Once-nightly narcolepsy drug formula may benefit sleepyheads

Use of FT218, an investigational, once-nightly, controlled-release formulation of sodium oxybate (SO), led to clinically significant improvements in sleep parameters in individuals with narcolepsy, according to the secondary endpoint data from the pivotal phase III REST-ON* trial presented at AAN 2021.

 

“The positive results previously [reported] regarding the coprimary endpoints are further bolstered by the [current findings,]” said study investigator Dr Michael Thorpy from the Montefiore Medical Center, Bronx, New York, US, in a press release.

 

Despite the proven efficacy of a twice-nightly SO formulation for excessive daytime sleepiness (EDS) and cataplexy in patients with narcolepsy, an extended-release (ER) formulation has been developed as a potential once-nightly treatment. [https://www.restontrial.com/patient.html#, accessed May 18, 2021] “[FT218 has the] potential to improve sleep disruption based on its unique ER profile,” noted Thorpy and colleagues.

 

To ascertain the efficacy of the once-nightly regimen, the team randomized 212 participants to receive either FT218 or placebo. The four-period uptitration dosing schedule was as follows: 4.5 g (1 week), 6.0 g (2 weeks), 7.5 g (5 weeks), and 9.0 g (5 weeks). Total study duration was 17 weeks. The doses evaluated were 6.0, 7.5, and 9.0 g at weeks 3, 8, and 13, respectively.

 

In terms of Epworth Sleepiness Scale measurements, improvements were noted in favour of FT218 over placebo, given the significant least-squares mean [LSM] differences between arms across all doses evaluated (–2.06, –3.16, and –3.86 for 6.0, 7.5, and 9.0 g; p<0.001 for all). [AAN 2021, abstract P26.011]

 

Compared with placebo, the same FT218 doses yielded better results in terms of self-reported sleep quality/refreshing nature of sleep on Visual Analogue Scale, as well as for sleep paralysis based on a sleep symptom diary (p=0.039, p=0.021, and p=0.037, respectively).

 

The researchers noted similar results between arms for hypnagogic hallucinations.

 

“[The] significant and clinically meaningful results [with FT218] compared with placebo at the doses tested … represent improvement on important narcolepsy symptoms,” said the researchers.

 

The most common adverse events (AEs) associated with FT218 use were nausea, headache, dizziness, enuresis, reduced appetite, and vomiting. “[These] reactions were well-known and established SO AEs … FT218 was generally well-tolerated,” they added.

 

Another analysis looked into the effect of FT218 on polysomnographic (PSG) measures of disturbed nocturnal sleep (DNS), including number of arousals. [AAN 2021, abstract P26.012]

 

“DNS is inherent to narcolepsy, and is characterized by fragmented sleep, including frequent, brief nightly awakenings,” the researchers explained. FT218 outshined placebo in terms of DNS improvements, given the significant LSM differences between study arms across all doses tested (–11.00, –17.70, and –22.63 for 6.0, 7.5, and 9.0 g, respectively; p<0.001 for all).

 

Regarding number of arousals, LSM differences between FT218 and placebo were –11.29 (p<0.021), –19.41 (p<0.001), and –23.68 (p<0.001) for the 6.0-, 7.5-, and 9.0-g doses, respectively.

 

“FT218 demonstrated significant consolidation of sleep vs placebo at all doses tested … [Taken together, the findings suggest that] FT218 could offer a new once-nightly treatment option for disrupted night-time sleep in patients with narcolepsy,” said the researchers.

 

“The consistency with which FT218 improved both subjective and objective symptoms of narcolepsy, including DNS, represent the promise of a potential new treatment strategy for physicians and patients. I am particularly impressed by the consistency of results as early as 3 weeks, with only a 6.0-g dose,” said Thorpy.

 

FT218 is currently under review by the US FDA, with a Prescription Drug User Fee Act target action date of October 15, 2021.