Forging New Pathways to Treat Unintentional Weight Loss

Researchers are working to find solutions for people with both cancer and cachexia, a serious metabolic condition

Patients living with certain chronic illnesses, such as cancer, congestive heart failure, or chronic obstructive pulmonary disease (COPD), often develop a serious metabolic condition called cachexia, which can cause unintentional weight loss, loss of appetite, muscle wasting, and/or fatigue.1,2,3 This wasting disorder can severely impact patients’ quality of life and, in some cases, hinder their ability to continue treatment for their primary illness.3

For patients, the impact of cachexia on daily life is far-reaching. During a Cancer Support Community patient-focused drug development meeting(link is external) we sponsored in 2021, patients described the emotional and physical impacts of losing their appetites and later their ability to handle daily living tasks, such as getting out of bed and taking a shower. Caregivers also shared the challenges of watching loved ones go through this transformation.

These real-life insights from people affected by cachexia are helping scientists determine how to address the disease in a meaningful way. With patient input, our efforts are aimed at tackling multiple symptoms at once, understanding that improving appetite and reversing muscle wasting both play a critical role in improving quality of life.

“Novel science is emerging to increase our understanding of how these pathways interact with one another.”
Danna Breen, Ph.D., Associate Research Fellow

Our lead cachexia program focuses on a novel mechanism, growth differentiation factor-15 (GDF-15), a cellular signaling protein linked to appetite and energy regulation. Patients with late-stage illnesses, particularly cancer, have elevated levels of this signaling protein. It’s believed that GDF-15 interacts with receptors in the brain related to appetite control, causing loss of appetite and nausea.

In pre-clinical models, scientists have found that a GDF-15-blocking antibody could help restore appetite, improve body composition and promote weight gain in mice. While the research is still early, scientists hope these results could translate to cancer patients, who often need to limit their chemotherapy doses due to loss of body weight. “We’re either using one target with a lot of horsepower or multiple targets in combination that could treat multiple aspects of the disease,” said Danna Breen, Ph.D., an Associate Research Fellow in Pfizer’s Internal Medicine Research Unit.

Caregiver holding hands of patient, who is showing signs of muscle wasting

Cachexia, which can cause muscle wasting, occurs in the late stages of many chronic illnesses, including cancer.

Pfizer is currently conducting a Phase 1 study to better understand the safety, tolerability and pharmacological activity of an investigational GDF-15 antibody when administered to patients with cancer and cachexia.

Our scientists are also pursuing separate cachexia programs to combat other forms of anorexia and unintentional weight loss, which are designed to be complementary to the GDF-15 antibody. “Novel science is emerging to increase our understanding of how these pathways interact with one another,” said Breen. “Hopefully, this will lead us to identify the most effective therapies.”

With a patient-centered approach, researchers could potentially tailor cachexia treatment combinations based on patients’ needs. “We’re really hoping to improve patient quality of life,” added Breen.

  1. Lok C. Cachexia: The Last Illness. Nature. 2015;528:182-183.

  2. “Definition of Cachexia and Sarcopenia” Society of Sarcopenia, Cachexia and Wasting disorders. is external). Accessed December 6, 2021.

  3. “Tackling the Conundrum of Cachexia in Cancer.” National Cancer Institute. is external). Published November 1, 2011. Accessed December 6, 2021.