{"entity":{"id":"ponsegromab-phase-2","kind":"trial","name":"Ponsegromab phase 2 in cancer cachexia","aka":[],"tldr":"The first drug to hit the hormone behind cancer wasting: patients on the highest dose gained nearly 3 kg more than placebo in 12 weeks and reported better appetite and more activity.","summary":"187 patients with cachexia (weight loss at least 5%, or 2% with BMI under 20) and GDF-15 at least 1,500 pg/mL were randomised. The primary endpoint, change in body weight at 12 weeks, showed placebo-adjusted gains of 1.22 kg (100 mg), 1.92 kg (200 mg) and 2.81 kg (400 mg). At 400 mg there were also improvements in appetite and cachexia symptoms, physical activity measured by accelerometer, and lumbar skeletal muscle index, and no increase in adverse events versus placebo. Follow-on work: a phase 2/3 programme in pancreatic cancer cachexia (NCT06989437, recruiting) and planned lung cancer studies, with functional and survival endpoints. The trial is the proof of concept that cachexia is a drug-treatable disease; it did not test survival, and 12 weeks is short.","status":"positive","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov NCT05546476","url":"https://clinicaltrials.gov/study/NCT05546476"},{"label":"Groarke et al. (NEJM 2024)","url":"https://doi.org/10.1056/NEJMoa2409515"}],"tags":[],"related":["idea-cachexia-gdf15-prevention","idea-bio2-gdf15-plus-exercise","idea-bio2-gdf15-stratified-enrolment"],"cancers":["nsclc","pancreatic","colorectal"],"sections":["nutrition-lifestyle","supportive-care"],"technologies":["cachexia-therapy","cachexia-appetite-pharmacotherapy"],"targets":[],"drugs":[],"companies":["pfizer"],"institutions":[],"pathways":["cachexia-biology"],"terms":["cachexia","body-composition"],"trials":["nct06989437"],"people":[],"bottlenecks":["b-cachexia-supportive"],"keyPapers":["paper-groarke-ponsegromab-cancer-cachexia-nejm-2024"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05546476","phase":"2","setting":"NSCLC, pancreatic or colorectal cancer with cachexia and elevated serum GDF-15: ponsegromab 100, 200 or 400 mg subcutaneously every 4 weeks vs placebo for 12 weeks","sponsor":"Pfizer","result":"Placebo-adjusted weight gain 2.81 kg at 400 mg over 12 weeks; improved appetite and activity.","started":"2022-11-21","startedType":"actual","yearReported":2024,"enrolled":187,"enrolledBasis":"registry","outcomes":[{"endpoint":"Change in body weight at 12 weeks (placebo-adjusted)","primary":true,"unit":"kg","arms":[{"name":"Ponsegromab 400 mg","value":2.81},{"name":"Ponsegromab 200 mg","value":1.92},{"name":"Ponsegromab 100 mg","value":1.22},{"name":"Placebo","value":0}],"source":"https://doi.org/10.1056/NEJMoa2409515"}],"replication":"Phase 2/3 in pancreatic cancer cachexia underway (NCT06989437)."},"route":"/trials/ponsegromab-phase-2/","neighbours":{"idea":[{"id":"idea-bio2-gdf15-plus-exercise","kind":"idea","name":"Combine the new anti-wasting antibody with exercise and protein","route":"/ideas/idea-bio2-gdf15-plus-exercise/"},{"id":"idea-bio2-gdf15-stratified-enrolment","kind":"idea","name":"Select cachexia trial patients by the hormone driving their wasting","route":"/ideas/idea-bio2-gdf15-stratified-enrolment/"},{"id":"idea-cachexia-gdf15-prevention","kind":"idea","name":"Treat cachexia before it starts","route":"/ideas/idea-cachexia-gdf15-prevention/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"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":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}],"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/"}],"trial":[{"id":"nct06989437","kind":"trial","name":"A Study to Learn About the Medicine Ponsegromab in Adults With Cancer of the Pancreas Which Has Spread and Caused Significant Body Weight Loss and Fatigue","route":"/trials/nct06989437/"}],"bottleneck":[{"id":"b-cachexia-supportive","kind":"bottleneck","name":"Cachexia, toxicity and the limits of the patient","route":"/bottlenecks/b-cachexia-supportive/"}],"paper":[{"id":"paper-groarke-ponsegromab-cancer-cachexia-nejm-2024","kind":"paper","name":"Ponsegromab for the Treatment of Cancer Cachexia","route":"/key-papers/paper-groarke-ponsegromab-cancer-cachexia-nejm-2024/"}],"roadmap":[{"id":"nutrition-lifestyle-roadmap","kind":"roadmap","name":"Diet, exercise and lifestyle roadmap: causes established → interventions that disappointed → exercise proven as treatment","route":"/roadmaps/nutrition-lifestyle-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/"}]}}