GDF-15 inhibition with ponsegromab improved cancer cachexia symptoms: NEJM

A new study by John Groarke and team found the cachexia decreased when ponsegromab was administered at escalating dosages to patients with cancer cachexia and raised circulating growth differentiation factor 15 (GDF-15) levels. The findings of this study were published in the New England Journal of Medicine.

One frequent cancer consequence that is linked to a higher risk of mortality is cachexia. In cancer cachexia, there is an increase in the amount of the circulating cytokine growth differentiation factor 15. Ponsegromab is a humanized monoclonal antibody that inhibits GDF-15 and was linked to better weight, appetite, and physical activity in addition to decreased serum GDF-15 levels.

And so, individuals with cancer cachexia and a high serum GDF-15 level (≥1500 pg per milliliter) were randomized in a phase 2 randomized, double-blind, 12-week trial in a 1:1:1:1 ratio to either receive ponsegromab at a dose of 100 mg, 200 mg, or 400 mg subcutaneously every 4 weeks for three doses, or receive a placebo. The main outcome measure at 12 weeks was the shift in body weight from the baseline. Digital assessments of physical activity, safety, and symptoms of hunger and cachexia were important secondary end goals.

The randomization was performed on a total of 187 subjects. Of these individuals, colorectal cancer accounted for 29%, pancreatic cancer for 32%, and non-small-cell lung cancer for 40%. At 12 weeks, there was a significant difference in weight increase between the ponsegromab groups and the placebo group. The median between-group difference was 1.22 kg for the 100-mg group, 1.92 kg for the 200-mg group, and 2.81 kg for the 400-mg group. Measures of hunger, symptoms of cachexia, and physical activity all showed improvements in the 400-mg ponsegromab group when compared to placebo. 70% of the patients in the ponsegromab group and 80% of the individuals in the placebo group had adverse events of any kind. Overall, the inhibition of GDF-15 with ponsegromab led to enhanced gain in weight and general activity level and lowered cachexia symptoms among patients with cancer cachexia and raised GDF-15 levels.

Source:

Groarke, J. D., Crawford, J., Collins, S. M., Lubaczewski, S., Roeland, E. J., Naito, T., Hendifar, A. E., Fallon, M., Takayama, K., Asmis, T., Dunne, R. F., Karahanoglu, I., Northcott, C. A., Harrington, M. A., Rossulek, M., Qiu, R., & Saxena, A. R. (2024). Ponsegromab for the Treatment of Cancer Cachexia. In New England Journal of Medicine. Massachusetts Medical Society. https://doi.org/10.1056/nejmoa2409515