Millendo Starts Phase 2b/3 Study Evaluating Livoletide as PWS Treatment

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by Santiago Gisler |

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Millendo Therapeutics has launched a Phase 2b/3 clinical trial investigating the safety and efficacy of livoletide (AZP-531) in patients with Prader-Willi syndrome (PWS), the company announced.

The rare genetic disease is characterized by hyperphagia (excessive eating) and obesity, caused by abnormal hormonal levels. Livoletide is designed to reduce appetite by blocking the activity of ghrelin, a hormone (also known as the “hunger hormone”) produced in the gastrointestinal tract.

“Livoletide is an exciting investigational drug for Prader-Willi syndrome that has the potential to treat hyperphagia, the unrelenting hunger that often leads to excessive eating and is a root cause of morbidity and mortality in PWS patients,” Maithé Tauber, MD, professor of pediatrics at the University of Toulouse and chief of endocrinology and medical genetics at the Children’s Hospital of Toulouse, France, said in a press release. “Current strategies to manage the disease present a heavy burden on caregivers, and do not address the underlying hyperphagia experienced by patients.”

The ZEPHYR study (NCT03790865) is a two-part, placebo-controlled, clinical study aiming to recruit 150 patients from up to 40 sites in the U.S. and Europe.

In the Phase 2b part, patients will receive subcutaneous injections of livoletide (60 or 120 mcg/kg) or placebo for three months. The three-month core period is then followed by an extension period of nine months where all patients receive the active therapy. In the Phase 3 part, patients will receive livoletide or placebo for six months, followed by a six-month extension period.

The primary endpoint will compare food-related behaviors with baseline scores using the Hyperphagia Questionnaire for Clinical Trials. The study will also measure changes in fat percentage, waist size, and body weight.

“Livoletide has the potential to be an important new treatment option that could positively impact the lives of patients and their caregivers,” Tauber said.

Livoletide is an unacetylated form of ghrelin, similar to the more common acetylated form. A previous study showed an elevated ratio between acetylated and unacetylated ghrelin in PWS, and the therapy is believed to restore the balance and hence decrease ghrelin-associated hyperphagia.

”The initiation of our pivotal trial for livoletide is an important step toward our mission to bring life-changing therapies to market for rare endocrine diseases with significant unmet medical needs, like Prader-Willi syndrome,” said Pharis Mohideen, MD, chief medical officer at Millendo. “We are pleased that multiple clinical sites are actively enrolling patients, and we expect to report topline results from the Phase 2b portion of ZEPHYR in the first half of 2020.”

Millendo officials hope that the study results will support a new drug application (the final step to get marketing approval) for the therapy.

The U.S. Food and Drug Administration and the European Medicines Agency have both granted livoletide orphan drug designation for the treatment of PWS.