Jazz Pharmaceuticals plc (a merger of Jazz Pharmaceuticals, Inc. and Azur Pharma plc) is a biopharmaceutical company based in Ireland. It was founded in 2003. One of the company's most significant products is the United States Food and Drug Administration (FDA) approved drug Xyrem (sodium oxybate), the sodium salt of the naturally occurring neurotransmitter γ-Hydroxybutyric acid (GHB). In 2017, net product sales of Xyrem were $1.187 billion, which represented 74% of the company's total net product sales. In 2019, Jazz was granted FDA-approval to market Sunosi with indications for treating excessive daytime sleepiness (EDS) in narcolepsy as well as obstructive sleep apnea (OSA). In 2007, the company pled guilty to felony charges related to its illegal marketing of Xyrem for off-label use.The company is also a member of the Pharmaceutical Research and Manufacturers of America (PhRMA).
A phase 4, prospective, open-label study of low-sodium oxybate (LXB) in narcolepsy (type 1 [NT1] or 2 [NT2]) or idiopathic hypersomnia included novel symptom outcomes important to patients (Jazz DUET; NCT05875974; registered 16 May 2023). Primary results from the narcolepsy cohort, including LXB effectiveness (nighttime sleep/daytime symptoms/overall disease severity) and safety are reported here. DUET included screening, 8-day baseline (BL; off-LXB), 2–8-week LXB dose titration/optimization, 2-week stable-dose, 8-day end-of-treatment (EOT; on-LXB), and safety follow-up periods. At BL and EOT, participants underwent nocturnal polysomnography (PSG) and completed Epworth Sleepiness Scale (ESS; primary endpoint), Narcolepsy Severity Scale (NSS [NT1]; NSS-2 [NT2]), and Patient Global Impression of Severity (PGI-S) and Change (PGI-C); eDiaries for sleep quality and cataplexy (NT1 only) were completed daily for 8 days before PSGs. Least-squares mean (LSM) changes were adjusted for BL values. Thirty-four participants completed the study and were analyzed (NT1, n = 16; NT2, n = 18); LSM (SE) change in ESS score (BL to EOT), − 7.7 (0.9), P < 0.0001. At EOT versus BL, transitions to lighter stages of sleep decreased (LSM [SE] − 13.1 [2.9], P < 0.0001), N3 duration increased (45.0 [8.8] min, P < 0.0001), and nocturnal awakenings decreased (− 3.2 [0.9], P = 0.0013). LSM [SE] changes in NSS and NSS-2 scores were − 19.7 (2.7) and − 11.3 (1.6). Most participants reported improved sleep quality and overall narcolepsy disease and fewer cataplexy attacks. Treatment-emergent adverse events were consistent with the known LXB safety profile. DUET study results demonstrated novel nighttime sleep/daytime symptom improvements in participants with narcolepsy treated with open-label LXB. ClinicalTrials.gov identifier, NCT05875974. Low-sodium oxybate (LXB; Xywav®), a medication that contains calcium, magnesium, potassium, and sodium oxybates, is approved for treating excessive daytime sleepiness or cataplexy (sudden muscle weakness) in people aged 7 years and older with narcolepsy. LXB is also approved for treating idiopathic hypersomnia in adults. The DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment) study tested sleep and daytime symptoms in people with narcolepsy who took LXB. Before starting LXB, people in the study completed tests to measure their symptoms and sleep patterns. Then they started taking LXB. Study doctors adjusted LXB doses over 2–8 weeks to find the best dosage for each person. After the best dosage was found, people took that dosage for 2 more weeks. At the end of the study, people took the tests again while taking LXB. The study looked at changes in test findings before and after taking the best dosage of LXB. People took LXB for 5–12 weeks. Fifty-five people with narcolepsy started taking LXB. After LXB treatment, people had less daytime sleepiness. They had fewer sleep disruptions, like transitions from deeper to lighter stages. They got about 45 min more of deep sleep at night. They also woke up less frequently at night. After LXB treatment, most people said their overall narcolepsy disease was better. The most common side effects were nausea, dizziness, headache, drowsiness, and vomiting. People with narcolepsy who took LXB had less daytime sleepiness and less disrupted nighttime sleep than before taking LXB.
OBJECTIVE:The efficacy and safety of a highly purified plant-derived cannabidiol (CBD) oral solution (Epidiolex® [US]/Epidyolex® [EU], EPX) have been established for the treatment of seizures in patients with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex. These conditions involve diverse etiologies, suggesting EPX may have broad utility across different seizure types. This systematic literature review (SLR) evaluated studies reporting CBD effectiveness and tolerability in patients with other developmental and epileptic encephalopathies (DEEs) and complex treatment-resistant epilepsies (TREs). METHODS:In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, an SLR was conducted in March 2024 using Embase, PubMed, and Cochrane libraries for publications on complex TREs, CBD, seizure outcomes, and adverse events (AEs). Results were narratively summarized according to epilepsy type. RESULTS:Seizure frequency-related changes were reported in 57 studies including 37 DEEs/TREs comprising 971 patients; most (n = 33) were case reports/small case series. Most common diagnoses were focal/multifocal-onset epilepsy (n = 401) and Angelman syndrome (n = 188). Overall, 47 studies reported seizure frequency reduction in ≥ 1 patient; definitions/thresholds included seizure reduction (n = 18 studies; 20-100 % of patients) and mean/median percent seizure reduction (n = 8 studies; 12-99 % reduction). Twenty-two studies reported ≥ 1 patient was seizure-free for ≥ 48 days. AEs experienced while taking CBD were generally mild or moderate and most commonly gastrointestinal, including diarrhea (17-50 %), decreased appetite (7-45 %), and vomiting (5-86 %). CONCLUSION:CBD may reduce seizure frequency in patients with a range of DEEs and complex TREs. These findings support future studies in these populations.
