GDF-15 inhibition shows promise in cancer cachexia

The inhibition of GDF-15 with ponsegromab in patients with cancer cachexia helps promote weight gain, improve overall activity, and reduce symptoms, as shown in the results of a phase II study.

In the 12-week trial, 187 patients with cancer cachexia and an elevated serum GDF-15 level (≥1,500 pg/ml) were randomly assigned to receive ponsegromab at a dose of 100, 200, or 400 mg or to receive placebo. Treatment was administered subcutaneously every 4 weeks for a total of three doses.

The primary endpoint was the change from baseline in body weight at 12 weeks. Secondary endpoints included appetite and cachexia symptoms, digital measures of physical activity, and safety.

Of the patients, 40 percent had non–small-cell lung cancer, 32 percent had pancreatic cancer, and 29 percent had colorectal cancer. At week 12, weight gain was significantly greater for patients in the ponsegromab groups than for those in the placebo group. The median between-group difference was 1.22 kg (95 percent credible interval [CrI], 0.37–2.25) in the 100-mg group, 1.92 (95 percent CrI, 0.92–2.97) in the 200-mg group, and 2.81 (95 percent CrI, 1.55–4.08) in the 400-mg group.

Results for secondary outcomes showed improvements in measures of appetite and cachexia symptoms, as well as physical activity, in the 400-mg ponsegromab group vs the placebo.

Adverse events of any cause were documented in 70 percent of the patients in the ponsegromab groups and in 80 percent in the placebo group.