Pfizer Shares Positive Phase 2 Results for Ponsegromab in Cancer Cachexia

Pfizer Inc. (NYSE: PFE) has shared promising 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's primary goal was to evaluate the change in body weight from baseline in patients with cancer cachexia and elevated GDF-15 levels. Cachexia is a severe, life-threatening wasting condition that significantly affects the quality of life in cancer patients.

The results, which were unveiled at the European Society for Medical Oncology (ESMO) 2024 Congress and published in The New England Journal of Medicine, demonstrated that ponsegromab met its primary endpoint. "Cachexia is common among cancer patients, leading to weight loss, functional decline, and adverse outcomes. Despite its prevalence, no treatments are currently available," said Dr. Jeffrey Crawford, the principal investigator and George Barth Geller Professor for Research at Duke Cancer Institute. He noted that patients receiving ponsegromab showed improvements in body weight, muscle mass, quality of life, and physical function, suggesting a potential breakthrough treatment for cachexia.

The Phase 2 study involved 187 participants with non-small cell lung cancer, pancreatic cancer, or colorectal cancer. Ponsegromab showed significant increases in body weight after 12 weeks for all doses: 2.02% in the 100 mg group, 3.48% in the 200 mg group, and 5.61% in the 400 mg group, compared to placebo. The 400 mg group also showed improvements in appetite, physical activity, and skeletal muscle index. No significant adverse trends were noted, with adverse events occurring in 7.7% of patients taking ponsegromab compared to 8.9% of patients on placebo.

Charlotte Allerton, Head of Discovery and Early Development at Pfizer, emphasized that ponsegromab's development showcases Pfizer's ability to translate scientific expertise into patient benefits. She stated that the results provide strong evidence that targeting GDF-15 can interrupt the mechanisms driving cachexia, potentially benefiting patients with cancer cachexia and other severe conditions. Pfizer is now in discussions with regulators to plan late-stage development, aiming to start registration-enabling studies in 2025. The company is also investigating ponsegromab in a Phase 2 study for heart failure patients with elevated GDF-15 levels.

The Phase 2 trial's primary objective was to assess ponsegromab's effect on body weight in patients with cancer cachexia and elevated GDF-15 levels. Secondary and exploratory objectives included changes in appetite, cachexia symptoms, physical activity, and skeletal muscle index. Participants received ponsegromab or placebo once every four weeks for 12 weeks.

Cachexia affects approximately 9 million people globally and is characterized by weight and muscle loss, which can impair patients' ability to tolerate treatments for underlying chronic diseases like cancer and heart failure. In cancer, cachexia can reduce the efficacy of treatments and contribute to decreased survival rates, potentially causing up to 30% of cancer-related deaths. Despite its severity, there are no FDA-approved treatments for cachexia.

Ponsegromab is an investigational monoclonal antibody designed to treat cachexia by targeting GDF-15. Prior Phase 1b data showed robust suppression of unbound circulating GDF-15 levels in participants with cancer cachexia, along with promising efficacy signals, including increases in body weight and patient-reported outcomes.

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