Pfizer announced positive results from its Phase 2 study of ponsegromab, a monoclonal antibody targeting growth differentiation factor-15 (GDF-15), for the treatment of cancer cachexia. The study met its primary endpoint, showing a statistically significant increase in body weight compared to placebo in patients with cancer cachexia and elevated GDF-15 levels. The findings, presented at the European Society for Medical Oncology (ESMO) 2024 Congress and published in The New England Journal of Medicine, offer hope for a potential breakthrough treatment for this debilitating condition.
The Phase 2 trial (NCT05546476) involved 187 participants with non-small cell lung cancer, pancreatic cancer, or colorectal cancer, all suffering from cachexia. Patients received either ponsegromab (100 mg, 200 mg, or 400 mg) or placebo subcutaneously every four weeks for 12 weeks. The primary endpoint was the change from baseline in body weight.
Significant Weight Gain with Ponsegromab
Ponsegromab demonstrated significant increases in body weight across all doses. Specifically, the 400 mg group showed a 5.61% increase in body weight (95% CI, 2.56 to 8.67%) compared to placebo. The 100 mg and 200 mg groups also showed increases of 2.02% (95% CI, -0.97 to 5.01%) and 3.48% (95% CI, 0.54 to 6.42%), respectively.
Improvements in Cachexia Symptoms and Physical Activity
In addition to weight gain, patients in the 400 mg ponsegromab group experienced improvements in appetite, cachexia symptoms, physical activity, and skeletal muscle index. These improvements suggest a broader impact on the cachexia phenotype beyond just weight gain.
Safety and Tolerability
Ponsegromab was generally well-tolerated across all dose levels. Treatment-related adverse events occurred in 7.7% of patients taking ponsegromab, compared to 8.9% in the placebo group, indicating a favorable safety profile.
Expert Commentary
"Cachexia is a common condition in cancer patients, associated with weight loss, functional decline, and ultimately poor outcomes. Despite the number of people suffering from cachexia, there are no available options for us to help treat patients," said Jeffrey Crawford, M.D., George Barth Geller Professor for Research at Duke Cancer Institute, and principal investigator. "This study showed us those who received ponsegromab had improvement in body weight, muscle mass, quality of life, and physical function. These findings offer hope that a breakthrough targeted treatment is potentially on the horizon for our patients."
Future Development
Based on these promising Phase 2 results, Pfizer plans to discuss late-stage development plans with regulatory agencies and aims to initiate registration-enabling studies in 2025. Ponsegromab is also being evaluated in a Phase 2 study for patients with heart failure and elevated GDF-15 levels (NCT05492500).
About Cancer Cachexia
Cachexia is a complex metabolic condition affecting an estimated 9 million people worldwide. It is characterized by weight loss and muscle wasting, which can significantly reduce patients' ability to tolerate treatments for underlying chronic diseases like cancer and heart failure. In cancer patients, cachexia can diminish the efficacy of cancer treatments and contribute to decreased survival rates, accounting for up to 30% of cancer-related deaths. Currently, there are no FDA-approved treatments for cachexia, highlighting the unmet medical need in this area.
