Ponsegromab Could Offer Further Treatment for Cancer Cachexia

Presented at the European Society for Medical Oncology (ESMO) 2024 Congress, Pfizer announced results from its phase 2 study that assessed ponsegromab, a monoclonal antibody directed against growth differentiation factor-15 (GDF015). The treatment met the primary end point of change from baseline body weight among individuals with cancer cachexia and elevated levels of GDF-15.¹

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Cachexia is a common, life-threatening wasting condition that often impacts quality of life among individuals diagnosed with cancer. The metabolic condition is estimated to occur in about 9 million individuals globally. Individuals with cachexia can experience symptoms such as weight and muscle loss, along with an inability to tolerate treatment for chronic conditions like cancer and heart failure. Research has shown that cachexia can decrease cancer survival rates and is connected to 30% of all cancer-related deaths.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 Jeffrey Crawford, MD, George Barth Geller Professor for Research at Duke Cancer Institute and principal investigator, in a news release.¹

Ponsegromab is an investigational monoclonal designed to treat cachexia by targeting GDF-15. The study authors noted that a previous phase 1b trial displayed good tolerability of ponsegromab as it suppressed serum GDF-15 concentrations among individuals with cancer cachexia.³

“Discovered and developed in-house at Pfizer, ponsegromab represents our ability to translate deep scientific expertise into patient benefit,” said Charlotte Allerton, head of discovery and early development at Pfizer, in a news release.¹

The current randomized, double-blind, placebo-controlled phase 2 study (NCT05546476) evaluated the effect of ponsegromab on body weight among individuals with non-small cell lung cancer (NSCLC), pancreatic cancer, or colorectal cancer cachexia, who also had elevated serum GDF-15 concentrations. The study included 187 individuals who were randomly assigned to receive ponsegromab (100 mg, 200 mg or 400 mg) or a placebo once every 4 weeks subcutaneously for 12 weeks, according to study authors.¹

Ponsegromab displayed significant and robust increase in body weight at the completion of the study for all doses, compared with the placebo—2.02% (95% confidence interval (CI), -0.97 to 5.01%) in the 100 mg treatment group, 3.48% (95% CI, 0.54 to 6.42%) in the 200 mg group, and 5.61% (95% CI, 2.56 to 8.67%) in the 400 mg group. Additionally, individuals who received the 400 mg dose displayed improvements in appetite, physical activity, and skeletal muscle index.¹

“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,” said Crawford, in a news release.¹

Adverse events were reported in 7.7% of individuals treated with ponsegromab compared with 8.9% in the placebo group, although the study authors noted that none were clinically significant.¹

“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,” Allerton said in the news release.¹

REFERENCES

1. Pfizer Presents Positive Data from Phase 2 Study of Ponsegromab in Patients with Cancer Cachexia. Pfizer. News release. September 14, 2024. Accessed September 20, 2024. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-presents-positive-data-phase-2-study-ponsegromab.

2. Differential Diagnosis of Cachexia and Refractory Cachexia and the Impact of Appropriate Nutritional Intervention for Cachexia on Survival in Terminal Cancer Patients. Nutrients. News release. March 13, 2021. Accessed September 20, 2024. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000003/#:~:text=Refractory%20cachexia%20is%20defined%20as,months.

3. A Phase Ib First-In-Patient Study Assessing the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ponsegromab in Participants with Cancer and Cachexia. AACR. News release. February 1, 2024. Accessed September 20, 2024. https://aacrjournals.org/clincancerres/article/30/3/489/733546.