New narcolepsy drug targets disease mechanism for first time

The US Food and Drug Administration approved a new narcolepsy medicine, Orzeyful, in early August, ERR reports. Based on the active ingredient oveporexton, the drug marks a breakthrough in sleep medicine but will not help all narcolepsy patients.

Narcolepsy, also known as sleeping sickness, is a debilitating disorder characterised by sudden sleep attacks, muscle weakness known as cataplexy and sleep paralysis. For decades, doctors have treated only its symptoms with stimulants and sedatives rather than addressing the underlying cause, Nature News reports.

Researchers at pharmaceutical company Takeda have now targeted the biological mechanism behind the disease. Orzeyful replaces the neurotransmitter orexin, which is missing in the brain and regulates the sleep wake cycle.

Narcolepsy is divided into type 1 and type 2. Muscle weakness occurs in patients with type 1 narcolepsy, whose orexin producing cells have been destroyed. The resulting deficiency prevents the brain from properly distinguishing between sleep and wakefulness.

Orzeyful acts in the brain like natural orexin by activating the same receptors and restoring interrupted signalling. In clinical trials, patients who received the drug stayed awake significantly longer during the day and experienced substantially fewer cataplexy attacks.

Causes of the disease still require study

Although the drug could offer a promising treatment for type 1 narcolepsy, it is not suitable for everyone. The causes of type 2 narcolepsy remain unclear, and this form does not appear to be directly linked to an orexin deficiency. As a result, patients with type 2 narcolepsy are unlikely to benefit directly from the development.

Jerome Siegel, a sleep psychiatrist at the University of California who was not involved in developing the drug, said that even type 1 narcolepsy is not fully understood. The loss of orexin may not be the only cause of the disease. Siegel’s research also points to the destruction of neurons in other parts of the brain, including the locus coeruleus, or blue spot.

This means that future treatments focused solely on orexin may not be sufficient. Artificially activating the orexin system also presents new challenges. Doctors who conducted the clinical trials said the drug had several side effects. Although patients generally tolerated it well, they more frequently reported difficulty falling asleep, an increased need to urinate and increased saliva production.

Despite these side effects, scientists said the approval represents a major step forward in sleep medicine and could pave the way for a new generation of brain medicines.