The results of a Phase 2 clinical trial evaluating carbetocin in PWS have just been published in the journal JCI Insight. The findings of the paper, "Intranasal Carbetocin Reduces Hyperphagia In Individuals With Prader-Willi Syndrome," support the advancement of the drug to a larger and longer Phase 3 evaluation in the PWS population.
Carbetocin is a drug that is similar to the hormone oxytocin, which is decreased in the brains of individuals with PWS. Oxytocin influences many aspects of emotion and appetite that are altered in PWS, and the use of intranasal oxytocin to treat PWS is an area of active investigation. Like oxytocin, carbetocin engages the oxytocin receptor, but it binds more tightly to the receptor than oxytocin, and it doesn’t engage the related vasopressin receptor. Since activation of vasopressin receptors can contribute to aggressive behavior, it’s possible that carbetocin would not elicit negative behaviors that were seen when higher doses of oxytocin were tested in older individuals with PWS, per this 2014 study by Einfeld, et al.
This Phase 2 clinical study of intranasal (i.n.) carbetocin was a 15-day randomized, placebo-controlled study of 37 patients, ages 10 to 18 years, with PWS. In the study, 17 patients received drug, and 20 received placebo. Neither the patient nor clinical staff knew who was receiving drug or placebo. Doses of drug/placebo were given 3 times a day for 14 consecutive days, prior to meals, and patients receiving drug were given a total of 9.6mg of carbetocin per dose.
Compared to placebo, the 14-day regimen of i.n. carbetocin significantly reduced hyperphagia and food-related behaviors (hyperphagia is the relentless hunger that is characteristic of PWS). Individuals with PWS often exhibit obsessive-compulsive behaviors, and the i.n. carbetocin also significantly decreased compulsivity compared to placebo, while improving overall functioning. Importantly, treatment with i.n. carbetocin demonstrated a favorable safety profile, with no safety issues identified during the study.
In summary, this randomized, placebo-controlled trial of i.n. carbetocin demonstrated significant improvement in hyperphagia and related behavioral in children with PWS. However, the drug was given only for a limited time (2 weeks). Larger trials with longer treatment duration are needed to further assess the efficacy of i.n. carbetocin on hyperphagia, compulsivity, and social and emotional functioning, as well as to determine if carbetocin can improve weight control in individuals with PWS. In that regard, Levo Therapeutics, a new pharmaceutical company focused on developing new treatments for PWS, acquired the rights to continue the development of carbetocin for the treatment of PWS. Levo is planning a Phase 3 study i.n. carbetocin (LV-101), which is expected to open later this year. The study will require approximately 100 patients between the ages of 7 and 18 with a confirmed diagnosis of PWS. Study sites have yet to be announced but are expected to span across the U.S.