Ponsegromab helped patients with cachexia and elevated GDF-15 levels gain weight, increase activity and improve cachexia symptoms, with manageable safety.
The inhibition of GDF-15 with ponsegromab demonstrated increased weight gain and overall activity level and reduced cachexia symptoms for patients with cachexia and elevated GDF-15 levels.
According to findings published in The New England Journal of Medicine, “these findings support the hypothesis that GDF-15 is a primary driver of cachexia and establish this cytokine as a potential therapeutic target for further evaluation in clinical trials,” study authors wrote.
Patients were to receive a ponsegromab dose of 100 mg (46 patients), 200 mg (46 patients), 400 mg (50 patients) or to receive placebo (45 patients). Treatment was administered subcutaneously every four weeks for three doses. A total of 37% of patients were women, 62% were White and 37% were Asian, with an underrepresentation of Black patients.
After 12 weeks, patients treated with ponsegromab showed significantly greater weight than those treated with a placebo. Specifically, the median between-group difference was 1.22 kilograms (kg) in the 100 milligram (mg) group, 1.92 kg in the 200 mg group and 2.81 kg in the 400 mg group. Measures of appetite and cachexia were improved, along with physical activity, in the 400 mg ponsegromab group relative to the placebo.
Cachexia: a condition of severe muscle wasting and weight loss.
GDF-15: a protein linked to inflammation and tissue damage.
Hypokalemia: a condition of low potassium in the blood.
Pyrexia: another term for fever.
Cytokine: signaling molecules released by cells to communicate with other cells.
Subcutaneously: under the skin.
Regarding safety, the most common side effects included diarrhea, cancer progression, anemia, hypokalemia, nausea, vomiting and pyrexia. Side effects of any severity occurred in 70% of patients in the treatment group and in 80% of those in the placebo group. Patients treated with the placebo experienced higher rates of diarrhea, nausea and vomiting. Side effects that were considered related to ponsegromab or placebo were reported in 4% to 11% of patients in the ponsegromab groups, while 9% of patients in the placebo group experienced similar events. Most of these side effects (88%) were classified as mild to moderate in severity.
“All ponsegromab doses were considered to be safe and had a side-effect profile similar to that of placebo,” study authors wrote.
During the trial period, 26 patients died. Six deaths occurred in each of the 100 mg and 200 mg ponsegromab groups, nine in the 400 mg ponsegromab group and five in the placebo group. No deaths were deemed trial related. The most common cause of death was disease progression (16 patients), followed by adverse events (10 patients)
Among a total of 187 patients, at a mean age of 67 years, 74 had non-small-cell lung cancer, 59 had pancreatic cancer and 54 had colorectal cancer. The median weight of patients was 54.8 kg. Patients that were excluded included those with cachexia caused by a nonmalignant illness, planned surgery and the use of drugs prescribed to increase weight or appetite.
“Eligibility criteria permitted the enrollment of patients across three cancer types who were receiving any type or line of cancer treatment. The benefit of ponsegromab over placebo with respect to body weight was observed across all three cancer types,” study authors wrote. “These results provide the first conclusive demonstration that GDF-15 is a common driver of cachexia across different malignant solid tumors, thereby establishing GDF-15 as a therapeutic target.”
Reference:
“Ponsegromab for the Treatment of Cancer Cachexia” by Dr. John D, Groarke, et al., The New England Journal of Medicine.
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