signaling as the therapeutic logic

The difference is that anamorelin actually made it through late-stage oncology development and reached real regulatory review.

Why cancer cachexia was such an important target

The indication matters.

Anamorelin was developed for cancer cachexia, the syndrome of involuntary weight loss, appetite decline, muscle wasting, and metabolic disruption that affects many people with advanced cancer.

The 2021 Japanese regulatory review article notes that cachexia affects a large proportion of patients with advanced cancer and had no approved pharmacologic treatment before anamorelin’s approval in Japan.²

So this was not a cosmetic or quality-of-life side story.

It was an attempt to treat one of oncology supportive care’s hardest unsolved problems.

That is part of why the approval milestone in Japan was historically meaningful even though the evidence base remained disputed.

The ROMANA trials are why this became a global regulatory story

The key pivotal program was ROMANA 1 and ROMANA 2, two randomized, double-blind, placebo-controlled phase 3 studies in patients with advanced non-small-cell lung cancer and cachexia.⁴

Together, they enrolled nearly 1,000 patients:

ROMANA 1: n=484
ROMANA 2: n=495⁴

Both studies randomized patients 2:1 to:

anamorelin 100 mg orally once daily
or placebo

for 12 weeks.⁴

The co-primary endpoints were:

change in lean body mass
and change in handgrip strength⁴

This is where the whole regulatory divergence starts.

What anamorelin did achieve

Anamorelin did succeed on one of the big endpoints.

In the pooled phase 3 publication, it significantly improved lean body mass:

in ROMANA 1, the least-squares mean change was +1.10 kg with anamorelin versus -0.44 kg with placebo
in ROMANA 2, the least-squares mean change was +0.75 kg with anamorelin versus -0.96 kg with placebo⁴

Body weight also improved.

And the broader development narrative around anamorelin consistently emphasized:

better appetite
weight gain
and anabolic / IGF-1-linked effects

So the drug was not “inactive.”

The problem was that regulators were not looking for lean mass gain alone.

What it failed to prove

The same Lancet Oncology paper reported that anamorelin did not significantly improve handgrip strength in either ROMANA trial.⁴

That failure became the core problem.

Why?

Because regulators do not just want to know whether a drug changes a body-composition measurement.

They also want to know whether those changes translate into something that matters clinically:

function
quality of life
meaningful daily capability

Anamorelin improved lean body mass.

But it did not convincingly prove that patients were stronger.

That split result is the central lesson of the drug’s regulatory history.

Why Europe said no

The EMA was explicit.

In its refusal document, the agency wrote that the main studies showed only a marginal effect on lean body mass and no proven effect on hand grip strength or patients’ quality of life.¹

The document also states that after an inspection at clinical study sites, CHMP concluded that the safety data had not been recorded adequately, which meant a full evaluation of potential risks was not possible.¹

That is a bigger issue than many summaries admit.

The EMA’s problem was not simply:

“we wanted more weight gain”

It was:

the efficacy case was not strong enough on clinically meaningful outcomes
and the safety documentation itself created confidence problems

The initial negative opinion came on 18 May 2017, and after re-examination the refusal was confirmed on 14 September 2017.¹

That is about as clear a regulatory rejection as you can get.

Why the FDA never approved it

The U.S. story is simpler but still important.

Anamorelin never achieved FDA approval.

The broader development history described in reviews and regulatory summaries shows the company pursued global development, but unlike in Japan, it did not secure a U.S. approval path.²³

The key takeaway is not that the FDA issued some dramatic public refusal document exactly like the EMA did.

It is that the program did not produce an approved U.S. oncology supportive-care drug.

So the class reached approval somewhere, but not in the world’s biggest drug market.

Why Japan said yes

Japan took a different view.

According to the 2021 Journal of Cachexia, Sarcopenia and Muscle review by Wakabayashi, Arai, and Inui, Japan granted anamorelin approval on January 22, 2021 for cancer cachexia in:

non-small-cell lung cancer
gastric cancer
pancreatic cancer
colorectal cancer²

That made anamorelin the first drug ever approved anywhere for cancer cachexia.²

The same review explains that this decision was based not just on the global ROMANA program, but also on Japanese clinical data, including:

ONO-7643-04 in non-small-cell lung cancer
ONO-7643-05 in gastrointestinal cancers²

So the Japan approval was not just “same exact file, different mood.”

It reflected:

different population-specific evidence
different regulatory weighting
and a different willingness to accept what the drug had shown

That is what makes the divergence analytically interesting.

The post-marketing safety story is real too

The Japan approval did not end the uncertainty.

Real-world post-marketing surveillance in Japan has now added a much larger safety dataset.

An interim analysis published in 2024 reported a safety analysis set of 6,016 patients treated with anamorelin after Japanese approval.⁵

That is important because it gives a much better picture of real-world tolerability than the pre-approval trials alone.

But it also reinforces why safety monitoring still matters.

The same report and later literature on conduction disorders highlight the need to watch:

cardiac conduction effects
arrhythmia-related issues
and other clinically relevant adverse events⁵⁶

The 2024 conduction-defects review is especially blunt that fatal arrhythmias should be monitored carefully.⁶

So even in the one country where the drug reached approval, this is not a carefree supportive-care medicine.

Why the MK-677 comparison is so useful

If you watched the MK-677 story closely, anamorelin helps answer a question that video naturally raises:

Can the oral ghrelin mimetic class ever actually succeed regulatorily?

Anamorelin’s answer is:

yes, but only narrowly, and only in one major jurisdiction so far.

That matters because MK-677 often gets discussed as if its failure to become a real drug means the class itself was doomed.

Anamorelin shows that is too simple.

The class can produce:

a real pharmaceutical development program
phase 3 oncology trials
and even approval

But it also shows how difficult that path is.

Same receptor class. Same oral convenience. Very different commercial and regulatory outcomes.

The real lesson of anamorelin

The strongest honest summary is:

anamorelin is a legitimate pharmaceutical ghrelin mimetic
it achieved something historically meaningful in Japan
it failed to convince Europe
it never reached FDA approval
and the reason comes down largely to the difference between changing lean mass and proving clinically meaningful functional benefit

That is what makes it worth understanding.

It is not a gray-market curiosity.

It is a real approved drug in one country that became a live demonstration of how:

the same mechanism
the same broad development story
and overlapping evidence

can still produce three different regulatory answers.