# Combine the new anti-wasting antibody with exercise and protein

Source: https://onco.cc/ideas/idea-bio2-gdf15-plus-exercise/  
OnCo record `idea-bio2-gdf15-plus-exercise` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A new antibody blocks the hormone that makes people with cancer lose appetite and weight. Weight regained as muscle, not fat, needs exercise and protein alongside it.

## Summary

GDF-15 is a tumour-derived hormone acting on the brainstem GFRAL receptor to suppress appetite, and a randomised phase 2 of the anti-GDF-15 antibody ponsegromab reported weight gain and improved appetite in cancer cachexia. Weight gain alone is not the goal: without a resistance training and protein stimulus, regained mass is likely to be fat rather than functional muscle.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Anti-GDF-15 therapy combined with supervised resistance exercise and protein supplementation produces greater gains in lean mass and physical function than the antibody alone, at equal total weight gain.
- Rationale: Anabolic signals are needed to direct nutrient partitioning into muscle, as shown by decades of sarcopenia and geriatric rehabilitation research. Function, not weight, is what determines whether patients can tolerate treatment and live independently.
- Proposed test: A factorial randomised trial of antibody with or without a structured exercise and nutrition programme, with lean mass by imaging and a physical function measure as co-primary endpoints.
- Maturity: early-clinical
- Actor: industry

## Sources

- Cachexia (overview): https://en.wikipedia.org/wiki/Cachexia

## Connected records

- ideas: [Structured exercise prescribed like a drug in all curative-intent cancer care](https://onco.cc/ideas/idea-exercise-as-adjuvant/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [Exercise & lifestyle oncology](https://onco.cc/technologies/exercise-oncology/), [Monoclonal antibodies](https://onco.cc/technologies/monoclonal-antibody/), [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/)
- bottlenecks: [Cachexia, toxicity and the limits of the patient](https://onco.cc/bottlenecks/b-cachexia-supportive/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- key papers: [CHALLENGE: a structured exercise programme after chemotherapy improves survival in colon cancer](https://onco.cc/key-papers/paper-challenge-exercise-nejm-2025/)
- trials: [Ponsegromab phase 2 in cancer cachexia](https://onco.cc/trials/ponsegromab-phase-2/)
- roadmaps: [Diet, exercise and lifestyle roadmap: causes established → interventions that disappointed → exercise proven as treatment](https://onco.cc/roadmaps/nutrition-lifestyle-roadmap/)

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