# Cachexia-directed therapy (GDF-15 blockade)

Source: https://onco.cc/technologies/cachexia-therapy/  
OnCo record `cachexia-therapy` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Technology
- Status: phase-3
- Last checked: 2026-09-08
- Tags: frontier; promising
- 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

## Sources

- Ponsegromab phase 2/3 in PDAC cachexia (NCT06989437): https://clinicaltrials.gov/study/NCT06989437
- Phase 2 (NCT05546476): https://clinicaltrials.gov/study/NCT05546476

## Connected records

- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- fronts: [Diet, Exercise & Lifestyle](https://onco.cc/fronts/nutrition-lifestyle/), [Supportive Care & Survivorship](https://onco.cc/fronts/supportive-care/)
- technologies: [Cachexia pharmacotherapy: GDF-15 blockade, anamorelin, olanzapine](https://onco.cc/technologies/cachexia-appetite-pharmacotherapy/), [Exercise & lifestyle oncology](https://onco.cc/technologies/exercise-oncology/), [Fish oil (EPA) for cancer weight loss](https://onco.cc/technologies/omega3-epa-cachexia/), [Geriatric assessment](https://onco.cc/technologies/geriatric-assessment/), [Hydrazine sulfate](https://onco.cc/technologies/hydrazine-sulfate/), [Muscle and strength after treatment: sarcopenia, cachexia and what rebuilds](https://onco.cc/technologies/muscle-recovery-after-cancer-treatment/), [Resistance training and protein for cachexia and sarcopenia](https://onco.cc/technologies/resistance-training-cachexia/)
- companies: [Pfizer (incl. Seagen)](https://onco.cc/companies/pfizer/)
- journals: [Journal of cachexia, sarcopenia and muscle](https://onco.cc/journals/journal-of-cachexia-sarcopenia-and-muscle/)
- roadmaps: [Diet, exercise and lifestyle roadmap: causes established → interventions that disappointed → exercise proven as treatment](https://onco.cc/roadmaps/nutrition-lifestyle-roadmap/), [Paths to cures: interception, eradication, control](https://onco.cc/roadmaps/cure-paths/), [Radical oncology: what could change the war by 2035](https://onco.cc/roadmaps/frontier-2035/), [Supportive care and survivorship roadmap: making treatment bearable → proving it extends life → caring for tens of millions afterwards](https://onco.cc/roadmaps/survivorship-roadmap/)
- terms: [Cancer cachexia](https://onco.cc/terms/cachexia/)
- trials: [Ponsegromab phase 2 in cancer cachexia](https://onco.cc/trials/ponsegromab-phase-2/), [ROMANA 1 and ROMANA 2](https://onco.cc/trials/romana-1-2/)

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