In addition to very intense daytime sleepiness, many people with narcolepsy also suffer, among other symptoms, from episodes of cataplexy, the sudden and widespread loss of muscle tone, which greatly affects their quality of life.
Until now, no treatment had managed to address the mechanisms that cause the disease, but two phase III clinical trials published this Wednesday in the journal The New England Journal of Medicine show the positive results of a new therapy that does achieve this goal and significantly improves the symptoms of the disease, such as the ability to stay awake during the day and episodes of cataplexy.
Named oveporexton (Takeda), this drug acts on the key to the disorder, which is associated with the loss of orexin-producing neurons in the hypothalamus. The deficiency in orexin signaling is what causes daytime sleepiness, disruption of nighttime sleep, cataplexy, or sleep paralysis also associated with the disorder.
The new treatment, administered orally, addresses the orexin deficiency by stimulating OX2R, the predominant receptor involved in regulating the sleep-wake cycle.
Last August, the FDA, the agency that regulates drug approval in the US, announced the approval of this treatment for cases of type 1 narcolepsy, the type of narcolepsy that also involves episodes of cataplexy.
The drug's approval was based on the trials whose results are published this Wednesday in the prestigious scientific journal.
Their data show a clear improvement in disease symptoms, such as those related to the ability to stay awake during the day or cataplexy.
These studies independently followed 168 and 105 patients with type 1 narcolepsy. Over 12 weeks, participants received either the treatment or a placebo, during which they underwent various tests to evaluate the progression of the disease.
At the end of the treatment, patients showed a significant improvement in the ability to stay awake during the day. Between 48% and 69% achieved values considered normal in vigilance tests, an achievement that was hardly reached by any participant in the placebo group.
Daytime sleepiness also decreased significantly, with up to 84% of treated patients reaching levels of sleepiness considered normal.
Furthermore, the treatment also significantly reduced episodes of cataplexy, with decreases between 79% and 89% in the weekly number of crises.
Among the side effects observed with the drug were an increase in urinary frequency and transient insomnia.
"Until now, we had treatments that helped control some symptoms of narcolepsy, but this therapeutic approach acts on the biological mechanism that causes the disease," stated Alex Iranzo, head of the Sleep Unit at the Hospital Clínic de Barcelona and the Clinical Neurophysiology group at IDIBAPS, who participated in the research.
"The results show simultaneous improvements in different manifestations of the disease, such as daytime sleepiness and cataplexy, and a significant percentage of patients reached values close to normal in some of the scales used to evaluate the response to treatment," he added.