Could a Drug in Clinical Trials Mean Breakthrough in Cancer Cachexia Treatment?

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Cancer cachexia is a devastating condition that affects up to 80% of cancer patients, according to the National Cancer Institute, particularly those with advanced stages of lung, pancreatic, colorectal, and other cancers. Characterized by significant weight loss, muscle wasting, extreme weakness, and fatigue, cachexia can severely impact quality of life and reduce the effectiveness of cancer treatments. It is even linked to an increased risk of death in cancer patients, contributing to up to 30% of cancer-related fatalities

Yet, until recently, there have been very few treatment options to address this condition, despite how commonly it is experienced by patients with cancer, and there are no approved treatments in the United States. In 2020, an American Society of Clinical Oncology committee issued the first professional guidelines on managing cachexia.

Now, it’s possible hope may be on the horizon, thanks to an experimental drug called ponsegromab. 

In Phase 2 clinical trials, ponsegromab has shown promising results in treating cancer cachexia, offering new hope for patients who have long struggled with this debilitating syndrome.

Ponsegromab is a type of treatment called a monoclonal antibody. These antibodies are designed in the laboratory to specifically bind to certain targets in the body, such as antigens on the surface of cancer cells. 

How ponsegromab works

In this case, ponsegromab was designed to target and bind to a protein called GDF-15 (growth differentiation factor 15), which has been found to play a crucial role in the development of cachexia. Research has shown that the GDF-15 protein is abundant in the blood of people with cachexia and is not just a marker of the condition, but an active driver. 

In the brain, GDF-15 binds to a receptor called GFRAL, which plays a key role in regulating appetite and energy balance. By using ponsegromab to target and block GDF-15 from binding with GFRAL, it aims to reduce the muscle and fat loss that defines cachexia, ultimately helping patients regain weight and improve their overall well-being.

In a recent Phase 2 clinical trial, nearly 200 patients with advanced cancer and cachexia were randomly assigned to receive different doses of ponsegromab or a placebo and the results were encouraging. Those treated with ponsegromab gained an average of 2 to 6 pounds over a 12-week period, depending on the dose. During the same period, placebo recipients lost an average of just one pound. 

A summary of the study from the NCI notes that those who received the highest dose of ponsegromab not only resulted in significant weight gain, but also said they experienced improvements in appetite, fewer cachexia-related symptoms, and increased physical activity compared to those in the placebo group. Importantly, the drug caused very few side effects, with a similar incidence of adverse events in both the ponsegromab and placebo groups, suggesting that it is well-tolerated.

For patients with cancer cachexia, who often experience a rapid decline in health, this new treatment offers a potentially life-changing option. Beyond improving quality of life, ponsegromab may also help patients better tolerate cancer therapies, potentially improving overall survival outcomes.

The positive Phase 2 results have generated excitement within the cancer research community. Ponsegromab is currently the most advanced drug in clinical development targeting GDF-15, and Pfizer, which manufactures the drug, plans to expand the trial with larger studies in 2025. 

If these studies continue to demonstrate efficacy and safety, ponsegromab could be one step closer to FDA approval, marking a major breakthrough in the treatment of cancer cachexia.

Hope on the horizon, but more research needed

A few more possible treatment options for cachexia are under investigation, but thus far, ponsegromab is the only to have reached this phase in clinical trials.

While the Phase 2 results are promising, more research is needed to fully understand the role of GDF-15 in cachexia across different cancer types. Experts emphasize that more studies are required to determine the optimal dose of ponsegromab and its long-term safety. Nevertheless, the progress made so far represents a hopeful step toward addressing an urgent unmet medical need.

Cachexia has long been a challenge for both patients and healthcare providers, but with the promising results from Phase 2 trials of ponsegromab, we may be on the cusp of an exciting new treatment for this condition. As research continues and larger trials move forward, ponsegromab could become a key weapon in the fight against cancer cachexia, helping patients gain weight, improve their strength, and enhance their quality of life during one of the most difficult periods of their cancer journey.

Learn more: What are clinical research phases, and what do they mean?

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