Gaining a Better Understanding of Idiopathic Hypersomnia, Uses of Low-Sodium Oxybate

Marisa Whalen, PharmD

Idiopathic hypersomnia (IH) is an often debilitating, 24-hour neurologic sleep disorder that can significantly impact social, educational, and occupational functioning. Although there are overlapping clinical features with narcolepsy, IH is a condition with its own specific diagnostic criteria. Currently, Xywav (Jazz Pharmacueticals), a low-sodium version of calcium, magnesium, potassium, and sodium oxybates, is the only FDA-approved treatment option for IH in adults, although the exact mechanism for why it’s effective in this patient population is unknown.

At the 2023 SLEEP Annual Meeting, held June 3-7, in Indiana, Indianapolis, Jazz Pharmaceuticals presented several posters, including a real-world claims analysis of the clinical burden of IH, and the interventional SEGUE study, an analysis assessing patients with narcolepsy who transition from high-sodium Xyrem to low-sodium Xywav. The real-world study, otherwise known as RHYTHM, featured 11,428 and 57,138 patients with and without IH, respectively, each of which were matched based on age, sex, region, payer type, and cohort entry date.

To learn more about the significance of each of these studies, NeurologyLive® sat down with Marisa Whalen, PharmD, associate director of Medical Affairs at Jazz Pharmaceuticals, at the meeting. Whalen discussed the major findings from RHYTHM, including the various comorbidities observed in patients with IH, and the complexities that come with treating this patient population. In addition, she spoke about the benefits low-sodium Xywav has on patients with narcolepsy, and why it’s encouraging to see no lost efficacy when transitioning away from Xyrem.

NeurologyLive®: What are the major take-home points the clinical community should be aware of from this real-world analysis?

Marisa Whalen, PharmD: The purpose of the RHYTHM study was to evaluate the clinical burden of idiopathic hypersomnia. We used the MarketScan database to look at diagnostic claims to estimate the prevalence of different medical comorbidities in people with idiopathic hypersomnia, and compare that to a non-IH-matched control group. Essentially, what we found is that patients with idiopathic hypersomnia had a range of medical comorbidities at a higher prevalence compared with that non-IH match group. These included comorbidities like sleep disorders, such as sleep apnea, and included mood disorders, as well as headache and migraine. Additionally, people with idiopathic hypersomnia also had a significantly higher prevalence of cardiovascular conditions, particularly things like hypertension, stroke, and major cardiovascular events compared to that non-IH matched control group. What's notable about that finding is that we did previous research in the narcolepsy population and found consistent results. This reinforces that there might be an association between sleep disorders like narcolepsy in idiopathic hypersomnia, and cardiovascular diseases.

Considering these findings, what are some of the complexities with treating idiopathic hypersomnia?

What we've learned from the RHYTHM study is that patients with idiopathic hypersomnia are quite complex. There’s more that goes into managing them than just treating the symptoms of idiopathic hypersomnia. For healthcare providers, when they see a patient with idiopathic hypersomnia, they might present with other medical comorbidities or they might be at risk of developing some of these other medical conditions down the road, like the cardiovascular conditions. It's important to think about treatment choice from a holistic perspective, based on all of the characteristics of the patient and what they might be suffering from. There are medications that are currently used to treat idiopathic hypersomnia that could increase the risk or exacerbate the risk of developing different cardiovascular conditions.

How has the clinical community taken a more holistic treatment approach?

It is well known that reducing sodium intake across the general population could help prevent or reduce the risk of cardiovascular illnesses. You should not only take into consideration the amount of sodium in your daily diet, but also look at your medications and take into consideration the amount of sodium in them as well. Xywav or low sodium oxybate is an option for patients with idiopathic hypersomnia, and it has 92% less sodium than high sodium oxybate. Now, there is this option for patients with idiopathic hypersomnia to help essentially reduce their excess sodium intake chronically.

For the SEGUE study, why was it so encouraging to see patients easily transition?

In the SEGUE study, patients transitioned from high sodium oxybate to low sodium oxybate, and the goal of that study was to essentially give more information to patients and healthcare providers about what that transition experience looks like. What we found was that the majority of patients were able to transition gram per gram, with no changes in their narcolepsy symptoms. Patients with narcolepsy, who are known to be at increased risk for developing cardiovascular diseases, can transition from a high sodium oxybate product to a low sodium oxybate product with minimal change in their symptoms or impact on the management of their symptoms,

Are there certain patients who may be best suited for Xywav vs Xyrem, and vice versa?

Having more options for patients is great, particularly in a rare disease space, but knowing that Xywav is the only low sodium oxybate option, we do believe that it will remain the oxybate of choice throughout 2023. Lowering sodium intake is not only well understood by the medical community, but it resonates with patients and health care providers in the sleep community. In addition to that, the FDA has also recognized Xywav to be clinically superior to other high sodium oxybate because of the reduction in the sodium content, and the impact that sodium reduction has on developing cardiovascular morbidities.

Transcript edited for clarity. Click here for more coverage of SLEEP 2023.