Livoletide (AZP-531) / Jazz, Tempest Therap - LARVOL DELTA

Hyperphagia in Prader-Willi syndrome with obesity: From development to pharmacological treatment. (PubMed, Intractable Rare Dis Res) - "Treatment in the form of drugs such as livoletide, topiramate, and diazoxide could potentially alleviate these abnormalities and make hyperphagia less prominent in PWS. The approaches are important to regulate the hormonal changes and neuronal involvement as potentially controlling hyperphagia and obesity."

Journal • Review • Genetic Disorders • Obesity • Prader–Willi syndrome • LEP

Three-dimensional growth of breast cancer cells potentiates the anti-tumor effects of unacylated ghrelin and AZP-531. (PubMed, Elife) - "The mechanism of unacylated ghrelin-mediated growth inhibition involves activation of Gαi and suppression of MAPK signaling. AZP-531 also suppresses the growth of breast cancer cells in vitro and in xenografts, and may be a novel approach for the safe and effective treatment of breast cancer."

Journal • Breast Cancer • Oncology • Solid Tumor

[VIRTUAL] Juvenile Toxicity Study of Livoletide: A Peptide Analogue of Unacylated Ghrelin for the Treatment of Hyperphagia in Prader-Willi Syndrome (ENDO-I 2020) - "Livoletide was well-tolerated and not associated with evidence of overt systemic toxicity. The no observed adverse effect level (NOAEL) of 75 mg/kg/day was associated with Cmax and AUC0-24h values of 72.6/83.2 μg/mL and 169/144 μg.h/mL (males/females), respectively. These exposures are >100-fold above the anticipated clinical exposures in the Phase 2b/3 ZEPHYR study, which is enrolling people ages 4 to 65 with PWS."

Endocrine Disorders • Prader–Willi syndrome • IGF1

[VIRTUAL] Livoletide (AZP-531), an Unacylated Ghrelin Analogue, Improves Hyperphagia and Food-Related Behaviors Both in Obese and Non-Obese People with Prader-Willi Syndrome (ENDO-I 2020) - "These results highlight the potential of livoletide for treating hyperphagia in both obese and non-obese people with PWS and hyperphagia. Livoletide is being investigated further in the ZEPHYR Phase 2b/3 trial, an ongoing pivotal study on the long-term safety and efficacy of livoletide in the treatment of hyperphagia and food-related behaviors in people with PWS."

Obesity • Prader–Willi syndrome

ZEPHYR: Effects of Livoletide (AZP-531) on Food-related Behaviors in Patients With Prader-Willi Syndrome (clinicaltrials.gov) - P2b; N=158; Terminated; Sponsor: Millendo Therapeutics SAS; Trial completion date: Mar 2021 ➔ May 2020; Active, not recruiting ➔ Terminated; Trial primary completion date: Jun 2020 ➔ Feb 2020; Livoletide did not result in a statistically significant improvement in hyperphagia and food-related behaviors

Clinical • Trial completion date • Trial primary completion date • Trial termination • Prader–Willi syndrome

ZEPHYR: Effects of Livoletide (AZP-531) on Food-related Behaviors in Patients With Prader-Willi Syndrome (clinicaltrials.gov) - P2b; N=158; Active, not recruiting; Sponsor: Millendo Therapeutics SAS; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Genetic Disorders • Prader–Willi syndrome

"$MLND to discontinue livoletide program in PWS and focus on development of pipeline assets nevanimibe and MLE-301" (@BioStocks)

Juvenile Toxicity Study of Livoletide: A Peptide Analogue of Unacylated Ghrelin for the Treatment of Hyperphagia in Prader-Willi Syndrome (ENDO 2020) - "The no observed adverse effect level (NOAEL) of 75 mg/kg/day was associated with C max and AUC 0-24h values of 72.6/83.2 μg/mL and 169/144 μg.h/mL (males/females), respectively. These exposures are >100-fold above the anticipated clinical exposures in the Phase 2b/3 ZEPHYR study, which is enrolling people ages 4 to 65 with PWS."

IGF1

Livoletide (AZP-531), an Unacylated Ghrelin Analogue, Improves Hyperphagia and Food-Related Behaviors Both in Obese and Non-Obese People with Prader-Willi Syndrome (ENDO 2020) - "These results highlight the potential of livoletide for treating hyperphagia in both obese and non-obese people with PWS and hyperphagia. Livoletide is being investigated further in the ZEPHYR Phase 2b/3 trial, an ongoing pivotal study on the long-term safety and efficacy of livoletide in the treatment of hyperphagia and food-related behaviors in people with PWS."

E42. Exploring the Management of Prader-Willi Syndrome: Disease Burden, the Role of Ghrelin in Hyperphagia, and an Investigative Treatment in Development (ENDO 2020) - "Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by hyperphagia and obesity, resulting in high disease burden. Learn about current PWS management strategies, the role of ghrelin, and livoletide, a novel unacylated ghrelin analog being investigated to treat hyperphagia in PWS."

"Millendo Therapeutics Completes Patient Recruitment for Pivotal Study of Livoletide in Prader-Willi Syndrome https://t.co/RlzTF06CuO" (@NewsFromBW)

Clinical

"Millendo Therapeutics Announces 21st European Congress of Endocrinology 2019 Presentations on Livoletide for Prader-Willi Syndrome and Nevanimibe for Classic Congenital Adrenal Hyperplasia https://t.co/9d4YSjEZmv" (@NewsFromBW)

Trial-in-Progress: ZEPHYR, a Pivotal Phase 2b/3 Randomized, Placebo-Controlled Study of Livoletide, a Novel Unacylated Ghrelin Analog, for the Treatment of Hyperphagia and Food-Related Behaviors in Patients with Prader-Willi Syndrome (ENDO 2019) - P2b; "ZEPHYR is a pivotal study that will provide data on the long-term safety and efficacy on hyperphagia and food-related behaviors of the novel UAG analog livoletide in patients with PWS.*Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference."

Clinical • P2/3 data • P2b data

Nonclinical Development of AZP-531 (Livoletide): A Peptide Analog of Unacylated Ghrelin for the Treatment of Hyperphagia in Prader-Willi Syndrome (ENDO 2019) - "Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*"

ZEPHYR: Effects of Livoletide (AZP-531) on Food-related Behaviors in Patients With Prader-Willi Syndrome (clinicaltrials.gov) - P2b; N=150; Recruiting; Sponsor: Millendo Therapeutics SAS; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Trial-in-Progress: ZEPHYR, a Pivotal Phase 2b/3 Randomized, Placebo-Controlled Study of Livoletide, a Novel Unacylated Ghrelin Analog, for the Treatment of Hyperphagia and Food-Related Behaviors in Patients with Prader-Willi Syndrome (ENDO 2019) - "ZEPHYR is a pivotal study that will provide data on the long-term safety and efficacy on hyperphagia and food-related behaviors of the novel UAG analog livoletide in patients with PWS."

Clinical • P2/3 data • P2b data

A Clinical Study in patients with Prader-Willi-Syndrome (PWS) to test if a study drug named livoletide can reduce food related behaviour and be safe and well tolerated. (clinicaltrialsregister.eu) - P2/3; N=150; Sponsor: Millendo Therapeutics SAS

Clinical • New P2/3 trial