Data from an ongoing Phase 2a clinical trial showed that Tesomet (tesofensine/metoprolol) is safe and well-tolerated by adolescents with Prader-Willi syndrome (PWS).
Eight of the nine adolescents included in the trial have enrolled in an open-label extension (OE) study, where they will proceed with Tesomet treatment for an additional three months.
Despite these positive safety results, the tested dose of 0.125 mg per day of Tesomet failed to achieve the plasma levels that were previously seen to be efficacious in clinical trials in adults.
Given so, Saniona, the developer of the therapy, has asked regulatory agencies for permission to increase the dose up to 0.25 mg per day in the OE trial. The company received approval for this protocol change in the Czech Republic, but is still waiting for a response on how to proceed in Hungary.
Saniona expects patients to start treatment with the 0.25 mg increased dose in March.
“We know from the first part of this Phase 2a study that Tesomet is efficacious in adult patients at a dose of 0.5 mg per day,” Jørgen Drejer, PhD, CEO and founder of Saniona, said in a press release.
“We are now continuing to seek to establish the optimal dosing regimen in the adolescent population. Because of their age, we started with a conservative, low dose of 0.125 mg per day — four times lower than the dose tested in adults, which has not resulted in Tesomet plasma levels correlated with efficacy, and will now double the dose to 0.25 mg/day in the open-label extension,” Drejer said.
Tesomet is a fixed-dose combination of tesofensine and metoprolol. Previous Phase 2 and Phase 3 studies in obese patients showed that the combination is well-tolerated and highly effective in controlling appetite and reducing weight. Tesomet has also been shown to have the potential to reverse the progression of type 2 diabetes by reducing liver fat.
The ongoing Phase 2a study (NCT03149445) in patients with PWS was designed to evaluate the impact of Tesomet on body weight and eating behaviors (including food craving, or hyperphagia) over 12 weeks of treatment, compared to placebo.
In the first part, the study recruited nine adult PWS patients. Although the number of patients was small, researchers were able to observe a clinically meaningful weight loss with daily Tesomet treatment. Change in body weight was 6.01% less and the decrease in average waist circumference was 3.5 cm in the Tesomet group, compared to the placebo group.
A reduction in hyperphagia (abnormally increased appetite) was also reported. After only one week of treatment with Tesomet, the total hyperphagia score fell from 10 at baseline to 5.67, a reduction of 43%.
In the second part of the Phase 2a trial, researchers evaluated the impact of Tesomet in adolescents with PWS.
Following the same trend seen in the adult patient population, Tesomet showed to be very stable and to have a very long half-life in this younger population. However, during the 90-day treatment period, researchers saw some reductions in hyperphagia score, but also an increase in body weight in both Tesomet and placebo groups.
“Based on the strong efficacy on both hyperphagia and weight seen in the first part of the study in adult PWS patients, and the successful Phase 3 trial of tesofensine (the active ingredient in Tesomet) in adult obese subjects, we are confident that a higher dose of Tesomet holds the potential of treating debilitating hyperphagia and significantly reduce weight in this severely underserved population,” Drejer said.
Using the 0.25 mb dose of Tesomet, researchers expect to achieve similar plasma levels of the therapeutic agent in adolescents with PWS to control appetite and reduce body weight.