BioCryst Pharmaceuticals, Inc. announces new data from the APeX-S and APeX-2 clinical trials which evaluated oral, once-daily ORLADEYO® (berotralstat) for the prophylactic treatment of HAE demonstrating sustained reductions in attack rates and improvement in quality of life (QoL) among patients living with HAE, highlighting its profile as a well-tolerated, effective and convenient prophylactic HAE therapeutic option.

The company also announces additional analyses from new real-world data that further demonstrate a meaningful reduction in attack rates experienced by patients on ORLADEYO, in addition to findings from a survey that underscore a significant disease and treatment burden among pediatric HAE patients, as reported by their caregivers.

“The final results from the long-term APeX-S study show that ORLADEYO was consistently well-tolerated, with no new safety signals observed, and attack reduction was sustained through 96 weeks. These results are complemented by the analyses from APeX-2, in which clinically meaningful patient-reported improvements in QoL across subgroups was shown at 96 weeks,” says Emel Aygören-Pürsün, M.D., Internal Medicine and Hemostaseology, Division of Oncology, Hematology and Hemostaseology, Department for Children and Adolescents, University Hospital Frankfurt, Germany.

“We are excited to report the final results of our ORLADEYO clinical studies, as these new datasets are being reinforced by what we have observed in the real-world use of ORLADEYO. This real-world evidence supports the continued need for an oral, once-daily option for patients and physicians who are seeking control of their HAE attacks,” says Dr. Ryan Arnold, Chief Medical Officer of BioCryst.

The data are being presented at the 2023 American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting.

The posters being presented at AAAAI include analyses from the APeX-2 and APeX-S clinical studies, as well as real-world data from patients taking ORLADEYO in the United States. APeX-2 was a Phase 3, double-blind, placebo-controlled, parallel-group, three-part study evaluating ORLADEYO versus placebo for the prevention of HAE attacks in patients with HAE Type I or Type II. APeX-S was a Phase 2, open label, international study evaluating the safety and effectiveness of ORLADEYO 110 mg once daily (QD) and 150 mg QD in patients with HAE Type I or Type II for up to 96 weeks in the US and 240 weeks in all other countries.

Overall, treatment-emergent adverse events (TEAEs) reported in APeX-2 and APeX-S were mild and transient, indicating that ORLADEYO was generally well tolerated.

Real-World Outcomes in Patients with HAE Treated with Berotralstat:

  • This analysis assessed patient-reported HAE attack rates of HAE Type I or Type II patients on ORLADEYO 110 mg or 150 mg QD for at least 120 days based on review of data from a sole-source pharmacy from December 2020 to May 2022 (n=213). Baseline attack rates were captured by pharmacist progress notes for the previous 90 days prior to initiation of ORLADEYO and converted to a 30-day average for each patient.
  • Overall, attack rates subsequently decreased upon initiation with ORLADEYO and remained consistently low through 360 days on therapy. The median reported attack rate was ≤0.5 attacks/month across all reporting periods through 360 days, and the median reported attack rate was 0.0 in half of the 30-day reporting periods.
  • These real-world findings suggest that ORLADEYO is a durable and effective long-term prophylactic treatment for patients with HAE.

Disease and Treatment Burden of HAE in Pediatric Patients: Assessment by Caregivers:

  • This analysis focused on a blinded, cross-sectional study based on results from an online survey of U.S. adults (n=35) who self-reported being the caregiver of pediatric HAE Type I or Type II patients (age 2-12 years old). They were asked to share perceptions of their experiences with disease management, current HAE treatments and the potential impact of an oral HAE treatment in pediatric patients.
  • Key findings from the survey included:
  • Only 17 percent of pediatric patients (n=6) were on prophylactic HAE treatment.
    o   40 percent of caregivers (n=14) reported ≥1 attack experienced by the pediatric patient in the past six months.
    o   75 percent of school-age pediatric patients (≥ 5 years old; n=12) who had ≥1 attack missed at least one day of school in the last six months because of HAE and 33 percent missed 6-15 days.
    o   Caregivers of pediatric patients who had ≥1 attack not on prophylactic therapy (n=12) most commonly reported infusion requirements (33 percent) and administration inconvenience (25 percent) as reasons why pediatric patients were not on prophylactic therapy.
    o   These findings demonstrate significant disease and treatment burden experienced by pediatric patients and underscore the need for a more convenient option to help increase adoption of prophylactic treatment for HAE in this patient population.

Long-term HAE Prophylaxis with Berotralstat Is Well Tolerated and Effective: Analysis for the APeX-S Study:

  • This analysis characterizes the final safety and effectiveness results of APeX-S through 96 weeks. Patients (n=387) were initially allocated to once-daily ORLADEYO 110 mg or 150 mg until superior efficacy at 150 mg was demonstrated in APeX-2 and patients on the 110 mg dose at that time transitioned to 150 mg (n=100).
  • No new safety signals were observed. Overall, TEAEs were generally mild and transient, indicating that ORLADEYO was generally well tolerated.
  • Clinically meaningful and sustained reductions in HAE attack rates were observed in patients receiving ORLADEYO 150 mg (n=287). In patients who received ORLADEYO 150 mg, a median attack rate of 0.0 attacks/month was observed in 20 of 24 months. Following one month of ORLADEYO treatment, the mean (SEM) adjusted HAE attack rate was 1.1 (0.1). Subsequently, SEM adjusted HAE attack rates declined to 0.9 (0.1) at Month 6, 0.7 (0.1) at Month 12, and 0.8 (0.1) at Month 24.
  • Patients experienced sustained reductions in attacks throughout treatment through 24 months, consistent with previously reported data, further supporting the long-term safety and effectiveness of ORLADEYO.

Berotralstat Improved Quality of Life through 96 Weeks Across Multiple Subgroups of Patients with HAE:

  • This analysis focused on the changes in QoL assessed in APeX-2 using the validated patient-reported Angioedema Quality of Life Questionnaire (AE-QoL), specifically AE-QoL scores in patients randomized to ORLADEYO 150 mg in part 1 of the study through Week 96 in part 3 of the study (n=40).
  • Results were stratified by four baseline characteristics: age (<35 years old, 35-50 years old, >50 years old); sex (male, female); baseline attack rate (<2 attacks/month, ≥2 attacks/month); prior prophylaxis (prior treatment with androgens or C1 esterase inhibitor). Additionally, AE-QoL results were stratified by the presence or absence of gastrointestinal adverse events (GI AEs) in part 1.
  • Mean patient-reported improvements from baseline to Week 96 in total AE-QoL score exceeded the minimal clinically important difference (MCID) value starting at Week 4 and were sustained through Week 96.
  • Improvements were also observed in all domains of the AE-QoL (functioning, fatigue/mood, fear/shame, nutrition) regardless of stratification, with the largest improvement occurring in the functioning domain in almost all stratification groups.
  • These data illustrate that long-term prophylaxis with ORLADEYO led to sustained and clinically meaningful improvements in patient-reported QoL across multiple subgroups after 96 weeks of treatment, and that patients reported improvements in total AE-QoL score and all AE-QoL domains, regardless of the presence or absence of GI AEs.

(Source: BioCryst)