IPWSO 10th International Conference, Havana, Cuba
The original full publication can be found here: https://especialidades.sld.cu/geneticaclinica/files/2019/11/Clinical-and-Scientific-speaker-and-poster-abstracts-IPWSO-2019.pdf
Tesomet - a new treatment opportunity in Prader-Willi Syndrome. Results from Phase 2a exploratory studies in adult and adolescent patients
Dora Torok, Stanislava Kolouskova, Pavlina Walter, Berit Edsberg & Roman V. Dvorak
Department of Pediatrics, Semmelweis University, Budapest, Hungary
Department of Pediatrics, 2. LF UK, Prague, Czech Republic
Saniona A/S, Ballerup, Denmark
Email addresses: torokdora@gmail.com; stanislava.kolouskova@lfmotol.cuni.cz; pavlina.walter@saniona.com; bed@saniona.com; rdv@saniona.com
Introduction: Prader-Willi syndrome (PWS) is a debilitating, multi-faceted genetic disorder with no effective treatment. One of the hallmarks of this syndrome is insatiable appetite and constant drive to seek food. Tesomet, a combination of tesofensine (a noradrenaline, dopamine and serotonin reuptake inhibitor) and metoprolol (a 1-adrenergic blocker) has demonstrated a significant effect on satiety, appetite and food craving in several patient populations and is now also evaluated in PWS patients as a potential therapy for hyperphagia and overweight in this syndrome.
Methods and results: The Phase 2a exploratory study was conducted at two centers and in two parts: Part 1, a 12 week double-blind placebo-controlled study (randomized 2:1 with 0.5/50 mg of tesofensine/metoprolol in active arm), in nine adult patients; results were reported in 2018 and showed strong reduction in hyperphagia score (HQ-CT scale). Active arm: Reduction in hyperphagia score from 10 at baseline to a mean score of 0 at 12 weeks (mean score of 1 at 8 weeks). The mean weight loss was 6.75% in the active and 0.75% in the placebo arm. Four patients completed the study; noteworthy adverse events were exacerbation of pre-existing behavioral and psychiatric issues. No SAEs were reported. Part 2 of the study enrolled adolescent patients aged 12-18 and was a double-blind, randomized (2:1), placebo-controlled (0.125/25 mg tesofensine/metoprolol and matching placebos), 12-week study, followed by a 12-week open-label extension (OLE1; all patients on Tesomet 0.125/25 mg) and then another 12-week open-label extension (OLE2; patients on Tesomet 0.25/25 mg) if deemed eligible by the investigator and consented to participate. All patients were returning to the sites monthly. Primary endpoint was body weight, secondary endpoints hyperphagia score (HQ-CT), safety (AEs vital signs, ECG, labs), waist circumference, metabolic endpoints and PK. Nine patients were enrolled in the placebo-controlled part; 8 patients agreed to continue into OLE1 and 4 patients into OLE2. The treatment was in general well tolerated; the most frequently reported AEs were headache, insomnia, dizziness, restlessness, palpitations, mood disorders. One non-related SAE was reported. There was no significant effect on the vital signs or laboratory parameters. Part 2 is still ongoing the full data will be presented at the meeting.
Conclusions: Based on data from this Phase 2a exploratory study Tesomet appears to have the potential to provide strong efficacy on hyperphagia and weight with a favorable risk/benefit profile.