New drug proves effective in treating cancer-related wasting disease

CANCER DIGEST – Sept. 22, 2024 – An early study of a new drug has shown that it can successfully treat wasting disease, a common condition that often affects patients being treated for cancer, that results in weight loss, functional decline and poorer outcomes.

The drug ponsegromab is under development by Pfizer, which presented the study results at the European Society for Medical Oncology in Barcelona Spain, Sept. 13-17 along with simultaneous publication in the Sept. 14, 2024 New England Journal of Medicine.

Wasting disease, or cachexia (ku-KEK-see-uh), involves loss of appetite, weight loss, muscle wasting, fatigue and weakness. It affects more than 50 percent of cancer patients and often adversely affects patient outcomes. There are currently no FDA-approved treatments for it.

According to background information included in the NEJM article, cachexia is associated with the levels of a growth factor in the blood, called growth differentiation factor 15 (GDF-15) that affects appetite. The Pfizer researchers identified high levels of GDF-15 in the blood in cancer patients experiencing cachexia. Ponsegromab is an engineered monoclonal antibody that blocks GDF-15’s appetite suppression.

The Phase 2 study aimed at determining optimal effective dose was led by Pfizer’s John Groarke, MB, B.Ch, MPH, and Jeffrey Crawford, M.D. The study involved 187 cancer patients under treatment for non-small cell lung cancer, pancreatic cancer, and colorectal cancer. Patients were randomly assigned to three different doses of the drug ponsegromab, or placebo.

The drug was administered by injections every four weeks for 12 weeks at doses levels of 100mg, 200mg, 400mg, or placebo, no drug at all. Patients were weighed and tracked for 12 weeks. The results showed an median weight gain of 1.22 kilograms (2.65 pounds) more than the placebo group at the 100mg dose, 1.92kg (4.4lbs) more weight at the 200mg dose, and a median weight gain of 2.81kg (6.3lbs) in the 400mg group compared to the placebo group.

"Despite the number of people suffering from cachexia, there are no available options for us to help treat patients," Dr. Crawford, who is also a professor at Duke Cancer Institute, said 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."

Side effects were minimal and were reported by 80 percent of the people in the ponsegromab groups and 70 percent of the placebo group.

Based on the positive results, Pfizer is applying for clinical trials aimed at regulatory approval by the FDA.

The study was funded by Pfizer.

Sources: New England Journal of Medicine, and Pfizer press release