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Unassigned

New Medicines

Xywav Narcolepsy with cataplexy and excessive daytime sleepiness in adults

Information

Xywav
New formulation
Jazz Pharmaceuticals
Jazz Pharmaceuticals

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Launched
Jun 21US FDA grant 7 years of Orphan Drug Exclusivity for Xywav for cataplexy or excessive daytime sleepiness (EDS) in people aged 7+ with narcolepsy. [14]
Feb 21In its latest 10Q form, Jazz does not describe any plans to file a licence application in the UK or EU for JZP-258 [9].
Nov 20Launched in the US [11].
Jul 20Approved in the US for treatment of cataplexy or EDS in narcolepsy patients seven years of age and older. The 92% reduction of sodium translates into a reduction of approximately 1,000 to 1,500 milligrams per day for a patient prescribed an oxybate product, depending on the dose. When patients start Xywav after sodium oxybate, Xywav treatment is initiated at the same dose and regimen as sodium oxybate (gram for gram) and titrated as needed based on efficacy and tolerability. The label for Xywav, unlike Xyrem, does not include a warning to prescribers to monitor patients sensitive to sodium intake, including patients with heart failure, hypertension or renal impairment [11].
Apr 20In the latest company annual report, plans for US filing described but no mention of whether a licence application will be filed in the EU [10].
Jan 20Jazz has announced the submission of a NDA to the FDA seeking marketing approval for the treatment of cataplexy and excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy [9].
Nov 19Jazz intends to submit a NDA to the US FDA in Jan 20, and plans to redeem its priority review voucher for this submission [8].
Jan 17First patient enrolled in PIII trial [2].

Category

An oxybate mixed salt solution having sodium oxybate, potassium oxybate, calcium oxybate and magnesium oxybate but with 90% less sodium than sodium oxybate (Xyrem)
Prevalence is estimated as 25 per 100,000 in Caucasian populations [1].
Narcolepsy with cataplexy and excessive daytime sleepiness in adults
Oral

Trial or other data

Sep 19PIII study (N= 201, NCT03030599) met primary and key secondary endpoints demonstrating statistically significant differences in the weekly number of cataplexy attacks and Epworth Sleepiness Scale scores vs. placebo. The trial included pts previously treated with sodium oxybate and naïve to sodium oxybate, with or without other anticataplectic treatments.During the double-blind withdrawal period, the median weekly number of cataplexy attacks were lower for JZP-258 vs. placebo; (median [Q1, Q3]: 2.35 [0.00, 11.61] vs 0.00 [−0.49, 1.75], P<0.0001. The safety profile was consistent with that reported with sodium oxybate. Two pts experienced treatment related side effects; a confused state and visual hallucination after accidental JZP-258 overdose.[7]
Apr 19PIII study NCT03030599 in narcolepsy patients with cataplexy found significant differences in the change in the weekly number of cataplexy attacks and secondary endpoint of change in Epworth Sleepiness Scale (ESS) score with JZP-258 compared to placebo (primary endpoint). In a continuation study, patients were randomized to either continue JZP-258 or placebo. Those randomized to JZP-258 showed clinically meaningful maintenance of efficacy for both cataplexy and EDS, while both cataplexy and ESS worsened in the placebo group [6].
Nov 18PIII trial (NCT03030599) has finished recruiting & expects to complete collection of primary outcome data in Jan 19 [5].
Mar 18PIII trial (NCT03030599) is still recruiting & expects to complete collection of primary outcome data in Oct 18 [4].
Nov 16PIII trial to evaluate the efficacy and safety of JZP 258 oral solution, against excessive daytime sleepiness and cataplexy in adult and elderly patients with narcolepsy due to start (NCT03030599). Primary endpoint is change in weekly number of cataplexy attacks. The double-blind, placebo-controlled, randomised-withdrawal study is enrolling approximately 185 patients in Czech Republic, Spain, France, the UK, Germany, Belgium, Denmark, Finland, Italy, Netherlands, Sweden, Switzerland, and the US [3].

Evidence based evaluations

Xywav Idiopathic hypersomnia

Information

Xywav
Licence extension / variation
Jazz Pharmaceuticals
Jazz Pharmaceuticals

Development and Regulatory status

None
None
Launched
Yes
Aug 21Approved in US where it had Fast Track and Priority review designation. Because of the risks of CNS depression and abuse and misuse, Xywav is available only through a restricted program called the Xywav and Xyrem REMS [10,11]
Apr 21In its latest 10Q form, Jazz does not describe any plans to file a licence application in the UK or EU for JZP-258 [9].
Apr 21US FDA accept sNDA and set PDUFA goal date for a decision as 12/08/2021 [8].
Feb 21Jazz Pharmaceuticals announce submission of sNDA to FDA [7].
Nov 20Jazz has yet to announce if it plans to file for approval of JZP-258 in the EU/UK [5,6].
Sep 20Jazz expects to submit a supplemental new drug application in Q1 2021 with potential approval and launch in the Q4 2021. FDA has granted fast track designation for JZP-258 [5].
Nov 19Has orphan drug status for hypersomnia in the US [3].

Category

An oxybate mixed salt solution having sodium oxybate, potassium oxybate, calcium oxybate and magnesium oxybate but with 90% less sodium than sodium oxybate (Xyrem)
Idiopathic hypersomnia is a sleep disorder classified in two forms: idiopathic hypersomnia with long sleep time and idiopathic hypersomnia without long sleep time. The prevalence is unknown but has been estimated at 1 per 10,000 to 1 per 25,000 for the first form and 1 per 11,000 to 1 per 100,000 for the second one. Both forms start before the age of 25 years old and affect both sexes equally [1].
Idiopathic hypersomnia
Oral

Trial or other data

Oct 20Jazz announces positive top-line results from the PIII trial [5].
Oct 19PIII trial (NCT03533114) is recruiting [4].
Nov 18PIII trial to evaluate safety and efficacy of JZP-258 for treatment of idiopathic hypersomnia starts (JZP080-301; NCT03533114). The primary endpoint of the study is change in Epworth Sleepiness Scale (ESS) score. 140 patients will be recruited in the US. Collection of primary outcome data is due to complete Sep 20 [2].

Evidence based evaluations