New Data on FT218 for Narcolepsy Suggest Clinical Benefit, Once-Nightly Dosing Preference

John Winkelman, MD, PhD

Additional data from the completed phase 3 REST-ON clinical trial (NCT02720744) of FT218, a once-nightly sodium oxybate formulation for treatment of excessive daytime sleepiness (EDS) and cataplexy in patients with narcolepsy, were presented at the 2021 American College of Chest Physicians (CHEST) virtual meeting, October 17-20, 2021. 

Post-hoc data included analyses of sleep latency response and cataplexy response with once-nightly use of the investigational formulation from Avadel Pharmaceuticals. Additional data was presented from a discrete choice experiment (DCE), which evaluated treatment preferences among patients.

Treatment with FT218, also known as ON-SXB, was associated with statistically significant improvements in mean sleep latency, when compared to placebo, according to results from the Maintenance of Wakefulness Test and EDS measures. Participants in the REST-ON trial who received FT218 represented a significantly larger proportion of those who saw an increased mean sleep latency change from baseline (≥5 to 30 minutes). Additionally, data showed improvement for patients receiving the 6-g dose at week 3, increasing with the 7.5-g dose at week 8, and the 9-g dose at week 13. 

Significant improvement in the number of weekly cataplexy episodes was also associated with FT218 treatment, compared to placebo. Patients treated with the 6-g FT218 dose had a 25% reduction in weekly episodes, those treated with the 7.5-g had a 50% reduction, and those treated with the 9-g dose had a 75% reduction. Approximately 10% of patients receiving the 7.5-g and 9-g doses—the 2 highest doses—had elimination of cataplexy, half had a 50% reduction, and one-third had a 75% reduction in weekly episodes.

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“The new post-hoc responder analyses demonstrating that ON-SXB improved EDS provide further confidence in ON-SXB for people with narcolepsy. We believe this is critical for a patient population whose quality of life is severely impacted by EDS,” presenting author, John Winkelman, MD, PhD, professor of psychiatry, Harvard Medical School; and chief, Sleep Disorders Clinical Research Program, Department of Psychiatry, Massachusetts General Hospital, said in a statement.¹ “These ON-SXB data represent a compelling way to set expectations for patients receiving therapy. I believe that ON-SXB, a once-nightly treatment option that has demonstrated clinical benefit in a randomized controlled trial, is a meaningful advance in treatment and, if approved, will be a welcome option for patients and physicians alike.”

Enuresis (9.1%), dizziness (5.2%), and vomiting (5.2%) were the most common adverse reactions to FT218, affecting 5% of more of patients. Drivers of patient preference were evaluated via a DCE, with results suggesting that once-nightly dosing was significantly more preferred than twice-nightly dosing (P <.001), and dosing frequency was noted as the most important attribute of product choice for those with narcolepsy. 

Presentations at CHEST 2021 follow the FDA’s announcement last week that the new drug application for FT218 is still under review.² The NDA was originally accepted by the FDA in February 2021, setting a Prescription Drug Use Fee Act action date of October 15, 2021. Application was based on positive data from the phase 3 REST-ON trial, which was held under a special protocol assessment agreement with the FDA.³

“Avadel is focused on transforming medicines to transform lives, and FT218, if approved, has the potential to be an innovative solution for patients living with the chronic condition of narcolepsy,” Jennifer Gudeman, PharmD, vice president, medical and clinical affairs, Avadel, said in a statement.¹ “FT218 has demonstrated meaningful improvement in cataplexy attacks and measurements of EDS with a dosing regimen preferred by patients. We believe in listening to patients to deliver solutions that improve their symptoms and look forward to our ongoing partnership with the narcolepsy community as we strive to make FT218 available to patients and prescribers.”

REFERENCE

1. Avadel presents new data supporting clinical benefit with once-at-bedtime FT218 and preference for once-nightly dosing in patients with narcolepsy at CHEST 2021. News release. Avadel Pharmaceticals. October 19, 2021. Accessed October 19, 2021. https://www.biospace.com/article/releases/avadel-presents-new-data-supporting-clinical-benefit-with-once-at-bedtime-ft218-and-preference-for-once-nightly-dosing-in-patients-with-narcolepsy-at-chest-2021/?s=69
2. Avadel Pharmaceuticals announces ongoing FDA review of NDA for FT218 for patients with narcolepsy. News release. Avadel Pharmaceuticals. October 15, 2021. Accessed October 19, 2021. https://www.globenewswire.com/news-release/2021/10/15/2315210/0/en/Avadel-Pharmaceuticals-Announces-Ongoing-FDA-Review-of-NDA-for-FT218-for-Patients-with-Narcolepsy.html
3. Kushida CA, Shapiro CM, Roth T, et al. Once-nightly sodium oxybate (FT218) demonstrated improvements of symptoms in a phase 3 randomized clinical trial in patients with narcolepsy. SLEEP. Published online August 6, 2021. doi:10.1093/sleep/zsab200