A recent study titled “Effect of FT218, a Once-Nightly Sodium Oxybate Formulation, on Disrupted Nighttime Sleep in Patients With Narcolepsy: Results From the Randomized Phase 3 REST-ON Trial,” was published in CNS Drugs. Its purpose was to investigate how FT218 treated disrupted nighttime sleep (DNS) in adult narcolepsy patients. REST-ON and FT218 differ from other clinical development programs dedicated to narcolepsy in that they focus on a nighttime symptom of the rare disease. Most drugs target daytime symptoms – which is very important, but leaves an unmet need for effects like DNS.

Back in 2020, initial data was published on this Phase 3 trial that demonstrated FT218’s primary efficacy and safety. Later in the year, additional data was presented at events like SLEEP and World Sleep. It was these data that led to the submission of a marketing application to the FDA. Now, Avadel Pharmaceuticals has released positive secondary endpoint data through the paper published in CNS Drugs.

About the New Data

While initial data focused on the three co-primary endpoints of the study, this recent publication surrounds the various secondary endpoints of the REST-ON trial. These include nocturnal arousals, patient-reported sleep quality, visual analog scale, polysomnographic measures of sleep stage shifts, and patient reports on how refreshing their sleep is. Here are some highlights of the data:

• Significant decrease in the number of transitions in:
  • Stages N1, N2, N3, and rapid eye movement (REM) sleep to wake
  • Stages N2, N3, and REM sleep to stage N1
  • Note: These observations were seen across doses of 6, 7.5, and 9 g
• Significant decrease in the number of nighttime disturbances when compared to the placebo group
  • Note: These observations were seen across doses of 6, 7.5, and 9 g
• Patient-reported sleep quality and refreshing nature of sleep also saw significant improvements when compared to the placebo group
  • Note: These observations were seen across doses of 6, 7.5, and 9 g
• Post-hoc data showed:
  • Improvements in sleep architecture
  • Improvements in DNS
    • This benefit was seen despite use of concomitant stimulants

About FT218

This investigational formula of sodium oxybate utilizes Avadel’s proprietary technology to treat adults with narcolepsy. It was designed to take once every day before bed. It received the FDA’s Orphan Drug designation back in 2018 and is now awaiting on a decision on a marketing application. In addition, it is still being studied in the ongoing, open-label RESTORE trial, which focuses on long-term safety and tolerability.

About Narcolepsy

Narcolepsy is a neurological disorder that stops the brain from regulating one’s sleep-wake cycle. It is characterized by instantly falling asleep for a few minutes or longer, depending on the severity of one’s symptoms. Some people experience hallucinations while asleep or directly after waking up. People also often have cataplexy, which is the sudden loss of muscle control, along with narcolepsy, but this is not the case for everybody. When people have both disorders it is known as type one narcolepsy. Cataplexy is triggered by a strong emotion, such as fear or anger, and it manifests as uncontrollable muscle weakness or paralysis. Those who have cataplexy without narcolepsy are often misdiagnosed, as doctors think it is a seizure disorder. Depending on severity, cataplexy can be slight eyelid drooping or the inability to remain standing. One is usually awake during a cataplectic attack but are unable to move. As cataplexy is often related to narcolepsy, people fall asleep after an attack.

The most common cause of an attack is laughter. The destruction of the neurotransmitter hypocretin, which regulates wakefulness, is the root of cataplexy. The cause of narcolepsy type two, which is narcolepsy without cataplexy, is unknown. It is believed that genetics play a part in the disorder, but it is not often passed down from parent to child. Symptoms of type two narcolepsy include sleep paralysis, hallucinations, and changes in rapid eye movement (REM) sleep. In terms of treatment, there are drugs available to treat cataplexy. Xyrem, which was approved in 2002 by the FDA, is used to treat narcolepsy itself, but due to its high potential for abuse it is tightly regulated. Besides drugs, people with narcolepsy often take regularly scheduled naps and do not drink alcohol or caffeine before bed.

Find the source article here.