{"entity":{"id":"cachexia-therapy","kind":"technology","name":"Cachexia-directed therapy (GDF-15 blockade)","aka":[],"tldr":"Cachexia-directed therapy treats cancer wasting by blocking GDF-15, a hormone that rises in advanced cancer and acts on the brainstem to suppress appetite. Pfizer's antibody ponsegromab improved weight in a phase 2 trial and is in phase 2/3 in pancreatic cancer cachexia; whether weight gain translates into function is the open question.","summary":"GDF-15 rises in advanced cancer and acts on the brainstem to suppress appetite. Pfizer's ponsegromab, a GDF-15 antibody, improved weight in a phase 2 in patients with elevated GDF-15 (NCT05546476, completed) and has moved into a phase 2/3 programme in pancreatic cancer-associated cachexia (NCT06989437, recruiting since October 2025), with a further lung cancer study planned (NCT07663630). Cachexia has no approved disease-modifying therapy, so a positive phase 3 would be a first.","status":"phase-3","asOf":"2026-09-08","links":[{"label":"Ponsegromab phase 2/3 in PDAC cachexia (NCT06989437)","url":"https://clinicaltrials.gov/study/NCT06989437"},{"label":"Phase 2 (NCT05546476)","url":"https://clinicaltrials.gov/study/NCT05546476"}],"tags":["frontier","promising"],"related":[],"cancers":["pancreatic","nsclc"],"sections":["supportive-care","nutrition-lifestyle"],"technologies":["geriatric-assessment","exercise-oncology"],"targets":[],"drugs":[],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-cachexia-sarcopenia-and-muscle"],"dependsOn":[],"notes":[],"principle":"Neutralising circulating GDF-15 removes the anorexigenic signal at the GFRAL receptor in the hindbrain, restoring appetite and lean mass.","strengths":["Addresses a cause of death and of treatment discontinuation, not the tumour","Clear biomarker for patient selection","Phase 2 met its weight endpoints"],"limitations":["Weight gain must translate into function and survival","Cachexia is multifactorial; GDF-15 is one pathway","Phase 3 data pending"]},"route":"/technologies/cachexia-therapy/","neighbours":{"cancer":[{"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":"exercise-oncology","kind":"technology","name":"Exercise & lifestyle oncology","route":"/technologies/exercise-oncology/"},{"id":"omega3-epa-cachexia","kind":"technology","name":"Fish oil (EPA) for cancer weight loss","route":"/technologies/omega3-epa-cachexia/"},{"id":"geriatric-assessment","kind":"technology","name":"Geriatric assessment","route":"/technologies/geriatric-assessment/"},{"id":"hydrazine-sulfate","kind":"technology","name":"Hydrazine sulfate","route":"/technologies/hydrazine-sulfate/"},{"id":"muscle-recovery-after-cancer-treatment","kind":"technology","name":"Muscle and strength after treatment: sarcopenia, cachexia and what rebuilds","route":"/technologies/muscle-recovery-after-cancer-treatment/"},{"id":"resistance-training-cachexia","kind":"technology","name":"Resistance training and protein for cachexia and sarcopenia","route":"/technologies/resistance-training-cachexia/"}],"company":[{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}],"journal":[{"id":"journal-of-cachexia-sarcopenia-and-muscle","kind":"journal","name":"Journal of cachexia, sarcopenia and muscle","route":"/journals/journal-of-cachexia-sarcopenia-and-muscle/"}],"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":"cure-paths","kind":"roadmap","name":"Paths to cures: interception, eradication, control","route":"/roadmaps/cure-paths/"},{"id":"frontier-2035","kind":"roadmap","name":"Radical oncology: what could change the war by 2035","route":"/roadmaps/frontier-2035/"},{"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/"}],"term":[{"id":"cachexia","kind":"term","name":"Cancer cachexia","route":"/terms/cachexia/"}],"trial":[{"id":"ponsegromab-phase-2","kind":"trial","name":"Ponsegromab phase 2 in cancer cachexia","route":"/trials/ponsegromab-phase-2/"},{"id":"romana-1-2","kind":"trial","name":"ROMANA 1 and ROMANA 2","route":"/trials/romana-1-2/"}]}}