CARE-PWS: Intranasal oxytocin analogue reduces hyperphagia in Prader-Willi syndrome
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Adults with Prader-Willi syndrome who received an intranasal oxytocin analogue for 8 weeks reported a significant reduction in hyperphagia and symptoms of anxiety and distress, according to topline results of the CARE-PWS study.
CARE-PWS was designed to evaluate two doses of intranasal carbetocin (LV-101, Levo Therapeutics), a selective oxytocin-receptor agonist for the treatment of Prader-Willi syndrome, compared with placebo, specifying a 9.6 mg dose as the primary endpoint and a 3.2 mg dose as the first secondary endpoint. In a press release, Levo Therapeutics stated that the phase 3 study achieved statistical significance with the secondary endpoint evaluating the 3.2 mg dose; however, the study did not meet its primary endpoint evaluating the 9.6 mg dose of LV-101. Enrollment for the study was closed early due to COVID-19, with 119 evaluable patients in the primary analysis set.
“This is a long-awaited step toward addressing the substantial needs of individuals living with Prader-Willi syndrome,” Sara Cotter, CEO of Levo Therapeutics, said in the release. “We are excited by these important results that were achieved after decades of interest in addressing the oxytocin deficiency in Prader-Willi syndrome. We are also pleased that our efforts to develop new tools for clinical evaluation of this rare, neurodevelopmental disorder have enhanced our understanding of the real-world impact LV-101 has on anxiety and distress behaviors.”
Levo stated that statistical significance was achieved with the 3.2 mg dose as evaluated by the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score (P = .016). When pooling the two dose arms of LV-101, per a prespecified analysis, the change in HQ-CT score from baseline to week 8 resulted in a P value of .055. Consistency in benefit/response was observed in the 3.2 mg dose arm across other key secondary endpoints, including clinical global impression of change (P = .027) and anxiety and distress behaviors, as evaluated by the PWS Anxiety and Distress Behaviors Questionnaire (P = .027). Neither dose demonstrated a statistically significant effect on the Children’s Yale-Brown Obsessive Compulsive Scale.
On completion of the 8-week placebo-controlled period, 98% of participants chose to transition into a long-term follow-up period and receive intranasal carbetocin.
“Of note, further improvements in scores were observed and subsequently maintained after week 8 in both dose arms,” the release stated.
Safety data showed that intranasal carbetocin generally was well-tolerated. Compared with placebo, treatment-emergent adverse events occurring in 5% or more of participants receiving the 3.2 mg dose included headache (16.3% vs. 7%), flushing (14% vs. 0), diarrhea (9.3% vs. 2.3%), nasal discomfort (7% vs. 2.3%), pyrexia (7% vs. 0) and upper respiratory tract infection (7% vs. 4.7%), all of which were considered mild or moderate. Incidence of reported adverse events among participants who received the 9.6 mg dose compared with placebo were flushing (20.5% vs. 0), epistaxis (13.6% vs. 2.3%), and headache (9.1% vs. 7%), also considered mild to moderate in severity.
“The results from the CARE-PWS study have brought hope to the Prader-Willi syndrome community as together we pursue effective therapies for these patients in need,” Theresa V. Strong, PhD, founding member of the Foundation for Prader-Willi Research, said in the release. “We look forward to continuing to partner with Levo Therapeutics to help bring LV-101 expeditiously to the Prader-Willi syndrome community.”
In the release, Levo Therapeutics stated that all CARE-PWS participants will be transitioned to the 3.2 mg dose of LV-101 for the remainder of their long-term follow-up and extension periods.
As Healio previously reported, the FDA in November granted fast track designation for intranasal carbetocin for the treatment of Prader-Willi syndrome. The drug is approved in more than 90 countries outside the United States for the prevention of uterine atony and excessive bleeding during cesarean section delivery, with an estimated cumulative exposure of more than 10 million patients.
“We look forward to working closely with regulatory authorities in the United States and abroad to bring this promising therapeutic to patients as quickly as possible,” Cotter said.
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