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In this special report series from NeurologyLive, leading sleep medicine experts Eric Olson, MD, and Anita Shelgikar, MD—president-elect of the American Academy of Sleep Medicine—offer their perspectives on six late-breaking presentations from the 2025 SLEEP Annual Meeting in Seattle, Washington. With a focus on narcolepsy and hypersomnia, the panel provides timely insights into new and emerging data that could influence future clinical care.

Throughout the series, the discussion covers a range of pressing topics, from cardiovascular safety and high-dose efficacy of low-sodium oxybate to investigational therapies like TAK-861 and ALKS 2680. The panel also unpacks trends in prescribing behavior and the influence of social determinants of health, offering a comprehensive look at the evolving treatment landscape for central disorders of hypersomnolence.

This second episode focuses on early data from the DUET cohort exploring low-sodium oxybate doses above the approved 9-gram ceiling in narcolepsy care. Drs. Olson and Shelgikar discuss reported symptom improvements, tolerability signals, and the potential for individualized dosing in complex cases. They also reflect on the importance of comorbidity management, especially sleep apnea, and consider the need for longer-term data to confirm these initial findings.

Transcript edited for clarity.

Eric Olson, MD: The second abstract to discuss is titled “Effectiveness and Safety of Low-Sodium Oxybate Dosages Greater Than 9 Grams in Study Participants With Narcolepsy.” It’s an interesting concept, because some patients still appear to need additional medication despite maxing out the currently approved sodium oxybate dose.

This study looked at a subset of individuals taking low-sodium oxybate at doses between 9 and 12 grams—9 grams being the current recommended maximum nightly dose. This came from what’s called the DUET cohort, which included 24 participants. The study evaluated the impact on sleepiness, narcolepsy symptom severity, suicide severity scores, treatment-emergent side effects from increasing doses, and importantly, any changes in sleep-related respiratory assessments.

In this group, the mean dose was 11 grams, and patients showed further improvements in symptoms—including lower Epworth Sleepiness Scale scores and reduced narcolepsy symptom severity. Treatment-emergent side effects such as headache, vomiting, and enuresis were reported but at low levels. AHI scores showed minimal change, with a delta of fewer than five events per hour. There were no reports of suicidal ideation or behaviors. So the takeaway is that in this small group, increasing low-sodium oxybate doses above 9 grams appeared to offer further benefit without a major safety concern.

Anita Shelgikar, MD: Thanks for that summary, Eric. I thought this was very interesting because when we manage patients using oxybate, safety is top of mind—especially around dosing, titration, and long-term monitoring. So the idea that we might safely manage symptoms and improve daytime alertness with doses higher than currently approved is really intriguing. I was curious to see that. I did catch that this was an interim analysis, so I’ll be interested to see how things look with the final data.

Eric Olson, MD: Yeah, a couple of questions came up for me. First, I believe the study period analyzed was pretty short—around two weeks—so it makes me wonder how these results would hold up over a longer timeframe. Another point is the effect on sleep-disordered breathing. About a third of participants had comorbid sleep apnea, but we don’t know whether they were being treated. If they were, that could have influenced the AHI data, which didn’t show much change.

A future abstract we’re going to cover looks at concurrent use of alerting agents in patients on oxybates. Clearly, oxybates alone aren’t always enough. So it’s interesting to see that further subjective improvement might be possible by pushing the dose, without a dramatic increase in side effects.

Anita Shelgikar, MD: Absolutely agree. And I think this really speaks to the importance of customizing and individualizing care. You mentioned patients with comorbid obstructive sleep apnea—when does that need to be reassessed? Does treatment for that comorbid sleep disorder need to be revisited to ensure it’s fully effective? I fully agree there are shades of gray and nuance as we manage these patients.

REFERENCE
1. Simmons JH, Schneider LD, Ruoff CM, et al. Effectiveness and Safety of Low-Sodium Oxybate Dosages Greater Than 9 Grams in Study Participants With Narcolepsy. Presented at: 2025 SLEEP Annual Meeting; June 8-11. Seattle, Washington. ABSTRACT LBA 1648

Despite clear clinical guidelines recommending biomarker testing to guide targeted therapies in advanced cancers, a recent cohort study reveals suboptimal testing rates, though these are increasing over time. Importantly, comprehensive genomic profiling (CGP) did not result in higher overall health care costs during first-line therapy compared to non-CGP testing, while showing an increased likelihood of patients receiving appropriate targeted treatments.¹

These findings, published in JAMA Network Open, underscore the critical need to improve access to biomarker testing to optimize patient outcomes.