Study Objectives:National prevalence estimates for idiopathic hypersomnia (IH) are difficult to obtain. This study estimated the diagnosed IH prevalence among US adults. Methods:Symphony Integrated Dataverse claims (01/2015-12/2023) were analyzed. Eligible patients were aged ≥18 years with at least one medical/prescription claim in the year of interest (2019-2023) and prior year. IH was defined by ≥1 medical claim with an IH diagnosis code. Prevalence was estimated among all eligible patients in two ways: annual (IH diagnoses during year of interest) and all-time (IH diagnoses looking back all-time in the database from 2015 through year of interest). Age- and sex-adjusted prevalence estimates were also calculated using the US Census Bureau. Results:Over 179, 182, 193, 205, and 198 million adults were assessed for diagnosed IH prevalence in each respective year 2019-2023. Unweighted annual prevalence of diagnosed IH from 2019 to 2023 was 12.1, 11.1, 11.0, 10.5, and 11.1 per 100 000 persons, respectively. Unweighted all-time lookback prevalence of diagnosed IH from 2019 to 2023 was 32.7, 37.3, 40.6, 43.3, and 49.0 per 100 000 persons, respectively. From 2019 to 2023, estimated standardized numbers of US adults diagnosed with IH were 30 563, 27 975, 27 859, 26 624, and 28 754 based on annual prevalence, and 82 027, 93 768, 101 766, 107 763, and 124 905 based on all-time prevalence. Conclusions:Annual prevalence estimates (i.e. proportions of individuals with diagnosed IH during each year of interest) remained consistent across the follow-up period, ranging from 10.5 to 12.1 per 100 000 persons, signifying the rarity of the diagnosis.
BACKGROUND:Zanidatamab, a dual human epidermal growth factor receptor 2 (HER2)-targeted bispecific antibody, plus chemotherapy both with and without tislelizumab (anti-programmed death 1), showed encouraging efficacy and safety as first-line therapy in phase 2 studies involving patients with HER2-positive gastroesophageal adenocarcinoma. METHODS:In an open-label, phase 3 trial, we randomly assigned, in a 1:1:1 ratio, patients with previously untreated, centrally confirmed HER2-positive advanced gastroesophageal adenocarcinoma to receive zanidatamab and tislelizumab plus chemotherapy, zanidatamab plus chemotherapy, or trastuzumab plus chemotherapy. The two primary end points were progression-free survival and overall survival. RESULTS:At a median follow-up of 25.9 months, progression-free survival was longer with zanidatamab-tislelizumab-chemotherapy (median among 302 patients, 12.4 months) and zanidatamab-chemotherapy (median among 304 patients, 12.4 months) than with trastuzumab-chemotherapy (median among 308 patients, 8.1 months) (hazard ratio for progression or death with zanidatamab-tislelizumab-chemotherapy, 0.63 [95% confidence interval {CI}, 0.51 to 0.78]; hazard ratio with zanidatamab-chemotherapy, 0.65 [95% CI, 0.52 to 0.81]; P<0.001 for both comparisons). Overall survival was longer with zanidatamab-tislelizumab-chemotherapy than with trastuzumab-chemotherapy (median, 26.4 vs. 19.2 months; hazard ratio for death, 0.72; 95% CI, 0.57 to 0.90; P = 0.004). At this interim analysis, overall survival did not differ significantly between zanidatamab-chemotherapy (median, 24.4 months) and trastuzumab-chemotherapy (hazard ratio, 0.80; 95% CI, 0.64 to 1.01; P = 0.06). The incidence of grade 3 or higher adverse events was 83.3% with zanidatamab-tislelizumab-chemotherapy, 73.8% with zanidatamab-chemotherapy, and 74.5% with trastuzumab-chemotherapy; diarrhea was the most common such event, in 24.8%, 20.0%, and 12.9% of patients, respectively. CONCLUSIONS:Zanidatamab plus chemotherapy, both with and without tislelizumab, led to longer progression-free survival than trastuzumab plus chemotherapy among patients with HER2-positive advanced gastroesophageal adenocarcinoma. At this interim analysis, overall survival was longer with zanidatamab-tislelizumab-chemotherapy than with trastuzumab-chemotherapy; further analyses are planned to assess zanidatamab-chemotherapy. Diarrhea was a common adverse event. (Funded by Jazz Pharmaceuticals and others; HERIZON-GEA-01 ClinicalTrials.gov number, NCT05152147.).
