Phase 2b/3 Trial of Livoletide Completes Enrollment of PWS Patients Ages 8 to 65

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by Steve Bryson, PhD |

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A Phase 2b/3 clinical trial of livoletide, a treatment candidate for excessive eating in people with Prader-Willi syndrome (PWS), has completed recruitment of participants who are 8 to 65 years old.

However, enrollment of patients from 4 to 7 years old is still ongoing. More information on contacts and locations is available here.

Millendo Therapeutics’ livoletide (AZP-531) is an analog of unacylated ghrelin (UAG), one of two forms of the hormone ghrelin — the other is acylated ghrelin (AG).

When the stomach is empty, AG, also known as the “hunger hormone,” is secreted to stimulate eating. It also induces fat deposition and insulin resistance. UAG blocks AG-induced hunger when the stomach is full, decreasing fat deposition and insulin resistance. People with PWS have higher levels of AG than UAG.

Livoletide acts as a replacement for UAG to prevent hunger. Its therapeutic potential was supported by the results of a Phase 2 trial, which revealed that daily injections of livoletide for 14 days produced a meaningful decrease in hyperphagia and appetite in 47 adolescents and adults with PWS. 

ZEPHYR (NCT03790865) is an international two-part study investigating the safety and effectiveness of livoletide. Its Phase 2b part will compare the effects of low and high doses of livoletide (60 and 120 mcg/kg) to those of a placebo. A three-month period (core period) will be followed by a nine-month extension, in which participants previously on placebo will be switched to one of the two doses of the experimental therapy. 

So far, all participants who have completed the Phase 2b core period have entered the nine-month extension.

Overall, this first part will include more than 150 patients selected from 38 clinical sites in the United States, Europe, and Australia. 

“Completing recruitment of over 150 patients in this pivotal study is an important step forward as we continue our efforts to advance livoletide,” Julia C. Owens, president and CEO at Millendo, said in a press release.

The Phase 3 part will begin after full evaluation of safety and efficacy data from Phase 2b. It will involve a six-month placebo-controlled core period, followed by a six-month extension period. 

Researchers will assess the change in food-related behaviors using the validated Hyperphagia Questionnaire for Clinical Trials, a caregiver-reported assessment that focuses on food-seeking behaviors. Safety and tolerance of regular livoletide treatment will also be assessed.

According to the company, top-line results are expected in the first half of 2020 and may help support a New Drug Application for livoletide.

“We are very pleased with how quickly our participating trial sites were able to recruit for ZEPHYR,” said Ryan Zeidan, PhD, the company’s chief development officer. “Throughout this process, we have seen enthusiasm from our active sites and we appreciate their partnership as we work toward our common goal of addressing hyperphagia in PWS.”  

“We are grateful to the patients, families and caregivers and investigators involved in the study for their commitment and dedication,” he said.