Cachexia-directed therapy (GDF-15 blockade)
Treating the wasting that kills many cancer patients, by blocking the hormone that suppresses appetite.
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.
How it works
Neutralising circulating GDF-15 removes the anorexigenic signal at the GFRAL receptor in the hindbrain, restoring appetite and lean mass.
- Addresses a cause of death and of treatment discontinuation, not the tumour
- Clear biomarker for patient selection
- Phase 2 met its weight endpoints
- Weight gain must translate into function and survival
- Cachexia is multifactorial; GDF-15 is one pathway
- Phase 3 data pending
Latest papers
topQuery for this technology: (TITLE:"Cachexia-directed therapy" OR ABSTRACT:"Cachexia-directed therapy" OR TITLE:"GDF-15 blockade" OR ABSTRACT:"GDF-15 blockade") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Cachexia-directed therapy (GDF-15 blockade), not a curated reading list.