Phase 2 RCT: Ponsegromab Shows Promise for the Treatment of Cancer Cachexia
23 Sep, 2024 | 21:48h | UTCBackground: Cancer cachexia is a multifactorial syndrome characterized by weight loss, muscle wasting, and reduced quality of life. Elevated levels of growth differentiation factor 15 (GDF-15), a cytokine, have been associated with cachexia. Ponsegromab, a monoclonal antibody that inhibits GDF-15, has shown potential in reversing cachexia in early studies by improving weight, appetite, and physical activity. This phase 2, randomized, double-blind trial aimed to assess the efficacy and safety of ponsegromab in patients with cancer cachexia and elevated GDF-15 levels.
Objective: To evaluate the impact of ponsegromab on body weight, cachexia symptoms, appetite, physical activity, and safety in cancer cachexia patients with elevated GDF-15 levels.
Methods: In this 12-week study, 187 patients with non-small-cell lung cancer, pancreatic cancer, or colorectal cancer and elevated GDF-15 levels (≥1500 pg/mL) were randomized into four groups: ponsegromab 100 mg, 200 mg, 400 mg, or placebo, administered subcutaneously every four weeks. The primary endpoint was the change in body weight from baseline to week 12. Secondary outcomes included appetite and cachexia symptoms, physical activity measured via digital devices, and safety. The trial also included exploratory endpoints like changes in skeletal muscle mass.
Results:
At 12 weeks, patients treated with ponsegromab showed significant weight gain compared to placebo. The median weight gain differences were 1.22 kg in the 100-mg group, 1.92 kg in the 200-mg group, and 2.81 kg in the 400-mg group. Significant improvements in appetite and cachexia symptoms were observed in the 400-mg group compared to placebo. Physical activity, measured by nonsedentary time, also increased by 72 minutes per day in the 400-mg group. Adverse events were reported by 70% of ponsegromab patients and 80% of placebo patients. Serious adverse events occurred at similar rates across groups, but none were deemed related to treatment. No significant safety concerns were identified.
Conclusions: Ponsegromab effectively increased body weight and improved cachexia symptoms in patients with cancer cachexia and elevated GDF-15 levels, supporting GDF-15’s role as a key driver of cachexia. The findings suggest that ponsegromab may be a promising therapeutic option for managing cancer cachexia, with a favorable safety profile.
Implications for Practice: Ponsegromab could represent a targeted therapy for cancer cachexia, addressing weight loss, appetite, and physical function. Clinicians may consider its use for patients with advanced cancers experiencing cachexia, particularly those with elevated GDF-15 levels.
Study Strengths and Limitations: Strengths of the study include its randomized, double-blind design and the use of objective measures such as digital physical activity tracking. Limitations include the relatively short trial duration, and missing physical activity data for some patients. Additionally, the efficacy of ponsegromab across different baseline levels of GDF-15 requires further investigation.
Future Research: Larger and longer-term trials are necessary to confirm the therapeutic benefit of ponsegromab in cancer cachexia. Future research should explore its impact on survival and assess whether GDF-15 inhibition benefits other conditions associated with elevated GDF-15, such as heart failure and chronic kidney disease.