Jazz Pharmaceuticals’ narcolepsy drug bested placebo at keeping patients awake during the day and tamping down on cataplexy attacks, or sudden and uncontrollable muscle weakness or paralysis that affects people with narcolepsy during the day.
The phase 3 study, presented at the World Sleep Congress on Wednesday, pitted the drug, a low-sodium follow-up to Jazz’s sleepiness med Xyrem, against placebo in 134 patients. The patients had undergone various treatments for narcolepsy before starting the study, including with Xyrem alone, with Xyrem and another cataplexy-fighting drug, or with another anticataplectic drug alone.
All of the patients went through a 12-week optimization and titration phase, during which they were weaned off their previous treatments and brought up to a stable dose of the experimental drug, JZP- 258. Then, half of the patients carried on with JZP-258 and the other half received placebo for two weeks.
After that two-week period, the patients taking placebo had a “significant increase” in median weekly cataplexy attacks compared to those taking JZP-258, whose rate of cataplexy attacks stayed consistent. Previously treated JZP-258 patients saw a spike in attacks as they stopped taking their old drugs, but these attacks stabilized during the two-week stable-dose period.
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Placebo patients also logged a “significant increase” in median scores on a patient questionnaire to measure excessive daytime sleepiness compared to patients taking JZP-258. The safety profile of the new drug was on par with that seen in clinical trials of Xyrem, with the most common side effects being headache, nausea and dizziness.
“Phase 3 study design makes direct comparison to Xyrem impossible. But importantly, cataplexy remained stable for patients who transitioned from Xyrem to JZP-258 which suggests similar efficacy to Xyrem,” wrote RBC Capital Markets analyst Randall Stenicky in a note. “Moreover, the overall adverse event profile for JZP-258 appears to be largely consistent with Xyrem. As expected, this makes the primary point of differentiation for JZP-258 its 92% less sodium content and the long-term safety benefits that go along with that.”
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Stanicky pointed out that its “unclear” how important the low-sodium nature might be to doctors and patients, but that it could be appealing to “a meaningful portion” of patients, especially those at risk for heart disease.
"It's encouraging to see these positive results from the Phase 3 study, as JZP-258 may represent an important and novel product candidate for people with narcolepsy with the benefit of a 92% reduction in sodium compared to sodium oxybate," said lead investigator Richard Bogan, MD, associate clinical professor at the University of South Carolina School of Medicine and SleepMed chief medical officer, in a statement. "This is important for people living with narcolepsy because narcolepsy is a chronic condition that may require lifelong treatment, and is associated with increased risk of comorbid conditions, including hypertension and cardiovascular disease."
RBC expects Jazz to file JZP-258 for approval before the end of the year and to launch the drug in the second half of 2020 if Jazz uses a priority review voucher to speed the process. If it doesn’t, they expect the new drug to launch in early 2021. Xyrem faces generic competition in 2023.
“We expect focus to now shift to commercial strategy where we think a partial ‘switch’ strategy is likely,” Stanicky wrote.
“Jazz also declined to comment on its commercial strategy. However, we assume that the company prices JZP-258 at a slight premium to Xyrem and targets the higher risk population first. A 'full' switch risks triggering generic acceleration clauses contingent upon a 'substantial reduction' in Xyrem sales,” he wrote.