The Skinny on Ponsegromab for the Treatment of Cancer Cachexia

Although cancer cachexia affects more than half of patients and is associated with increased morbidity and mortality (J Cachexia Sarcopenia Muscle 2021; 12:1477), there are no current FDA-approved treatments. Growth differentiation factor 15 (GDF-15) is a cytokine involved in central modulation of cancer cachexia and is inhibited by the investigational monoclonal antibody ponsegromab. In this industry-sponsored, international, phase 2, double-blind trial, investigators randomized 187 adults (median age, 67 years) with cancer cachexia and elevated serum GDF-15 to receive 3 doses of 100, 200, or 400 mg of ponsegromab subcutaneously or placebo every 4 weeks. All had significant involuntary weight loss within the previous 6 months and a life expectancy of ≥4 months.

Participants had non–small-cell lung cancer, pancreatic cancer, or colorectal cancer; 90% were receiving systemic cancer-directed therapy; 62% were white and 37% were Asian. The median time from cancer diagnosis to randomization was 11.7 months. Nearly 75% completed the 12-week visit, with similar rates of early discontinuation across treatment groups. Receipt of palliative care was similar across groups.

At 12 weeks, all three ponsegromab groups had significantly greater weight gain — the primary endpoint — than the placebo group (between-group differences: 1.22 kg, 1.92, kg, and 2.81 kg in the 100-, 200-, and 400-mg groups, respectively). Changes were consistent with GDF-15 suppression. Among secondary endpoints, no appetite loss was reported in 39% of the 200-mg group, compared with 21% in the placebo group. Patients in the 400-mg group reported increased overall activity at 12 weeks compared with placebo. Adverse events were similar among groups.