Research & Development
Millendo Therapeutics Releases Topline Results for Pivotal Phase 2b Study of Livoletide in Patients with Prader-Willi Syndrome
7 April 2020 - - US-based biopharmaceutical company Millendo Therapeutics, Inc. (NASDAQ: MLND) is discontinuing the development of livoletide as a potential treatment for Prader-Willi syndrome, the company said.

The decision to discontinue the PWS program was based on topline data from the pivotal Phase 2b ZEPHYR study which showed that treatment with livoletide did not result in a statistically significant improvement in hyperphagia and food-related behaviours as measured by the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) compared to placebo.

The ZEPHYR study was a two-part, randomised, double-blind, placebo-controlled pivotal Phase 2b/3 study. The pivotal Phase 2b study included a three-month double-blind, placebo-controlled period in which patients (N=158) were randomised to either 60 µg/kg or 120 µg/kg of livoletide, or placebo.

The Phase 2b data showed improvements from baseline in HQ-CT scores of -4.7 (p = 0.13) and -3.8 (p = 0.45) for the livoletide treated groups (60 µg/kg or 120 µg/kg, respectively) at 12 weeks compared to -2.8 for placebo.

The average HQ-CT baseline score was 20.2. No positive trends were observed for any of the secondary endpoints of fat mass, body weight or waist circumference.

Livoletide was well tolerated during the ZEPHYR study, with injection site reaction being the most frequently reported adverse event, as expected with an injectable drug, and mostly mild in severity.

A total of 2 patients dropped out of the study during the 12-week core period. There were 4 serious adverse events reported during the 12-week period, with none being related to livoletide treatment.

Millendo has made the decision to stop all livoletide development efforts in PWS, including the 9-month extension study and initiation of the Phase 3 ZEPHYR study.

Livoletide is an unacylated ghrelin analogue in late-stage clinical development for the treatment of hyperphagia in Prader-Willi syndrome.

This rare genetic disease is characterized by hyperphagia, a chronic unrelenting hunger, that leads to obesity, metabolic dysfunction, reduced quality of life and early mortality.

In a randomised, double-blind, placebo-controlled pivotal Phase 2b clinical trial in 158 patients with PWS, administration of livoletide once daily for 12 weeks showed that livoletide did not result in a statistically significant improvement in hyperphagia and food-related behaviors.

Nevanimibe decreases adrenal steroidogenesis through the inhibition of acyl coenzyme A: cholesterol acyltransferase 1, or ACAT1, and is being studied for the treatment of classic congenital adrenal hyperplasia.

CAH is a rare, monogenic adrenal disease that requires lifelong treatment with exogenous cortisol, often at high doses.

These chronic high doses of cortisol can result in side effects that include diabetes, obesity, hypertension and psychological problems. Millendo has received Orphan Drug Designation for nevanimibe for the treatment of CAH from the US Food and Drug Administration and the European Medicines Agency.

In a Phase 2a clinical trial in patients with CAH, Millendo observed nevanimibe to be associated with clear signs of clinical activity in seven of 10 treated patients. A Phase 2b trial of nevanimibe in CAH (NCT03669549) is ongoing.

MLE-301 is a neurokinin 3 receptor antagonist that is being developed as a potential treatment of VMS, commonly known as hot flashes and night sweats, in menopausal women.

NK3R plays a key role in regulating the activity of KNDy (kisspeptin/NKB/dynorphin) neurons, which are believed to participate in the generation of VMS.

By inhibiting the NK3R signaling on the KNDy neurons and potentially other NK3R-expressing neurons that propagate heat dissipation signals through the hypothalamus, MLE-301 aims to reduce the effects of hyperactive KNDy neurons and thereby address the excessive heat dissipation signaling associated with VMS.

MLE-301 is currently in preclinical studies designed to enable first-in-human clinical studies.

Millendo Therapeutics is a biopharmaceutical company primarily focused on developing novel treatments for endocrine diseases where current therapies do not exist or are insufficient.

Millendo seeks to create distinct and transformative treatments where there is a significant unmet medical need.

The company is currently advancing nevanimibe for the treatment of classic congenital adrenal hyperplasia and MLE-301 for the treatment of vasomotor symptoms associated with menopause.
Login
Username:

Password: