Patients on the highest dose of Pfizer’s ponsegromab gained 4.6% of their body weight after 12 weeks. The antibody, which blocks a protein called GDF-15, was tested in people with cachexia, a life-threatening wasting syndrome that has no approved drug treatment.
The mid-stage results were presented at the ESMO congress in Barcelona, and the New England Journal of Medicine published them at the same time. Pharmaphorum reported that the weight gain reached 5.6% at the most effective dose, above the 5% mark considered clinically meaningful. Pfizer is now weighing a phase 3 program for next year.
What the trial found
The phase 2 study enrolled 187 patients whose cachexia was linked to lung, pancreatic or colorectal cancer. At 100mg, weight rose 2.2%. At 200mg the gain was 3.48%, and at 400mg it was 4.6%. At the top dose, patients also showed better appetite, fewer cachexia symptoms, more physical activity and more muscle mass.
The drug was generally well tolerated. Adverse events of any kind were reported by 70% of patients on ponsegromab and 80% of those on placebo.
Pfizer had earlier shown that the drug lowers circulating GDF-15 in the blood, a protein known to run high in cachexia.
“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,” said Charlotte Allerton, Pfizer’s head of discovery and early development.
Why the syndrome matters
Cachexia strips away muscle and fat, and it often comes with insulin resistance and anorexia. It seems to have an inflammatory component. Current care relies on nutritional support, appetite stimulants, anti-inflammatories and physical rehabilitation, and life expectancy can drop sharply once patients stop responding to treatment.
The condition affects about 9 million people worldwide. It also occurs with chronic kidney disease, HIV and multiple sclerosis. According to Pfizer, 80% of cancer patients who develop it die within one year of diagnosis, and it accounts for around a third of all cancer deaths.
Ponsegromab is also being tested in a phase 2 study of patients with heart failure and elevated serum GDF-15.
