September 4, 2019

Novel treatment for Prader-Willi syndrome being tested at VUMC

A novel treatment for Prader-Willi syndrome, one of the most common genetic causes of obesity, may improve the insatiable hunger that patients with the disorder experience.

 

by Leigh MacMillan

F-O-O-D. Joe Bolander spelled out the word that equals trouble for people like him who have Prader-Willi syndrome (PWS), a complex genetic disorder that affects appetite, growth, metabolism, cognitive function and behavior.

Joe Bolander

“Food is the biggest challenge. It’s always around. I’m always thinking about it,” said Bolander, 39, as he sat on the edge of a bed in the General Clinical Research Center at Vanderbilt University Medical Center.

Bolander is participating in a clinical trial of a potential new treatment for PWS, a drug called livoletide. The Phase 2b/3 study, called ZEPHYR, is testing whether this novel treatment reduces the insatiable hunger (hyperphagia) that characterizes PWS. Excessive eating that leads to obesity is a major cause of illness and death in people with PWS.

Currently, the only way to manage hyperphagia and overeating is for parents or other caregivers to have strict control over access to food. For parents, it can become exhausting, said Terry Bolander, Joe’s mother.

If treatment with livoletide works to improve hyperphagia, it offers hope for increased independence and improved quality of life for people with PWS and their families.

“I want this drug to be successful not just for me, but for all my Prader-Willi friends,” Joe Bolander said.

“We are excited about offering potential new treatment options for PWS,” said Italo Biaggioni, MD, professor of Medicine and Pharmacology and the lead VUMC investigator for the ZEPHYR study. “Our team at VUMC has a long track record of providing education and behavioral support to patients with PWS and their families, and it’s rewarding to be able to offer new medications that may improve quality of life and impact long-term health.”

Biaggioni also holds the David Robertson, MD, Professorship in Autonomic Disorders.

The study team for the clinical trial of a potential new treatment for Prader-Willi syndrome includes, from left, Italo Biaggioni, MD, Morgan Giesecke, MS, Hailee Hunt-Hawkins and Elizabeth Roof, MA.

VUMC is one of approximately 35 sites worldwide that will enroll 150 patients diagnosed with PWS in the study of livoletide, which is being developed by Millendo Therapeutics, Inc., a biotech company headquartered in Ann Arbor, Michigan. Worldwide, the ZEPHYR study is enrolling patients ages 8 to 65; at VUMC, only adult patients are eligible. Children with PWS are eligible for a trial at VUMC testing a different medication for hyperphagia and anxiety.

The VUMC ZEPHYR study team includes Hailee Hunt-Hawkins, BS, study coordinator, Morgane Giesecke, MS, family nurse practitioner, and Elizabeth Roof, MA, research associate in the Department of Psychology.

Roof has been working with PWS patients for 25 years and currently follows 350 individuals with the disorder. She and Elisabeth Dykens, PhD, professor of Psychology and Human Development, have developed and validated outcome measures to evaluate hyperphagia and food-related behaviors. Their “Hyperphagia Questionnaire for Clinical Trials” is being used in the ZEPHYR study and multiple other trials.

“It is a real privilege to work with these patients and their families, and to help them problem-solve and navigate the challenges of PWS,” Roof said. “It’s gratifying to be in a place now where we are beginning to see treatment options that go beyond support and education.”

PWS affects one in 15,000 people. Although it is considered a rare disorder, it is the most common genetic cause of life-threatening obesity in children. PWS is caused by a spontaneous genetic error that affects genes on chromosome 15 and impairs the brain’s hypothalamus, which normally registers feelings of hunger and satiety.

“People with PWS never feel the sense of contentedness that goes with a full stomach,” Roof said. “Some patients say they are so tired from constantly thinking about and worrying about food.”

“Although we work on managing food-related behaviors, this is really not a behavior problem, it’s a basic biological drive,” added Hunt-Hawkins.

Livoletide is similar to a naturally occurring hormone that counters the actions of the appetite-stimulating hormone ghrelin. The ZEPHYR study is designed to answer the following questions:

  • What are the effects of livoletide on hyperphagia and food-related behaviors in people with PWS?
  • What are the effects of livoletide on body weight, body mass index and fat mass How safe and well-tolerated is livoletide?

In clinical studies to date, livoletide was well-tolerated in healthy volunteers and in patients with PWS, obesity and Type 2 diabetes.

Millendo Therapeutics is funding the ZEPHYR study. More information about the trial is available on clinicaltrials.gov (NCT03790865) or at the patients and families page at Millendo.com. For information or questions about enrollment at VUMC, contact Hailee Hunt-Hawkins at 615-343-0915 or hailee.m.hunt@vanderbilt.edu.