お知らせ • 4m
Takeda Receives U.S. Fda Approval for Orzeyful (Oveporexton) to Treat Narcolepsy Type 1
Takeda announced that the U.S. Food and Drug Administration (FDA) approved ORZEYFUL (oveporexton), an oral orexin receptor 2 (OX2R) agonist, for the treatment of narcolepsy type 1 (NT1, narcolepsy with cataplexy) in adults. The persistent 24-hour nature of NT1 is driven by orexin deficiency and can severely impact people’s lives. As a first-in-class orexin treatment, ORZEYFUL is the only medicine indicated in the U.S. to treat the disease holistically rather than individual symptoms. NT1 is a rare, chronic neurological disease driven by a loss of orexin and affects an estimated 120,000 people in the U.S. People with NT1 experience excessive daytime sleepiness, cataplexy (sudden loss of muscle tone), cognitive symptoms and disrupted nighttime sleep that can severely impact multiple aspects of daily life, including work, education and social interactions. The approval is based on a comprehensive clinical program including the global Phase 3 FirstLight (TAK-861-3001) and RadiantLight (TAK-861-3002) studies that showed oveporexton offers statistically significant improvements across the full range of symptoms of the disease. These included improvements in excessive daytime sleepiness, cataplexy and health-related quality of life. Oveporexton was generally well-tolerated with a safety profile consistent across clinical studies to date. The most common side effects include trouble sleeping (insomnia), urinary urgency, urinary frequency and excessive saliva. The controlled substance classification for ORZEYFUL is currently under review by the Drug Enforcement Administration (DEA) and is expected within 90 days. After the controlled substance classification is determined, ORZEYFUL will be made available through a specialty pharmacy to U.S. healthcare providers and adults living with NT1. The FDA approval is not expected to have a significant impact on the full year consolidated financial forecast for the fiscal year ending March 31, 2027. ORZEYFUL (oveporexton) is an oral orexin receptor 2 (OX2R) agonist, which selectively stimulates the OX2R to restore signaling and address the underlying orexin deficiency associated with narcolepsy type 1 (NT1). By activating OX2Rs, ORZEYFUL promotes wakefulness and reduces abnormal rapid eye movement (REM)-sleep like phenomena, including cataplexy (sudden and temporary loss of muscle tone), to address a range of daytime and nighttime symptoms as evaluated in clinical studies and consistent with the approved label. ORZEYFUL is indicated for the treatment of narcolepsy type 1 (narcolepsy with cataplexy) in adult patients. ORZEYFUL is contraindicated in patients taking strong CYP3A inhibitors. In pooled phase 3 studies in patients with NT1, 60%, 55%, and 1% of patients in the ORZEYFUL 2 mg twice daily, ORZEYFUL 1 mg twice daily, and placebo groups, respectively, developed insomnia. Prior to ORZEYFUL treatment initiation, inform patients about the risk of insomnia at initiation of treatment. If insomnia persists beyond 7 days and significantly impacts daytime functioning or quality of life, consider ORZEYFUL dosage reduction or discontinuation. ORZEYFUL may cause or worsen urinary frequency and urgency. In pooled phase 3 studies in patients with NT1: 58%, 53%, and 5% of patients in the ORZEYFUL 2 mg twice daily, ORZEYFUL 1 mg twice daily, and placebo groups, respectively, developed urinary frequency. 16%, 15%, and 1% of patients in the ORZEYFUL 2 mg twice daily, ORZEYFUL 1 mg twice daily, and placebo groups, respectively, developed urinary urgency. These lower urinary tract symptoms are consistent with ORZEYFUL’s mechanism of action through agonism of the orexin receptor 2 (OX2R) on central micturition pathways. Prior to initiation of ORZEYFUL treatment, inform patients about the risk of urinary frequency and urgency and screen for lower urinary tract symptoms. Monitor ORZEYFUL-treated patients with a history of overactive bladder for worsening urinary tract symptoms. In pooled phase 3 studies in patients with NT1, asymptomatic creatine phosphokinase elevations >5x ULN were observed in 11% (21/196) of ORZEYFUL-treated patients and 5% (4/76) of placebo treated patients. Two of these cases were characterized by markedly elevated CPK and transaminase levels; both patients discontinued treatment. None of the cases were associated with myoglobinuria or renal impairment. Advise patients to report unexplained muscle pain, weakness, or dark urine, particularly when engaging in vigorous physical activity or taking concomitant drugs associated with myotoxicity. The most common adverse reactions (incidence =5% and greater than placebo) reported in phase 3 studies with ORZEYFUL were insomnia, pollakiuria, micturition urgency, and salivary hypersecretion. Concomitant use with strong or moderate CYP3A inhibitors increases oveporexton exposures, which may increase the risk of ORZEYFUL-associated adverse reactions. Concomitant use of strong and moderate CYP3A inducers can increase oveporexton metabolism and decrease plasma levels of oveporexton, which may decrease the effectiveness of ORZEYFUL. There is a pregnancy exposure registry that monitors pregnancy outcomes in women who are exposed to ORZEYFUL during pregnancy. Available data from clinical trials with ORZEYFUL use during pregnancy are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are no data available on the presence of oveporexton in human milk, the effects on the breastfed infant, or the effects on milk production. Animal studies indicate that oveporexton was present in the milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Avoid use of ORZEYFUL in patients with severe hepatic impairment (Child-Pugh C), as it has not been studied in this population. Avoid use of ORZEYFUL in patients with severe renal impairment on dialysis (eGFR).