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Top-line phase 3 results announced for Carbetocin trial – positive results at low dose

AUG 2020 – Oxytocin (OT) is a naturally occurring hormone released from the hypothalamus in the brain. It is associated with maternal care, bonding, feeding in infancy, social cognition, OCD, anxiety and appetite control. Carbetocin is an oxytocin-like drug which is thought to positively affect appetite and emotion because of the decreased levels of oxytocin hormone in PWS, thought to contributing to the behavioural alterations in these areas. Carbetocin specifically targets only the oxytocin receptor which may reduce impact on other systems, i.e. vasopressin signalling, and is therefore thought to limit any potential unwanted side effects. (Activation of vasopressin receptors could generate aggression.)

Carbetocin is administered intranasally (via nasal spray). After significant improvements in hyperphagia and compulsive behaviours were observed during a phase 2 trial sponsored by Ferring Pharmaceuticals, the rights to develop Carbetocin were purchased by Levo Therapeutics, a company with a personal connection to PWS and committed to developing new treatments. Carbetocin was renamed LV-101, was granted fast track designation by the FDA and a large scale phase 3 trial was planned.

The CARE-PWS phase 3 trial for LV-101 recruited 7-18 yr olds at various sites across the USA and Canada, with participants administered LV-101 three times daily before meals. Participants were randomised to receive either a 9.6mg dose, a 3.2mg dose or placebo. The study was intended to recruit 175 participants, but reduced to 119 due to the Covid-19 pandemic closing enrollment early. Top-line results for CARE-PWS have been announced and although the study did not meet its primary outcome measurements evaluating the 9.6 mg dose of LV-101, statistically significant reductions in hyperphagia and symptoms of anxiety and distress were observed with the 3.2mg dose, in which carbetocin was generally well-tolerated. However, the low dose did not improve obsessive-compulsive behaviours.

Although the higher dose did not prove effective, more than 98% of CARE-PWS participants elected to receive the lower 3.2mg dose in the long-term follow up extension period following the initial placebo-controlled trial. The extension programme continues to see maintained benefits or improvements in scores.

This research has shown that for some patients with PWS, oxytocin treatments can be beneficial in reducing the symptoms of hyperphagia and anxiety at optimal dose.