Millendo May Restructure After Prader-Willi Drug Fails Pivotal Test

Xconomy Detroit/Ann Arbor — 

Millendo Therapeutics is considering a corporate reorganization after its lead drug, an investigational treatment for a rare genetic condition characterized by unrelenting hunger, did not perform better than a placebo in a pivotal trial.

The Ann Arbor, MI-based company said Monday that the drug, livoletide, did not meet the goal of the Phase 2b study evaluating it as a treatment for Prader-Willi syndrome. People with this condition—the most common genetic cause of life-threatening childhood obesity—have an insatiable appetite that leads to chronic overeating, or hyperphagia.

Millendo (NASDAQ: MLND) reported that livoletide, compared to a placebo, did not show a statistically significant improvement in hyperphagia or other food-related behaviors according to a questionnaire designed to measure those symptoms. The company’s stock price dropped 70 percent Monday to $1.45 from $4.85 per share as of market close Friday.

A total of 158 patients age 8 to 65 enrolled in the three-month trial. They were randomized to receive either a high or a low dose of livoletide or a placebo injected once daily. Data showed patients in all groups improved compared to the overall group’s average baseline score of 20.2 on the questionnaire. The high and low dose groups improved by by 3.8 and 4.7, respectively, while those who received the placebo improved by 2.8.

The most common side effects were reactions at the injection site. Two patients dropped out of the study during the three-month evaluation; four serious side events reported during the trial were unrelated to the treatment, according to Millendo. CEO Julia Owens said the company intends to share more data from the trial at a future medical meeting or in a publication.

Given the trial failure, Millendo management is evaluating a “revised corporate strategic plan that may include a restructuring,” according to a securities filing. The plan would devote company resources to the company’s two remaining pipeline assets and, possibly, new additions. Millendo’s focus is on novel treatments for endocrine diseases with no or insufficient therapy options.

Millendo has one experimental drug in the the clinic: nevanimibe, which is in Phase 2 testing as a potential treatment for congenital adrenal hyperplasia (CAH). Today patients with the most common form of the disease, classic CAH, have too little of an enzyme that the body needs to make the hormones cortisol and aldosterone. Standard treatment, chronic high doses of cortisol, leads to a range of side effects.

In the last quarter of 2019 Millendo said it anticipated data from a cohort enrolled in the nevanimibe trial in the second half of 2020. That could change, though, given the many clinical trials delays caused by the COVID-19 pandemic, Schwartz added. Hospitals, many of which are sites of clinical trials, are prioritizing their resources to care for COVID-19 patients. Quarantine and shelter-in-place orders are limiting patient movement and interrupting healthcare services. And some healthcare providers have heightened exposure to COVID-19, limiting their ability to participate in clinical trials.

Millendo is also advancing MLE-301, a preclinical compound being evaluated as a treatment for vasomotor symptoms, a term for the hot flashes and night sweats commonly associated with menopause.

Those two drugs work differently than livoletide, so that compound’s failure shouldn’t reflect poorly on their chances as potential treatments, SVB Leerink analyst Joseph Schwartz wrote in a research note.

At the end of 2019, Millendo said it had $63.5 million in cash, money it said would carry it into 2022.

Image: iStock/Oleg Morgun