Michael Thorpy, MD, director of the Sleep-Wake Disorders Center at Montefiore Medical Center and professor of neurology at Albert Einstein College of Medicine, discusses the findings and implications of his study on the efficacy of JZP-258 in patients with narcolepsy and cataplexy.
Many patients who are already receiving sodium oxybate are choosing to switch to the low sodium formulation, JZP-258, said Michael Thorpy, MD, director of the Sleep-Wake Disorders Center at Montefiore Medical Center and professor of neurology at Albert Einstein College of Medicine.
What did you find in your study on the safety and efficacy of JZP-258 in patients with narcolepsy and cataplexy?
JZP-258 is a new formulation of oxybate that doesn't contain a high sodium load. In fact, this form of oxybate has 92% less sodium. There have been concerns with regard to the traditional form of oxybate, which has a high sodium content, and that it may worsen underlying cardiovascular disorders. Patients who have renal disorders or congestive heart failure can be bothered by the excess sodium load. This new formulation has the advantage that it doesn't have so much sodium, so it may be beneficial not only to those patients who have comorbidities that could be worsened by it, but also there's increasing evidence for the development of cardiovascular disorders in patients with narcolepsy, particularly high blood pressure. So, patients who are otherwise healthy, there may be a protective effect in the long-term of reducing sodium intake.
This study was a study that was a withdrawal study, where patients were all titrated on JZP-258, the low sodium formulation of oxybate. And they were adjusted and stabilized on it, and then the medication was withdrawn and patients were assessed to see what happens in terms of their sleepiness and their cataplexy. The study showed that when they were taken off the low sodium formulation that these symptoms returned. So the study confirmed the fact that oxybate is an effective treatment for excessive daytime sleepiness and cataplexy and that this new formulation, which has a lower sodium content, could be as equally as effective as the traditional form, which has a larger sodium content.
What are the clinical implications of these findings in regard to tapering or discontinuing use of other anticataplectics?
This new formulation of oxybate has a lower sodium content, so it has some advantages over the traditional sodium oxybate. Not only in patients who have comorbidities that may be worsened by a high sodium content, but for patients going forward who don't have any cardiovascular disorders but may in the future develop them. Because there is evidence that patients with narcolepsy have a higher potential for developing high blood pressure. So, having a low sodium formulation is preferable, and what we're finding is that new patients who are starting on oxybate, we generally start them with this new low-sodium formulation rather than the older sodium form.
For patients who are already on the sodium oxybate, many of those patients are choosing to change over to this new low-sodium formulation because they can see the benefits of reduced sodium sodium intake. This is often encouraged by the clinician to get them away from a high sodium load on to a much lower sodium intake. So there [are] patients changed over; it's a very simple process, because the same amount of the active moiety of oxybate is contained in both these formulations, so somebody who may be, for example, on 9 g of sodium oxybate can immediately change over to 9 g of the new formulation with the low sodium.
It's an easy process. There are many patients who have had difficulty handling the sodium oxybate because the salt content has caused them to have adverse effects, such as nausea and gastric discomfort. Now they're choosing to go back to oxybate and try the new low-sodium formulation in the hope that this will help to mitigate some of the side effects that they've had in the past.
Some patients who initially were treated with oxybate but found that they couldn't take it, we're treating some of those patients now with this new formulation. So it has a big advantage to patients with narcolepsy.