This drug could be a significant development for patients suffering from the burdensome symptoms of narcolepsy, as well as for doctors who manage their patients with this chronic, incapacitating sleep disorder.
A new form of a narcolepsy drug that patients take once at bedtime rather than twice in the middle of the night eased symptoms in a safe and effective manner.
ON-SXB, the medicine understudy, is an extended-release form of sodium oxybate that must be taken twice a night. The Food and Drug Administration has approved sodium oxybate for the treatment of multiple narcolepsy symptoms, including excessive daytime drowsiness and cataplexy — sudden muscle weakness while awake.
ON-SXB was found to be more effective than a placebo at reducing cataplexy attacks and daytime sleepiness, while also improving clinicians’ ratings of study participants’ overall health.
It had a favorable safety profile, with adverse effects similar to those induced by the twice-daily form of sodium oxybate. By removing the need for a second dose at night, ON-SXB may help patients stick to their medication routine, minimise the risk of falls that result in injury, and enhance nocturnal sleep and overall quality of life.
“Sodium oxybate has largely become a first-line treatment for patients with narcolepsy,” said Clete Kushida, MD, PhD, a professor of psychiatry and behavioral sciences.
“Clinicians can be confident that a single bedtime dose of sodium oxybate has demonstrated efficacy for both objective and subjective symptoms of narcolepsy.”
Narcolepsy is a chronic neurological condition affecting around 135,000 to 200,000 people in the United States. Along with extreme daytime sleepiness and cataplexy, symptoms include disturbed nighttime sleep, sleep paralysis, and hallucinations during sleep or wakefulness. All patients have extreme daytime sleepiness, which manifests as brief sleep bouts that might occur while conversing, eating, or driving.
Cataplexy, another typical symptom, is frequently provoked by strong emotions and occasionally results in falls. This constellation of characteristics can impair psychological and cognitive function and development; it can also significantly impair daily living activities such as school attendance, job, and social interactions.
Sodium oxybate is an effective treatment for a number of narcolepsy symptoms, including interrupted sleep at night. However, due to the medication’s half-life of about 30 minutes to an hour, a second dose is required between 2 and 4 hours following the initial dose. Waking up in the middle of the night to take the prescription can be quite bothersome, particularly when patients already suffer from fragmented sleep and poor sleep quality.
In Europe, a research found that 27 percent of patients suffering from narcolepsy did not take sodium oxybate according to the recommended timetable. When patients are required to take drugs more than once daily, they frequently forget to take them: Other illnesses such as depression, schizophrenia, epilepsy, Type 2 diabetes, cardiovascular disease, chronic obstructive pulmonary disease, and HIV have all been associated with this issue.
“A medication that is taken twice daily — in the morning and evening — is more challenging than a once-daily medication, but it’s even more problematic for a chronic medication requiring middle-of-the-night awakening,” Kushida said.
“Although the labeling advises patients to remain in bed to take the second dose, falls leading to injury and, in some cases, hospitalization have been reported when patients rise from bed.”
From November 2016 to March 2020, the experiment was conducted at 71 sites in the United States, Australia, Canada, and Europe. 222 patients with narcolepsy aged 16 or older were randomly assigned to receive ON-SXB in varied doses or a placebo.
In comparison to placebo, patients receiving the three highest doses of ON-SXB reported considerably reduced daytime sleepiness, fewer weekly cataplexy bouts, less self-reported sleepiness in everyday settings, and higher overall condition scores from their doctors. For instance, 72 percent of people receiving the maximum dose of ON-SXB were deemed to be significantly or very significantly better, compared to 31.6 percent in the placebo group.
ON-SXB has identical side effects to the twice-daily sodium oxybate formulation, including nausea, headache, vomiting, dizziness, involuntary urination, and decreased appetite. However, ON-SXB had a decreased rate of headaches, nausea, and dizziness.
ON-SXB is currently being evaluated by the Food and Drug Administration (FDA) for the treatment of excessive daytime drowsiness and cataplexy in adults with narcolepsy. The FDA designated it as an orphan medication because it may be clinically superior to the twice-nightly sodium oxybate formulation previously licenced for the same ailment. Orphan status is granted to pharmaceuticals used to treat, diagnose, or prevent uncommon diseases that affect fewer than 200,000 individuals in the United States or are unlikely to recoup development and marketing expenditures. Pharmaceutical corporations profit financially from the development of orphan medications.
“If approved, ON-SXB may be a major advance for patients experiencing the burdensome symptoms of narcolepsy and for physicians who manage their patients with this chronic, incapacitating sleep disorder,” Kushida said.
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