Avadel Pharmaceuticals announced its investigational, once-nightly formulation of sodium oxybate, FT218, met all 3 of its co-primary end points in the phase 3 REST-ON trial (NCT02720744) for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy.
All 3 doses (9 g, 7.5 g, and 6 g) of FT218 demonstrated highly significant, clinically meaningful improvements on the Maintenance of Wakefulness Test (MWT), Clinical Global Impression-Improvement (CGI-I) scores, and mean weekly cataplexy attacks.
Researchers noted that the once-nightly 9-g FT218 demonstrated highly statistically significant (P <.001), and clinically meaningful improvement across all 3 co-primary endpoints compared to placebo. The same dose was generally well-tolerated with commonly known sodium oxybate adverse reactions occurring at low rates.
The change from baseline to Week 13 in patients who used once-nightly 9-g FT218 on MWT was 10.82 minutes, compared with 4.69 minutes for placebo (P <.001). CGI-I, measured as the percentage of patients who were “much” or “very much” improved from baseline was 72% and 31.6% for 9-g FT218 and placebo, respectively (P <.001). Additionally, the same dose showed a reduction of 11.51 mean weekly cataplexy attacks, compared with just 4.86 for placebo (P <.001).
“Once-nightly FT218 delivered a clinically meaningful response within 3 weeks of treatment initiation, which was sustained through each treatment period,” Jordan Dubow, MD, chief medical officer, Avadel, said in a statement. “Commonly known sodium oxybate adverse reactions occurred at low rates at the highest dose level.”
According to the clinicaltrials.gov site, REST-ON was a phase 3, double-blind, randomized, placebo-controlled, multicenter study that assessed the efficacy and safety of for the treatment of excessive daytime sleepiness and cataplexy in subjects with narcolepsy. The study contained 218 patients and used longer MWT sleep latency, improvement in CGI-I sleepiness scores, and reduction of cataplexy attacks all as primary end points. An additional secondary end point was fewer polysomnography transitions from N1, N2, N3 and rapid eye movement (REM) sleep to wake and from N2, N3, and REM sleep to N1.
The 9 g dose of FT218 demonstrated the agent’s generally safe profile, with commonly known adverse events (AEs) such as nausea, vomiting, decreased appetite, dizziness, somnolence, tremor, and enuresis occurring 1.3%, 5.2%, 2.6%, 3.9%, 1.3%, and 9% of patients on treatment, respectively. Discontinuation occurred in 3.9% of patients on the 9 g dose.
FT218 was previously granted an orphan drug designation by the FDA for the treatment of narcolepsy on the basis that it may be clinically superior to the twice-nightly formulation of sodium oxybate, an already FDA-approved medication for the same indication.
“We look forward to sharing the results from the REST-ON study with the FDA and progressing toward a potential approval that would allow us to bring this important treatment to the patients who need it most. If approved, FT218 would be the first once-nightly therapy to address both excessive daytime sleepiness and cataplexy in patients with narcolepsy,” Greg Divis, chief executive officer, Avadel, said in a statement.
Avadel Pharmaceuticals announces positive topline results from its pivotal phase 3 REST-ON trial of once-nightly FT218 for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy [news release]. Dublin, Ireland: Avadel Pharmaceuticals. Published April 27, 2020. Accessed May 12, 2020. globenewswire.com/news-release/2020/04/27/2022300/0/en/Avadel-Pharmaceuticals-Announces-Positive-Topline-Results-from-its-Pivotal-Phase-3-REST-ON-Trial-of-Once-Nightly-FT218-for-the-Treatment-of-Excessive-Daytime-Sleepiness-and-Cataple.html