Levo Therapeutics announced top-line results from the Phase 3 CARE-PWS clinical study evaluating LV-101 (intranasal carbetocin) for the treatment of Prader-Willi Syndrome (PWS). CARE-PWS tested two doses of LV-101 versus placebo. Following the FDA’s discussion, enrollment in the trial was closed early due to COVID-19, with 119 evaluable patients in the Primary Analysis Set. While the primary endpoint was not reached, a key secondary endpoint was achieved.
CARE-PWS was a multi-center, randomized, double-blind, 8-week placebo-controlled study designed to test the effectiveness, safety, and tolerability of LV-101 (intranasal carbetocin) in participants age 7-18 with PWS. Effectiveness was measured using both caregiver-reported and clinician-reported measures of hyperphagia (extreme hunger), obsessive and compulsive behaviors, and anxiety. The trial tested two doses of LV-101 versus placebo with even randomization (1:1:1), specifying the 9.6 mg dose as the primary endpoint and the 3.2 mg dose as the first secondary endpoint.
As stated, the study did not meet its primary outcome measurements, evaluating the 9.6 mg dose of LV-101 (intranasal carbetocin). However, statistical significance was achieved with the 3.2 mg dose as evaluated by the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score as the first secondary endpoint. Consistency in benefit/response was observed in the 3.2 mg dose arm across other key secondary endpoints, including clinical global impression of change and anxiety and distress behaviors, as evaluated by the PWS Anxiety and Distress Behaviors Questionnaire. Neither dose demonstrated a statistically significant effect on the Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). LV-101 was generally well-tolerated in the study.
Treatment-emergent adverse events occurring in 5% or more of participants during the placebo-controlled period at the 3.2 mg dose include headache, flushing, diarrhea, nasal discomfort, pyrexia, and upper respiratory tract infection, all of which were considered mild or moderate.
All patients actively participating in CARE-PWS are being transitioned to receive the 3.2 mg dose of LV-101 for the remainder of their long-term follow-up and extension periods.
About LV-101 (Carbetocin)
Carbetocin is an analog of the naturally occurring neuroendocrine hormone oxytocin. Carbetocin was designed to have an improved receptor binding profile compared to oxytocin, with greater affinity for the oxytocin receptor and lower affinity for related vasopressin receptors. Deficiency in oxytocin is believed to be contributory to the symptoms of Prader-Willi Syndrome.
About Prader-Willi Syndrome (PWS)
PWS is a complex, multisystem neurodevelopmental disorder that occurs in approximately 1 in 16,000 births. The underlying cause of PWS is the lack of expression of paternally-inherited imprinted genes on chromosome 15q11-q13. These genetic anomalies lead to a distinctive phenotype that includes mild to moderate levels of intellectual disability, compulsivity, growth hormone deficiency, life-threatening hyperphagia, and anxiety.