{"entity":{"id":"romana-1-2","kind":"trial","name":"ROMANA 1 and ROMANA 2","aka":[],"tldr":"ROMANA 1 and 2 were two phase 3 trials of an appetite-hormone mimic in lung cancer patients with wasting. Patients gained muscle but not grip strength, which split regulators: approved in Japan, rejected in Europe.","summary":"ROMANA 1 (n=484) and ROMANA 2 (n=495) were identical double-blind trials with co-primary endpoints of lean body mass (DXA) and handgrip strength over 12 weeks. Lean body mass increased with anamorelin (ROMANA 1: +0.99 kg vs -0.47 kg; ROMANA 2: +0.65 kg vs -0.98 kg), and body weight, appetite and anorexia-cachexia symptom scores improved, but handgrip strength did not differ from placebo in either trial. Hyperglycaemia and nausea were the main adverse events. The EMA refused marketing authorisation in 2017 citing the absence of a functional benefit; Japan approved anamorelin (Adlumiz) in 2021 for NSCLC, gastric, pancreatic and colorectal cancer cachexia. ROMANA established that lean mass can be pharmacologically increased in cachexia, and that regulators want function or survival, which shaped the endpoint strategy for GDF-15 antagonists.","status":"mixed","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov NCT01387269","url":"https://clinicaltrials.gov/study/NCT01387269"},{"label":"ClinicalTrials.gov NCT01387282","url":"https://clinicaltrials.gov/study/NCT01387282"},{"label":"Temel et al. (Lancet Oncol 2016)","url":"https://doi.org/10.1016/S1470-2045(15)00558-6"}],"tags":[],"related":["idea-bio2-anamorelin-access","idea-bio2-cachexia-function-endpoint"],"cancers":["nsclc"],"sections":["nutrition-lifestyle","supportive-care"],"technologies":["cachexia-appetite-pharmacotherapy","cachexia-therapy"],"targets":[],"drugs":[],"companies":["helsinn"],"institutions":["ncc-japan"],"pathways":["cachexia-biology"],"terms":["cachexia","sarcopenia","body-composition"],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-regulatory-fragmentation"],"keyPapers":["paper-romana-1-2-lancet-oncol-2016"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT01387269","phase":"3","setting":"Unresectable stage III/IV NSCLC with cachexia (weight loss over 5% in 6 months or BMI under 20): anamorelin 100 mg/day vs placebo for 12 weeks","sponsor":"Helsinn Therapeutics","result":"Lean body mass increased (about +1 to +1.5 kg vs placebo); handgrip strength unchanged.","started":"2011-07","yearReported":2016,"enrolled":979,"enrolledBasis":"registry","outcomes":[{"endpoint":"Change in lean body mass over 12 weeks (ROMANA 1)","primary":true,"unit":"kg","arms":[{"name":"Anamorelin","n":323,"value":0.99},{"name":"Placebo","n":161,"value":-0.47}],"p":"<0.0001","source":"https://doi.org/10.1016/S1470-2045(15)00558-6"},{"endpoint":"Change in lean body mass over 12 weeks (ROMANA 2)","primary":true,"unit":"kg","arms":[{"name":"Anamorelin","n":330,"value":0.65},{"name":"Placebo","n":165,"value":-0.98}],"p":"<0.0001","source":"https://doi.org/10.1016/S1470-2045(15)00558-6"}],"replication":"Japanese phase 2/3 trials (ONO-7643) in NSCLC and GI cancers reproduced the lean mass effect; the ROMANA 3 extension confirmed safety over 24 weeks."},"route":"/trials/romana-1-2/","neighbours":{"idea":[{"id":"idea-bio2-anamorelin-access","kind":"idea","name":"Get the one approved appetite drug licensed beyond a single country","route":"/ideas/idea-bio2-anamorelin-access/"},{"id":"idea-bio2-cachexia-function-endpoint","kind":"idea","name":"Qualify a physical function endpoint so anti-wasting drugs can be approved","route":"/ideas/idea-bio2-cachexia-function-endpoint/"}],"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"section":[{"id":"nutrition-lifestyle","kind":"section","name":"Diet, Exercise & Lifestyle","route":"/fronts/nutrition-lifestyle/"},{"id":"supportive-care","kind":"section","name":"Supportive Care & Survivorship","route":"/fronts/supportive-care/"}],"technology":[{"id":"cachexia-appetite-pharmacotherapy","kind":"technology","name":"Cachexia pharmacotherapy: GDF-15 blockade, anamorelin, olanzapine","route":"/technologies/cachexia-appetite-pharmacotherapy/"},{"id":"cachexia-therapy","kind":"technology","name":"Cachexia-directed therapy (GDF-15 blockade)","route":"/technologies/cachexia-therapy/"}],"company":[{"id":"helsinn","kind":"company","name":"Helsinn","route":"/companies/helsinn/"}],"institution":[{"id":"ncc-japan","kind":"institution","name":"National Cancer Center Hospital","route":"/institutions/ncc-japan/"}],"pathway":[{"id":"cachexia-biology","kind":"pathway","name":"Cancer cachexia","route":"/pathways/cachexia-biology/"}],"term":[{"id":"body-composition","kind":"term","name":"Body composition (lean mass, fat mass, visceral fat)","route":"/terms/body-composition/"},{"id":"cachexia","kind":"term","name":"Cancer cachexia","route":"/terms/cachexia/"},{"id":"sarcopenia","kind":"term","name":"Sarcopenia","route":"/terms/sarcopenia/"}],"bottleneck":[{"id":"b-cachexia-supportive","kind":"bottleneck","name":"Cachexia, toxicity and the limits of the patient","route":"/bottlenecks/b-cachexia-supportive/"},{"id":"b-regulatory-fragmentation","kind":"bottleneck","name":"Regulatory divergence between regions","route":"/bottlenecks/b-regulatory-fragmentation/"}],"paper":[{"id":"paper-romana-1-2-lancet-oncol-2016","kind":"paper","name":"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","route":"/key-papers/paper-romana-1-2-lancet-oncol-2016/"}],"roadmap":[{"id":"survivorship-roadmap","kind":"roadmap","name":"Supportive care and survivorship roadmap: making treatment bearable → proving it extends life → caring for tens of millions afterwards","route":"/roadmaps/survivorship-roadmap/"}]}}