Millendo Therapeutics Announces Phase 2b/3 Trial Assessing Promising PWS Therapy, Livoletide

A potential new treatment for Prader-Willi syndrome (PWS) will be tested in the large, international clinical trial ZEPHYR, in a partnership between Millendo Therapeutics and several research centers, including The University of Alabama at Birmingham (UAB) and Children’s of Alabama.

ZEPHYR (NCT03790865) is a two-part, randomized, double-blind, placebo-controlled Phase 2b/3 trial that will evaluate the effectiveness and safety of the investigational therapy Livoletide to control chronic overeating (hyperphagia), and other food-related behaviors associated with PWS.

Livoletide (AZP-531) is an analog of unacylated ghrelin (UAG). UAG is one of two forms of the hormone ghrelin; the other is acylated ghrelin (AG). AG is the “hunger hormone” that is secreted in the stomach when empty. It stimulates fat deposition, and induces insulin resistance. In contrast, UAG inhibits AG-induced hunger when the stomach is full, reduces fat deposition, and improves insulin resistance. 

Elevated AG levels compared to UAG are found in PWS patients, and are associated with hyperphagia. Livoletide acts as a substitute for UAG to counteract the hunger induced by AG. 

The study, conducted in two parts, will enroll up to 150 PWS patients, between the ages of eight and 65. Participants will receive Livoletide as a daily under-the-skin (subcutaneous) injection.

The first part is a Phase 2B dose-response study to compare high and low doses of Livoletide (120 and 60 mcg/kg) against a placebo over a three-month period (core period), followed by a nine-month period (extension period) in which placebo subjects from the core period will be switched to high and low doses of Livoletide.

The second part is a Phase 3 study that will begin following a review of the safety and efficacy results at the end of the Phase 2b core period. It will consist of a six-month placebo-controlled core period, followed by a six-month extension period. 

Researchers will assess the effects of Livoletide in a variety of food-related behaviors and PWS outcomes, including hyperphagia (insatiable hunger), body weight, body mass index, and body fat mass.

They also will determine the safety and tolerance of regular Livoletide treatments.

“We are excited that UAB and Children’s of Alabama are a part of a trial that will determine whether we have a viable treatment option for patients living with Prader-Willi syndrome,” Hussein Abdul-Latif, MD, a pediatric endocrinologist at UAB and Children’s of Alabama, said in a UAB press release written by Savannah Koplon.

“We are committed to continuing our research in this rare endocrine disease area together,” Abdul-Latif added.

The ZEPHYR study, which is recruiting volunteers at most of its 31 locations in the U.S. and Europe, is sponsored by Millendo Therapeutics, a clinical-stage biopharmaceutical company focused on developing novel treatments for a wide range of endocrine diseases, including Livoletide for PWS.