My Childhood Friend’s Illness Defined My Life’s Work: To Find a Cure for Cachexia

One of my treasured childhood photographs shows my kindergarten class, with about twenty small children sitting on the grass near a lake. I was the unruly kid with sun-bleached hair sitting on the right side of the front row.? Next to me sat my best friend who shared my love for roaming the thousands of acres of game refuge where we both lived. We were close, far more similar to siblings than friends. As we approached high school graduation many years later, he started to feel sick all the time and lose weight. Ultimately, he was diagnosed with a deadly bone cancer that took his life after just six months. Without question, watching my friend waste away from his cancer, a condition I later learned is called cachexia (pronounced ka-kex-ee-a, from the Greek roots for “bad condition”), planted the seeds of determination that would define the rest of my career.?

As a physician, I have seen the devastating impact of cachexia on patients and their families and felt their frustration at having no effective treatment.? Cachexia is not only at the root of weakness and misery, but also the primary cause of death in many chronic diseases. This condition is most obvious in people with cancer, but also impacts people with chronic lung diseases, heart failure, chronic infections, and chronic kidney disease. In every case, weakness, fatigue, and loss of appetite are common features.?

Those suffering from cachexia primarily lose muscle rather than fat, the opposite of what is seen with dieting and starvation. This involuntary weight loss is accompanied by a loss of appetite and cannot be cured by increasing nutrition (e.g., with a feeding tube).??

It has been nearly forty years since my friend died, but the options for people with cachexia remain limited.?Certainly, improving nutrition and doing everything possible to maintain physical fitness will help prevent muscle loss and all of the other associated problems with cachexia.? However, there are no currently approved drugs that effectively prevent or treat cachexia in people with chronic diseases.? But there is hope.? The centers in the brain that respond to systemic illness signals and produce the sickness response are now defined, and we can now use that knowledge to design new treatments based on these fundamental discoveries in neuroscience. Furthermore, we can combine these new discoveries with new insights into how the brain regulates the function of peripheral organs to design drugs that will prevent or treat cachexia without causing significant side-effects. It is with this goal in mind that I helped to found Endevica Bio – where I am Chief Medical and Scientific Officer -- to create and test novel treatments for cachexia.?

Fortunately, we have made rapid progress developing a drug. After extensive safety testing, we took our lead candidate into a phase 1 clinical trial in healthy volunteers. Our drug proved not only very safe, but also increased caloric intake and the desire for food.? The next challenge we faced was to convince regulators that we should be allowed to give this drug to people soon after they’re diagnosed with cancer rather than waiting until the patients were extremely sick.? To accomplish this, we first demonstrated that our drug was extremely effective in preventing weight loss not just from cancer, but also from its treatment. When our drug was given with multiple different kinds of chemotherapy, it prevented weight loss and improved appetite even during high-dose chemotherapy.? Second, we once again took advantage of new knowledge about the relationship between body weight and cancer survival. These new findings show that people who are relatively lean at diagnosis, and those that lose weight during treatment, have poor outcomes relative to those who begin at higher weights and do not lose weight during treatment. This observation strongly argued that optimization of body weight and prevention of weight loss will improve quality of life and survival rates in patients with cancer. We plan to initiate our phase 2 clinical trials in patients with cancer by the end of this year.?

Ultimately, my personal goal is to utilize fundamental discoveries regarding brain function to prevent and treat human misery. While improved survival is always a goal, we believe that we can improve the quality of life in patients with chronic illness, and allow these patients to remain productive and strong for the duration of their illness and treatment. While weight and appetite are important parts of our lead drug program, we have our sights set on treating fatigue, cognitive problems, and chronic pain that are unfortunately common for patients with both acute and chronic diseases. Inventing and developing these novel treatments is a core principle of our company and will ultimately allow me to realize the dream of translating decades of scientific discovery into meaningful clinical therapeutics.?

?