Cancer patients with wasting syndrome have gained weight after taking Pfizer’s anti-GDF-15 antibody in a midphase study, emboldening the Big Pharma to target a 2025 start date for its pivotal trial program.
Researchers estimate the wasting syndrome, known medically as cachexia, affects up to 80% of people with advanced cancer. As well as negatively affecting quality of life, the condition is thought to directly cause up to 30% of cancer deaths because muscle loss leads to heart or respiratory failure. GDF-15 is elevated in people with cachexia and high levels of the cytokine are associated with poor outcomes.
The evidence informed Pfizer’s decision to move its anti-GDF-15 antibody ponsegromab into a phase 2 trial in 2022. Saturday, the drugmaker reported the results at the European Society for Medical Oncology 2024 Congress and in The New England Journal of Medicine.
Pfizer compared three doses of ponsegromab to placebo in 187 people with non-small cell, pancreatic or colorectal cancer and elevated serum GDF-15 concentrations. Almost three-quarters of participants had stage 4 cancer.
After receiving a subcutaneous injection once every four weeks for 12 weeks, patients on the high dose had gained 3 kg more in body weight than their counterparts on placebo. Pfizer saw placebo-adjusted weight increases of 1.33 kg and 2.08 kg, respectively, at the low and middle dose. Patients on all doses of ponsegromab outperformed the placebo group from the fourth week of the trial.
The percentage weight gain on ponsegromab compared to placebo ranged from 2.02% at the low dose to 5.61% at the high dose. A spokesperson for Pfizer said the Cancer Cachexia Endpoints Working Group recently suggested weight gain of 5% as being clinically meaningful for patients with cancer-associated cachexia. Pfizer cleared that bar and generated other evidence the antibody could improve lives.
“The clinical relevance of the body weight increases observed in the patients in this study is augmented by the associated moderate improvements in appetite and cachexia symptoms and increased physical activity that were also observed in ponsegromab-treated patients, relative to placebo,” the spokesperson said. At the high dose, Pfizer saw significant improvements on measures of anorexia and activity, as well as in skeletal muscle.
Pfizer is now discussing the phase 3 program with regulatory authorities. The talks could help map out poorly charted territory. Talking at a Goldman Sachs event in 2023, NGM Biopharmaceuticals CEO David Woodhouse said the lack of a “proven path to follow” was a deterrent to studying the biotech's NGM120, which blocks the effects of GDF-15, in cachexia. Pfizer declined to comment on its expectations for the phase 3 design for ponsegromab.
Pfizer is also testing ponsegromab in heart failure patients with elevated serum GDF-15 concentrations in a phase 2 study. The trial, which is aiming to enroll more than 400 people, is scheduled to finish in 2025.