Pfizer's investigational drug, ponsegromab, has shown promising results in a Phase II clinical trial for cancer cachexia, demonstrating clinically meaningful weight gain in patients. The company plans to initiate pivotal studies in 2025, marking a significant step forward in addressing this unmet medical need.
The double-blind Phase II trial (NCT05546476) evaluated ponsegromab in 187 patients with non-small cell lung cancer (NSCLC), pancreatic cancer, or colorectal cancer who were suffering from cachexia and had elevated serum Growth/Differentiation Factor 15 (GDF-15) concentrations. The study included several dose groups to assess the drug's efficacy and safety.
Weight Gain Results
After 12 weeks of treatment, patients receiving ponsegromab experienced mean weight increases of 2.2% in the 100mg dose group, 3.48% in the 200mg group, and 5.6% in the 400mg group. The drug was generally well-tolerated across all dose groups. The 5.6% weight gain in the highest dose group is particularly noteworthy, as it exceeds the 5% threshold recently suggested by the Cancer Cachexia Endpoints Working Group as a clinically meaningful difference.
Targeting GDF-15
Ponsegromab is a monoclonal antibody that targets GDF-15, a protein implicated in the development of cachexia. By inhibiting GDF-15, ponsegromab aims to interrupt a critical driver of muscle wasting and weight loss associated with cancer cachexia. Pfizer previously published Phase Ib data demonstrating ponsegromab's ability to suppress unbound circulating GDF-15 levels in cancer cachexia patients.
Expert Commentary
Charlotte Allerton, Head of Discovery and Early Development at Pfizer, stated, "These results provide strong evidence that we have unlocked a mechanism to interrupt a critical driver of cachexia, GDF-15, which has the potential to impact patients with cancer cachexia and other life-threatening conditions." She added that Pfizer looks forward to advancing the program as part of its broader cardiometabolic portfolio to address weight management across the spectrum of patient need.
Cachexia and Current Treatment Landscape
Cachexia, also known as wasting syndrome, is characterized by the loss of weight and muscle mass. It commonly affects cancer patients and currently lacks FDA-approved treatment options. The current standard of care includes feeding tubes or intravenous nutrition, nutritional supplements, and anti-inflammatory medications, which often provide limited relief.
Future Plans
Pfizer is currently in discussions with regulatory agencies regarding late-stage development plans, with the goal of initiating registration-enabling studies in 2025. The company is also investigating ponsegromab in a Phase II study for patients with heart failure (HF) and elevated serum GDF-15 concentrations (NCT05492500), expanding its potential applications.