The retrospective study, leveraging claims data from 26,311 adults with newly diagnosed advanced breast, colorectal, gastric, non–small cell lung, ovarian, and pancreatic cancers, highlights a persistent gap between guideline recommendations and clinical practice. While 35% of patients had evidence of molecular testing before first-line therapy, this figure varied significantly by cancer type, ranging from a low of 17% in ovarian cancer to a high of 45% in non–small cell lung cancer (NSCLC). Although testing rates showed an upward trend from 32% in 2018 to 39% in 2021 to 2022, the overall proportion remains below guideline recommendations.

CGP Boosts Targeted Therapy Uptake

One of the study’s key findings is the association between CGP testing and increased receipt of targeted therapy. Patients with NSCLC and colorectal cancer (CRC) who underwent CGP testing were significantly more likely to receive targeted therapy during first-line treatment compared with those who received non-CGP testing or no testing. For NSCLC, the odds of receiving targeted therapy were 1.57 times higher for CGP-tested patients compared to those with non-CGP testing (P <.001). Similarly for CRC, CGP-tested patients had 2.34 times higher odds of receiving targeted therapy compared to the non-CGP group (P <.001). This suggests that comprehensive profiling offers a tangible benefit in identifying actionable mutations, thereby enabling more patients to access precision medicine.

Cost Neutrality and Clinical Implications

A crucial aspect addressed by the study is the economic impact of CGP. Analysis of per-patient per-month (PPPM) costs during first-line therapy revealed no statistically significant difference in all-cause health care costs between patients who received CGP testing and those who received non-CGP testing across all evaluated cancer types. For instance, the cost ratio for breast cancer was 1.03 (P =.63), for CRC 0.98 (P =.71), and for NSCLC 1.06 (P =.054). While both CGP and non-CGP groups generally had higher costs than the no-testing group, this is likely attributed to the downstream costs of targeted therapies, which are often more expensive but also more effective.

The cost neutrality of CGP is a vital consideration for health care systems and payers. Concerns about the expense of advanced genomic testing have sometimes been cited as barriers to wider adoption. This study provides real-world evidence that the initial investment in comprehensive profiling does not translate into a significant increase in overall first-line therapy costs, especially when considering the potential for improved clinical outcomes through optimized treatment selection.

Addressing the Testing Gap

The study underscores a persistent practice gap between clinical guidelines and the actual implementation of biomarker testing. Despite the growing number of FDA-approved biomarker-targeted therapies and their inclusion in standard treatment guidelines, a substantial proportion of patients with advanced cancer are not receiving recommended testing. This is particularly concerning given the well-established survival advantages associated with biomarker-matched targeted therapies.

“A large body of research has demonstrated the value of biomarker testing, especially for NSCLC,” study authors wrote. “Biomarker testing, when completed before first-line therapy, can meaningfully improve outcomes of patients with NSCLC.^1,2 National clinical guidelines recommend completing broad molecular profiling during the diagnostic evaluation and before initiation of first-line treatment. Despite this evidence, only 45% of patients with NSCLC had evidence of biomarker testing by the start of first-line therapy.”

One factor often cited as a barrier to CGP is inadequate insurance coverage. However, the study found that testing rates in Medicare Advantage beneficiaries were generally lower or comparable to commercial health plan patients, despite comprehensive genomic profiling being covered.¹ This suggests that factors beyond insurance coverage, such as lack of physician awareness, logistical challenges in ordering and processing tests, or delays in obtaining results, may also contribute to suboptimal testing rates.

Future Directions

The study acknowledges limitations inherent in using administrative claims data, such as the inability to capture specific biomarker test results or differentiate between squamous and nonsquamous NSCLC. However, the large cohort size and real-world setting provide valuable insights into current biomarker testing practices and their associated costs and targeted therapy uptake.

Moving forward, interventions are urgently needed to improve biomarker testing rates across all cancer types, especially as more targeted therapies emerge. Healthcare providers should prioritize early and comprehensive genomic profiling for patients with advanced cancers, in line with clinical guidelines. Education initiatives for clinicians, streamlined testing workflows, and improved access to molecular pathology services could all contribute to closing the testing gap. Given the potential for CGP to optimize tissue stewardship, detect genomic signatures like tumor mutational burden, and enhance eligibility for clinical trials, its increased adoption holds significant promise for improving patient outcomes without imposing a substantial additional financial burden.

REFERENCES:

1. DaCosta Byfield S, Bapat B, Becker J, et al. Association of Comprehensive Genomic Profiling and Non–Comprehensive Genomic Profiling With Targeted Therapy Use and Costs in Patients With Advanced Cancer. JAMA Netw Open. 2025;8(7):e2519963. doi:10.1001/jamanetworkopen.2025.19963.

2. Aggarwal C, Marmarelis ME, Hwang WT, et al. Association between availability of molecular genotyping results and overall survival in patients with advanced nonsquamous non-small-cell lung cancer. JCO Precis Oncol. 2023;7:e2300191. doi:10.1200/PO.23.00191