Pfizer's investigational drug, ponsegromab, a Growth/Differentiation Factor 15 (GDF-15)-targeting monoclonal antibody, has shown promising results in a Phase II clinical trial for cancer cachexia, a wasting syndrome characterized by weight and muscle mass loss. The trial data, presented at the 2024 European Society of Medical Oncology (ESMO) meeting in Barcelona, indicated that ponsegromab led to clinically meaningful weight gain in patients with non-small cell lung cancer (NSCLC), pancreatic cancer, or colorectal cancer suffering from cachexia. Pfizer aims to start a pivotal program in 2025.
The double-blind Phase II trial (NCT05546476) involved 187 patients with cancer cachexia and elevated serum GDF-15 concentrations. Patients were divided into several dose groups to evaluate the effect of ponsegromab. After 12 weeks, the study found that patients in the 100mg dose group achieved a mean weight increase of 2.2%, the 200mg group 3.48%, and the 400mg group 5.6%. The drug was generally well-tolerated across all dose groups.
Clinical Significance of Weight Gain
The 5.6% mean weight increase observed in the 400mg dose group is particularly noteworthy. According to Charlotte Allerton, Pfizer’s Head of Discovery and Early Development, the Cancer Cachexia Endpoints Working Group has suggested that a weight gain of 5% is a clinically meaningful difference. These results, also published in the New England Journal of Medicine, suggest that ponsegromab could potentially address a critical driver of cachexia by targeting GDF-15.
Addressing an Unmet Need
Cachexia is a significant concern in cancer care, with no FDA-approved treatments currently available. The current standard of care involves feeding tubes or intravenous nutrition, nutritional supplements, and anti-inflammatory medications. The lack of targeted therapies highlights the urgent need for effective interventions like ponsegromab.
Future Development
Pfizer is in discussions with regulatory authorities 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 application in cardiometabolic conditions.
Broader Context
According to GlobalData’s Clinical Trials database, there are currently 138 trials underway addressing cachexia, indicating a significant research interest in this area. Pfizer's advancement of ponsegromab represents a notable step forward in the development of targeted therapies for this debilitating condition.
