Tesomet for treatment of Prader-Willi Syndrome and Hypothalamic Obesity

Tesomet is an investigational fixed-dose combination therapy of tesofensine (a triple monoamine reuptake inhibitor) and metoprolol (a beta-1 selective blocker). Saniona is advancing Tesomet for hypothalamic obesity and Prader Willi syndrome, two severe rare disorders characterized by obesity and loss of appetite control. The programs are currently in clinical development. Saniona holds worldwide rights to Tesomet and is actively evaluating opportunities to advance this treatment globally.

PRADER-WILLI SYNDROME

Prader-Willi syndrome (PWS) is a rare disease characterized by constant, extreme, ravenous, insatiable appetite (hyperphagia) which persists no matter how much the patients eat. The urge to eat is physiological, overwhelming, and difficult to control. Caregivers need to strictly limit the patients' access to food, usually by installing locks on refrigerators and cabinets where food is stored. Many of those affected with PWS become morbidly obese and suffer shortened life expectancy and significant mortality. Common causes of mortality in PWS include respiratory disease, cardiac disease, infection, choking, gastric rupture, and pulmonary embolism. However, if obesity is avoided and complications are well managed, life expectancy for individuals with PWS is normal or near normal, and most individuals can lead healthy lives. Currently, there is no cure for this disease. PWS results from a deletion or loss of function of a cluster of genes on chromosome 15, which leads to dysfunctional signaling in the brain’s appetite/satiety center (hypothalamus). PWS occurs in approximately one out of every 15,000 births.

On September 18, 2019, Saniona reported positive top-line results from an exploratory, randomized, double-blind, placebo-controlled Phase 2a proof-of concept study in Prader-Willi syndrome. The first part of this exploratory Phase 2a study in PWS had demonstrated that Tesomet is highly efficacious in adult patients with PWS at a dose of 0.5 mg per day and suggested that patients would also benefit from a lower dose. The  exploratory extension study in an adolescent population shows that Tesomet appears to be safe and well tolerated at lower doses (0.125 mg/day and 0.25 mg/day) and that it provides dose dependent effects on weight, BMI and hyperphagia. 

HYPOTHALAMIC OBESITY

Hypothalamic obesity (HO) is a rare disorder characterized by uncontrollable hunger leading to rapid and intractable weight gain. Additional symptoms may include memory impairment, attention deficit, impulse control and depression as well as increased risk of cardiovascular and metabolic disorders. Currently, there is no cure for this condition. Treatments used for general obesity such as surgery, medication and counseling are often tried in HO, but are mostly ineffective, and there are no medications specifically approved for HO. HO is caused by injury to the hypothalamus, most commonly sustained during surgery to remove a rare, noncancerous tumor called a craniopharyngioma. This tumor can occur at any age, but is most common in children and older adults, creating a burden for both patients and families. HO occurs in approximately one out of every 50,000 to 100,000 people.

On April 22, 2020 Saniona reported positive top-line results from its 24-week double blind, randomized, placebo-controlled Phase 2 trial evaluating the safety and efficacy of Tesomet in patients with hypothalamic obesity (HO). Tesomet was well-tolerated. Patients receiving Tesomet demonstrated statistically significant and clinically meaningful reductions in body weight and waist circumference, as well as improvements in glycemic control. These improvements were maintained during an additional 24-week open-label extension, as reported Nov. 23, 2020. No clinically meaningful differences in heart rate or blood pressure were observed over the course of the trial.