Ponsegromab Significantly Improves Body Weight in Patients with Cancer Cachexia

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Data from Pfizer’s Phase II study of ponsegromab found that the treatment significantly improved body weight and muscle function in patients with cancer cachexia. Results from the trial published in The New England Journal of Medicine were also showcased as a late-breaking Proffered Paper Presentation at the European Society for Medical Oncology 2024 Congress. The data demonstrated that ponsegromab significantly improved body weight in patients with non-small cell lung cancer (NSCLC), pancreatic cancer, or colorectal cancer after 12 weeks of treatment.¹

“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 principal trial investigator Jeffrey Crawford, MD, George Barth Geller Professor for Research, Duke Cancer Institute, in a press release. “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.”

Pfizer’s Phase II study on ponsegromab included 187 patients with NSCLC, pancreatic cancer, or colorectal cancer. The primary endpoint of the study was to assess the effect of ponsegromab on body weight in patients with cancer cachexia and elevated serum GDF-15 concentrations. Secondary endpoints included change from baseline in appetite and cachexia symptoms, digital measures of physical activity, and changes in lumbar skeletal muscle index. Patients were randomly assigned to receive ponsegromab (100 mg, 200 mg, or 400 mg) or placebo once every four weeks subcutaneously for 12 weeks.

Results show that after 12 weeks of treatment, patients in the 400 mg group experienced a 5.61% weight gain and improvements in in appetite, physical activity, muscle mass, and overall symptoms.

Treatment-related adverse events (AEs) were reported by 7.7% of patients in the ponsegromab cohort compared to 8.9% in the placebo group. There were no clinically significant AEs associated with ponsegromab administration.¹

According to a study published in The European Journal of Cancer Care, approximately 80% of cancer patients in the US develop cancer cachexia, with 20% dying as a result of cachexia syndrome. In Europe, 90% of cancer patients are at risk for developing cachexia, with 30% of those at risk eventually contracting it. Globally, studies have found that male patients tend to experience greater weight loss, muscle wasting, reduction of grip strength, and loss of functionality compared to female patients. The study also suggested that patients with cachexia have the option of diet and exercise along with treatment.²

“Discovered and developed in-house at Pfizer, ponsegromab represents our ability to translate deep scientific expertise into patient benefit,” said Charlotte Allerton, head, discovery and early development, Pfizer, in the press release. “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. We look forward to advancing this program as part of our broader cardiometabolic portfolio to address weight management across the spectrum of patient need.”

Moving forward, Pfizer intends to initiate development plans with regulators with the goal of starting registration-enabling studies in 2025. Additionally, the medication is currently being studied in patients with heart failure and elevated serum GDF-15 concentrations in another Phase II study.¹

References

1. Pfizer Presents Positive Data from Phase 2 Study of Ponsegromab in Patients with Cancer Cachexia. Pfizer. September 14, 2024. Accessed September 16, 2024. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-presents-positive-data-phase-2-study-ponsegromab

2. Prevalence of Cachexia in Cancer Patients. Willey. July 29, 2023. Accessed September 16, 2024. https://onlinelibrary.wiley.com/doi/10.1155/2023/5743872#:~:text=In%20the%20United%20States%2C%20reports,syndrome%20%5B7%E2%80%939%5D.