Lower-Sodium Oxybate Has Similar Efficacy, Easily Transitions From Higher-Sodium Oxybate

Nancy Foldvary-Schaefer, DO, MS

Data from a recent study suggest that lower-sodium oxybate (LXB) has efficacy in line with sodium oxybate (SXB; Xyrem; Jazz Pharmaceuticals) for the treatment of cataplexy and excessive daytime sleepiness (EDS) in adults with narcolepsy.¹

These findings were presented at the 2021 American Academy of Neurology (AAN) Annual Meeting, April 17-22, by Nancy Foldvary Schaefer, DO, MS, director, Sleep Disorders Center, Cleveland Clinic. Schaefer and colleagues sought to evaluate the initiation and titration of LXB in participants naïve to the treatment as well as dose adjustments and titration in participants previously treated with SXB.

High sodium containing drugs are associated with an increased risk of cardiovascular disease, and at its recommended dosage range of 6-9 g in adults, SXB accounts for 1100-1640 mg of overall daily sodium intake, Schaefer outlined during her presentation. She also discussed her work on a previous phase 3 study that showed cataplexy significantly worsened in adults with narcolepsy after switching to placebo (P <.0001).²

Schaefer and colleagues presented a placebo-controlled, double-blind, randomized withdrawal study that involved a 12-week, open-label optimized treatment and titration period in which LXB was individually titrated and optimized, followed by a 2-week stable dose period and 2-week randomized withdrawal period.

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They enrolled 201 participants as part of the safety population and 134 continued on to form the efficacy population. The safety population consisted of 52 participants who had only taken SXB at entry, 23 who had taken SXB and other anticataplectics, 36 who had taken only other anticataplectics, and 90 who were anticataplectic-naïve.

The researchers found that 91% of those taking SXB at study entry had no dose adjustment or adjustments within 1 titration step (±1.5 g/night). The median number of adjustments was 0.0 (range, 0-8) in participants taking SXB at study entry and 3.0 (range, 0-7) in participants not taking SXB at study entry.

They found that total nightly stable LXB dose was 7.5 g (range, 4.5-9.0; n = 41) in participants taking only SXB at entry and 9.0 g (range, 6.0-9.0; n = 14) in those taking SXB and other anticataplectics compared to 7.5 g (range, 4.5-9.0; n = 21) in those taking other cataplectics without SXB and 7.0 g (range, 3.0-9.0; n = 58) in those who were anticataplectic-naïve. In addition, both time to reach a stable dose and number of dose adjustments were lowest in those who entered the study taking SXB.

The most common treatment-emergent adverse events (TEAEs) were headache, nausea, and dizziness. Participants only taking SXB at entry had the lowest proportion of participants that experienced at least 1 TEAE while participants that had taken other anticataplectics with or without SXB had the highest rates of participants experiencing at least 1 TEAE as well as cases of worsening cataplexy.

“This study demonstrated a treatment effect of LXB similar to that observed with SXB...the overall adverse event profile was consistent with that previously observed for SXB,” Schaefer concluded her presentation.

REFERENCES

1. Foldvary-Schaefer NR, Bogan RK, Thorpy MJ, Huang L, Skowronski R, Dauvilliers Y. Lower-sodium oxybate dose titration and transition from sodium oxybate in a placebo-controlled, double-blind, randomized withdrawal study in adult participants with narcolepsy with cataplexy. Presented at 2021 American Academy of Neurology Annual Meeting; April 17-22. Abstract P26 013
2. Bogan RK, Thorpy MJ, Dauvilliers Y, et al. Efficacy and safety of calcium, magnesium, potassium, and sodium oxybates (lower-sodium oxybate [LXB]; JZP-258) in a placebo-controlled, double-blind, randomized withdrawal study in adults with narcolepsy with cataplexy. Sleep 2021:44(3):zsaa206 doi: 10.1093/sleep/zsaa206