Millendo Therapeutics presented an overview of its Phase 2b/3 clinical trial testing the long-term safety and efficacy of livoletide — a potential first-in-class treatment to control hyperphagia (excessive hunger) and food-related behaviors in Prader-Willi syndrome (PWS) — at the 21st European Congress of Endocrinology on May 18–21, 2019, in Lyon, France.
Livoletide (AZP-531) is an analog of unacylated ghrelin. When the stomach is empty, ghrelin, commonly known as the “hunger hormone,” is secreted. When the stomach is stretched, ghrelin secretion stops.
There are two forms of ghrelin with different biological activities: acylated (AG, with a short fatty acid attached), which increases appetite; and unacylated (UAG, without the fatty acid), which inhibits AG-induced food intake. Studies indicate that the ratio of AG to UAG is elevated in PWS patients compared with aged-matched healthy subjects, and is associated with hyperphagia.
Livoletide has received orphan drug designation from the U.S. Food and Drug Administration and the European Medicines Agency for the treatment of PWS.
In a previous Phase 2 clinical trial involving 47 patients with PWS, daily subcutaneous injections of livoletide for 14 days produced a clinically meaningful decrease in hyperphagia, as well as a reduction in appetite.
The new Phase 2b/3 clinical trial, known as ZEPHYR (NCT03790865), began in March 2019 and is expected to recruit 150 participants from up to 40 sites in the U.S. and Europe. Two posters were presented on livoletide at the European Congress of Endocrinology, according to a press release.
The first was a ZEPHYR trial overview, in a poster titled “Trial-in-Progress: ZEPHYR, a Pivotal Phase 2b/3 Randomized, Placebo-Controlled Study of Livoletide, a Novel Unacylated Ghrelin Analogue, for the Treatment of Hyperphagia and Food-Related Behaviors in Patients with Prader-Willi Syndrome.”
The second poster is a description of the non-clinical development of livoletide in animal models — “Nonclinical Development of Livoletide (AZP-531), a Peptide Analogue of Unacylated Ghrelin for the Treatment of Hyperphagia in Prader-Willi Syndrome.” This program was designed to determine the safety pharmacology and the toxicologic profile of livoletide. Results showed that the therapy was very well-tolerated, not cytotoxic, and not associated with adverse effects on major physiological systems.
Top-line results from the Phase 2b portion of ZEPHYR trial are expected in the first half of 2020. The company hopes that the study results will provide evidence for a new drug application (the final step to obtain marketing approval) for the therapy.