The Food and Drug Administration (FDA) has approved Xywav™ (calcium, magnesium, potassium, and sodium oxybates; Jazz Pharmaceuticals) oral solution for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients aged ≥7 years with narcolepsy.

Xywav is a novel oxybate product believed to exert its therapeutic effects through GABAB during sleep. It contains the same oxybate concentration as Xyrem (sodium oxybate; Jazz Pharmaceuticals), but with a unique composition of cations resulting in 92% less sodium (approximately 1000 to 1500mg/night).

The approval was based on data from 2 multicenter, double-blind, placebo-controlled, randomized-withdrawal phase 3 studies that evaluated the efficacy and safety of Xywav in the treatment of cataplexy and EDS in adults (Study 1) and pediatric patients (Study 2) with narcolepsy. Both studies included a titration and stable-dose period, followed by a double-blind randomized-withdrawal period in which patients were randomized 1:1 to receive either Xywav or placebo for 2 weeks. The primary end point for both studies was the change in the number of cataplexy attacks; a key secondary end point included the change in Epworth Sleepiness Scale (ESS) score.

Results from Study 1 showed that patients in the placebo arm had a significant increase in the median weekly number of cataplexy attacks (2.4 vs 0.00, respectively; treatment difference, P <.0001) and median ESS score (2.0 vs 0.0, respectively; treatment difference, P <.0001) compared with Xywav.

In Study 2, pediatric patients randomized to placebo experienced a statistically significant increase in weekly cataplexy attacks (median change from baseline: 12.7 vs 0.3, respectively; P <.0001) and median ESS score (median change from baseline: 3.0 vs 0.0, respectively; P =.0004) compared with those treated with Xywav.  Additionally, the placebo arm experienced a statistically significant worsening of cataplexy severity and narcolepsy overall according to clinician’s assessment.

With regard to safety, the most common adverse reactions observed with Xywav in adults included headache, nausea, dizziness, decreased appetite, parasomnia, diarrhea, hyperhidrosis, anxiety, and vomiting. The most common adverse reactions in pediatric patients included enuresis, nausea, headache, vomiting, weight decreased, decreased appetite, and dizziness.

Xywav, a Schedule III controlled substance, carries a Boxed Warning regarding central nervous system depression; clinically significant respiratory depression and obtundation has occurred in adult patients taking sodium oxybate at recommended doses in clinical trials. Due to its potential for abuse and misuse, Xywav is only available through a restricted distribution program.

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“Xywav makes it possible for patients to have a lower-sodium oxybate treatment option,” said Richard K. Bogan, MD, FCCP, FAASM, associate clinical professor at the University of South Carolina School of Medicine, a medical officer at SleepMed in Columbia, SC and lead investigator of the phase 3 study. “This may help patients taking sodium oxybate better align with daily sodium intake recommendations including those by the American Heart Association.”

Xywav is expected to be available at the end of 2020 following Risk Evaluation and Mitigation Strategy (REMS) implementation. The product will be supplied as 0.5g/mL total salts (equivalent to 0.413g/mL of oxybate) in 180mL bottles.

For more information visit jazzpharma.com.