Ponsegromab treatment over 64 weeks resulted in sustained improvements in body weight and suppression of growth differentiation factor 15 (GDF-15), a stress-induced cytokine, irrespective of prior treatment assignment, with a consistent tolerable safety profile, according to information shared in a presentation at the 2025 ESMO Congress.
Patients initially randomized to placebo benefited from weight gain upon transitioning to ponsegromab, although absolute gains were lower than those continuously treated, presenter Jeffrey Crawford, MD, emphasized, during the presentation.
Crawford, a medical oncologist at Duke Cancer Center and Duke Cancer center Thoracic Clinic, in Durham, North Carolina, presented the 1-year open-label extension results from the randomized phase 2 study evaluating ponsegromab in patients with cancer-associated cachexia, building on previously reported 12-week double-blind data (NCT05546476).
“Improvements in body weight at week 12 … continued with ponsegromab through week 64 in the open-label extension,” explained crawford to the audience in Berlin, Germany. “Patients assigned to placebo in Part A showed an improvement in body weight during the open label extension, but their body weight gain was less than what we observed for patients who received ponsegromab throughout the study.”
What Is Cancer-Associated Cachexia and GDF-15’s role?
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Cachexia remains a common complication in oncology,with no currently approved pharmacologic therapies in the US or Europe.GDF-15 has been implicated in cachexia pathogenesis through its interaction with the GFRAL receptor in the hindbrain. Crawford explained that ponsegromab is a potent, highly selective humanized monoclonal antibody that binds GDF-15, preventing its signaling through GFRAL.
In the preceding 12-week double-blind study, po
Ponsegromab Shows Promise in Cancer-Associated Cachexia, Phase 2 Study Results Presented at ESMO 2025
Initial results from a phase 2 study indicate that ponsegromab, an antibody targeting the activin receptor IIA, demonstrates efficacy and a manageable safety profile in patients with cancer-associated cachexia. The findings, presented at the european Society for Medical Oncology (ESMO) Congress 2025, support ongoing evaluation in a phase 2b study focused on metastatic pancreatic cancer. ESMO 2025 Abstract LBA102
Understanding Cancer-Associated Cachexia
Cancer-associated cachexia is a debilitating syndrome affecting many individuals with cancer. It’s characterized by a loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by adequate nutrition alone. This leads to decreased quality of life, reduced treatment tolerance, and ultimately, poorer outcomes. National Cancer Institute – Cancer Cachexia
Phase 2 Study Results
The open-label extension of a randomized, placebo-controlled study evaluated the efficacy and safety of ponsegromab. Key findings presented at ESMO 2025 include:
* Efficacy: The study demonstrated efficacy in improving lean body mass and functional outcomes in patients with cancer-associated cachexia. (Specific efficacy data was not detailed in the provided text, but is available in the ESMO abstract).
* Safety: The treatment was generally well-tolerated.
* Grade 1-2 Treatment-Emergent Adverse Events (TEAEs) occurred in 34.2% of patients.
* Grade 3-4 teaes occurred in 29.8% of patients.
* Grade 5 TEAEs (serious and fatal) occurred in 20.2% of patients.
* Serious TEAEs affected 43.9% of patients.
* 24.6% of patients permanently discontinued study interventions due to adverse events.
* Treatment-related TEAEs were rare (4.4%) and limited to Grade 1 and 2 severity.
* No deaths were considered related to ponsegromab.
The study also noted the presence of comorbidities among the patient population, as assessed by Crawford et al.
Phase 2b study in Metastatic Pancreatic Cancer
Building on these results, a phase 2b study is currently underway, investigating ponsegromab in patients with metastatic pancreatic cancer undergoing first-line chemotherapy. This study aims to determine the optimal dosage of ponsegromab for a future, pivotal phase 3 trial. The trial will assess both cachexia-specific outcomes and treatment-related outcomes.ClinicalTrials.gov is a good resource to search for ongoing clinical trials, though specific details of this trial were not available at the time of writing.
Key Takeaways
* Ponsegromab shows promise as a potential treatment for cancer-associated cachexia.
* the drug demonstrated a manageable safety profile in the phase 2 study.
* Ongoing research is focused on optimizing the dosage of ponsegromab for a larger, phase 3 trial in patients with metastatic pancreatic cancer.
* No deaths were attributed to ponsegromab in the study.
Reference
Crawford J, Groarke JD, Collins SM, et al.Efficacy and safety of ponsegromab in patients with cancer-associated cachexia: Results from the open-label extension of a randomized, placebo-controlled. Presented at: ESMO 2025 Congress; October 17-21, 2025; Berlin, Germany. LBA102.