お知らせ • Nov 06
BioCryst Presents New Data at ACAAI Highlighting Burden of HAE on Pediatric Patients and Caregivers and Sustained Reduction of Attacks in Children Treated with One Year of ORLADEYO
BioCryst Pharmaceuticals, Inc. announced new data demonstrating the early and negative psychosocial impact of hereditary angioedema (HAE) and resulting emergency department (ED) and hospital visits on pediatric patients and their caregivers, as well as new one-year data from the ongoing APeX-P clinical trial showing early and sustained reductions in monthly attack rates over one year in pediatric patients with HAE aged 2 to 12 years treated with once-daily ORLADEYO (berotralstat). The New Drug Application (NDA) for an oral granule formulation of once-daily ORLADEYO as prophylaxis in pediatric patients with HAE aged 2 to 12 years is currently under review with the U.S. Food and Drug Administration (FDA), with a target action date of December 12, 2025. The safety and effectiveness of ORLADEYO in pediatric patients <12 years of age have not been established. A capsule formulation of ORLADEYO was approved by the FDA in December 2020 as prophylaxis for patients with HAE aged 12 years and older. ORLADEYO demonstrated early and sustained attack rate reduction, with 65.5% of patients attack-free at month 1 and 70.4% of patients attack-free at month 12. Median attack rate was 0 beginning at month 1 and remained 0 for 11 out of 12 months.ORLADEYO demonstrated high continuation rates: nearly all (93.1%) patients completed =48 weeks of treatment with ORLADEYO.HAE attacks start early in life: median age at diagnosis was 2.0 (0.2-10.0) years with most (82.8%) experiencing HAE symptoms before age 6.ORLADEYO was safe and well tolerated, with no new safety signals identified. The most commonly reported treatment-emergent adverse event (TEAE) was nasopharyngitis. Please see below for full safety information for ORLADEYO. In the APeX-P trial, a 12-week standard-of-care period was followed by a subsequent open-label ORLADEYO treatment period lasting up to a total of 144 weeks. HAE attack rates were assessed over 48 weeks, with safety monitoring continuing for up to 144 weeks. Participants (n=29) were placed into four cohorts by body weight at baseline. The data presented here are from a second interim data cut taken at the time all participants remaining in the study had completed at least 48 weeks of ORLADEYO treatment. Posters #R102, #R109 and #R117 explore psychosocial impacts and disease burden of HAE, as well as HAE treatment experiences, preferences and needs based on feedback collected from caregivers together with their children (31), adolescents (19) and healthcare providers (HCPs) (109) via a combination of video ?in-depth interviews (VIDIs) and online discussions and panels. HAE negatively impacts children and their caregivers in multiple ways: adolescents and caregivers reported that HAE negatively impacts young patients’ mental health, communication with others, and participation in school, sports, and social activities. Compared with caregivers, adolescents indicated a greater impact of HAE on their daily life. Caregivers also reported high negative impact on their own health, including anxiety, stress, disrupted sleep, and neglected self-care. HCPs recognize the negative impacts of HAE: 90% of HCPs reported that HAE attacks distress caregivers and patients, disrupt caregiver and patient daily routines, and negatively impact patients’ quality of life. Most HCPs are concerned that young children with HAE will develop anxiety (84%) or depression (76%) and experience social isolation (76%) or academic underachievement (64%). HAE attacks start early in life: caregivers and adolescents reported symptoms starting at age 5, on average, and HCPs reported that 80% of patients started experiencing symptoms by age 8.HAE attacks occur frequently: caregivers reported that attacks occur about every 3 months and rated HAE as moderately severe (mean of 4.0 on a scale of 1-7).HAE attacks are stressful: negative emotions during attacks (fear, pain, worry) or the limitations associated with them were commonly reported by children and their caregivers. ED/hospital visits are common for young patients with HAE: over three-quarters of adolescents (11/14) and nearly half of caregivers (11/23) reported going to the ED or hospital at least once before age 12. Visits ranged from a few hours to a few days in length.Most adolescents and caregivers have experienced negative ED/hospital experiences: these visits were characterized by treatment delays, medication unavailability, challenges with medication administration, HCPs unfamiliar with HAE, and heightened stress due to the ED/hospital environment. These negative ED experiences are associated with long-term fear of hospitals or needles for some adolescents and children.HCPs also worry about the impact of these ED/hospital visits: nearly three quarters of HCPs surveyed reported concern about their patients receiving inadequate care, treatment-related trauma, and the long-term impact of ED/hospital visits on their patients’ mental health. ORLADEYO (berotralstat) is the first and only oral therapy designed specifically to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years and older. One capsule of ORLADEYO per day works to prevent HAE attacks by decreasing the activity of plasma kallikrein. ORLADEYO (berotralstat) is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 12 years and older. The safety and effectiveness of ORLADEYO for the treatment of acute HAE attacks have not been established. ORLADEYO should not be used for the treatment of acute HAE attacks. Additional doses or dosages of ORLADEYO higher than 150 mg once daily are not recommended due to the potential for QT prolongation. ORLADEYO at a dose of 150 mg is a moderate inhibitor of CYP2D6 and CYP3A4. For concomitant medications with a narrow therapeutic index that are predominantly metabolized by CYP2D6 or CYP3A4, appropriate monitoring and dose titration is recommended. ORLADEYO at a dose of 300 mg is a P-gp inhibitor. Appropriate monitoring and dose titration is recommended for P-gp substrates (eg, digoxin) when coadministering with ORLADEYO.
