Lower-sodium oxybate for hypersomnia

In participants with idiopathic hypersomnia, lower-sodium oxybate (LXB) led to a clinically meaningful decrease in excessive daytime sleepiness, self-reported global change, and overall idiopathic hypersomnia symptom severity. The overall safety profile was consistent with that of sodium oxybate (SXB).

LXB contains calcium, magnesium, potassium, and sodium oxybate, representing a novel oxybate treatment with 92% less sodium than SXB. It was tested in patients with idiopathic hypersomnia, a condition for which currently no approved treatment exists [1]. All participants started with 16 weeks of treatment with LXB, during which period the dose was titrated, optimised and, during the last 2 weeks, stabilised. They were then randomised to placebo or to continue LXB for a 2-week withdrawal period. The primary efficacy endpoint was change in Epworth Sleepiness Scale (ESS) score. The safety population included 154 participants, who had a mean ESS of 16; mean dose was 6.0 g/night.

At the end of the double-blind withdrawal period, ESS scores were significantly worse in the placebo group compared with the LXB group, with a mean difference in change of -6.51 (95% CI -7.99 to -5.03; P<0.0001). Patient Global Impression of Change (PGIc) was also significantly worse (21.4% for LXB vs 88.1% for placebo; P<0.0001), as was Idiopathic Hypersomnia Severity Scale (IHSS) score, with an estimated median difference of -12.00 (95% CI -15.0 to -8.0; P<0.0001). Overall incidence of treatment-emergent adverse events was 80%. Treatment-emergent adverse events which occurred in at least 5% of participants were nausea (21.4%), headache (16.2%), dizziness (11.7%), anxiety (10.4%), and vomiting (10.4%). Serious treatment-emergent adverse events occurred in 4 participants, but none were deemed related to study drug.

Results of LXB in patients with narcolepsy with cataplexy were also presented [2]. All participants received LXB during a 12-week optimised treatment and titration period, followed by a 2-week stable-dose period. They were then randomised to placebo or continued LXB treatment during a 2-week withdrawal period. Health-related quality of life worsened in those randomised to placebo but remained stable in participants who continued LXB treatment. The overall safety profile of LXB was similar to SXB.

1. Dauvilliers Y, et al. Efficacy and Safety of Lower-Sodium Oxybate in a Phase 3, Placebo-Controlled, Double-Blind, Randomized Withdrawal Study in Adult Participants With Idiopathic Hypersomnia. AAN 2021 Virtual Congress, 17-22 April.
2. Foldvary-Schaefer N, et al. Quality of Life in a Phase 3, Placebo-Controlled, Double-Blind, Randomized Withdrawal Study of Lower-Sodium Oxybate in Adults With Narcolepsy With Cataplexy. S9.002, AAN 2021 Virtual Congress, 17-22 April.

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Posted on 16 June, 202116 June, 2021