Universit� degli studi di Modena e Reggio Emilia

Important steps forward to counter type 1 narcolepsy from a study co-coordinated by Unimore

The New England Journal of Medicine published the results of a phase 2 study conducted on individuals with type 1 narcolepsy, co-led by Professor Giuseppe Plazzi – neurologist, coordinator of the Centre for Narcolepsy and Sleep Disorders at the IRCCS Institute of Neurological Sciences of Bologna, and Professor of Child and Adolescent Neuropsychiatry at Unimore.

Type 1 narcolepsy (NT1) is a rare and serious chronic neurological condition caused by the significant loss of orexin-producing neurons. Orexin is a key neuropeptide involved in regulating the sleep–wake cycle and appetite. The resulting low orexin levels lead to excessive daytime sleepiness (EDS), cataplexy (sudden loss of muscle tone), cognitive symptoms, disrupted night-time sleep, hallucinations upon falling asleep or waking up, and sleep paralysis. These debilitating symptoms can significantly reduce quality of life and severely impact work performance, academic achievement, and personal relationships. Current standard treatment consists of polytherapy to manage the various symptoms, but none of the existing medications address the underlying orexin deficiency that causes NT1.

The study, which enrolled 112 adults aged 18 to 70 with NT1 across several countries, specifically investigated the effects of an orexin agonist on daytime sleepiness, wakefulness maintenance during the day, and the frequency of cataplexy episodes.

Orexin agonist Orexoporexin is a selective oral orexin receptor 2 (OX2R) agonist, designed to address the orexin deficiency underlying NT1 and capable of restoring orexin signalling. The results showed significant improvements in both objective and subjective measures of excessive daytime sleepiness, reductions in cataplexy episodes, and clinically meaningful improvements in disease severity and quality of life at all tested dosages compared with placebo over the eight-week treatment period.

“Type 1 narcolepsy is a condition that affects individuals around the clock, making it extremely difficult to lead a healthy and productive life,” stated Professor Giuseppe Plazzi. “For people living with this form of narcolepsy, going to work or school, managing everyday tasks such as driving, exercising, or socialising with family and friends can be immensely challenging. The phase 2b results suggest that restoring orexin signalling may help people with type 1 narcolepsy achieve near-normal levels of wakefulness – similar to those seen in healthy individuals – while also positively influencing the broader spectrum of the disease.”

The data show statistically significant improvements in both primary and secondary endpoints: most participants achieved normal scores in the Maintenance of Wakefulness Test (MWT) and experienced clinically meaningful improvements across a broad range of symptoms studied. Phase 3 results are expected in 2025.

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