BioCryst Pharmaceuticals, Inc. announced new analyses of real-world use of oral, once-daily ORLADEYO(R) (berotralstat) leading to a reduction in monthly attack rates in patients with hereditary angioedema (HAE) who have normal C1-inhibitor (C1-INH) level and function. The company also announced a new post-hoc analysis from the APeX-S clinical trial that showed a sustained reduction in HAE attacks compared to patients' self-reported baseline attack rates. The data are being presented at the 2023 Annual Scientific Meeting of the American College of Allergy, Asthma & Immunology (ACAAI), which is being held at the Anaheim Convention Center in Anaheim, Calif., from November 9-13, 2023.

BioCryst ACAAI 2023 Presentation Highlights The presentations at ACAAI include analyses from the APeX-S clinical study and real-world data from patients taking ORLADEYO in the United States. 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. The real-world data are analyses from patient-reported results collected This analysis assessed patient-reported HAE attack rates for patients with healthcare provider-diagnosed HAE (reflective of an ICD-10 code of D84.1 or T78.3) who have normal C1-INH level and function in the United States and actively received ORLADEYO 110 mg or 150 mg QD at any timepoint between December 16, 2020 and June 15, 2023 (n=302), with data shown for up to 540 days.

Data are also reported for a subset of these patients who reported a 90-day baseline attack rate and received ORLADEYO for >=360 days (n=103). A sizeable number of patients who received another prophylactic treatment for HAE at any time, such as lanadelumab, intravenous and subcutaneous C1-INH and androgens, were included in both cohorts. Patient-reported attack rates were collected by the sole-source pharmacy at baseline and at each refill (approximately every 30 days).

The baseline 30-day average was calculated based on each patient's self-reported attack rate for the 90 days prior to initiating ORLADEYO and by dividing that value by three. Monthly attack rates were calculated by taking the average of the reported attacks across each 90-day period. A reduction in HAE attack rates was observed in both cohorts upon initiation of ORLADEYO: At baseline, the median attack rate was 3.00 attacks per month (n=249).

Upon initiation of ORLADEYO, median attack rates were reduced to 1.00 at Days 1-90 (n=277) and Days 91-180 (n=232); 1.29 at Days 181-270 (n=174); 1.00 at Days 271-360 (n=143); and 1.50 at Days 361-450 (n=105) and Days 451-540 (n=79), with a median attack rate of <=1.50 attacks per month across all reporting periods over the entire duration. -- For patients who reported a 90-day baseline attack rate and received ORLADEYO for >=360 days (n=103), the median baseline attack rate was 3.00 attacks per month. Upon initiation of ORLADEYO, median attack rates were reduced to 1.29 at Days 1-90 (n=100); 1.00 at Days 91-180 (n=99); 1.33 at Days 181-270 (n=99); and 1.00 at Days 271-360 (n=101), with a median attack rate of <=1.33 attacks per month across all reporting periods over the entire duration.

-- This analysis suggests that long-term prophylaxis with ORLADEYO resulted in a reduction in patient-reported monthly attack rates compared to baseline and median patient-reported attack rates remained consistently low in patients with HAE who have normal C1-INH level and function. Berotralstat Reduced Attack Rates Compared to Baseline in Patients with Hereditary Angioedema in APeX-S; ePoster #P064; Saturday, November 11, 12:05-12:20 p.m. PT; Monitor #12, Exhibit Hall This analysis characterized the safety and effectiveness of ORLADEYO 150 mg QD in U.S. patients enrolled in the APeX-S trial who self-reported a baseline attack rate (n=147). Patients were asked to recall the average number of HAE attacks per month (attack rates) they experienced over the six months prior to beginning therapy.

Attack rates after beginning therapy were calculated for each patient based on the number of attacks they experienced that met predefined criteria, as specified in the study protocol, and were adjusted for the duration of treatment in each month. Attack rates at baseline were not evaluated according to the predefined criteria used for inclusion in the effectiveness analysis in APeX-S. ORLADEYO was generally well tolerated, and safety was consistent with that of the entire APeX-S population. In patients who reported HAE attack rates at baseline, mean (SEM) attack rates declined from 2.3 (0.29) self-reported attacks per month prior to initiating ORLADEYO treatment to 0.71 (0.12) at Month 1, 0.49 (0.09) at Month 6 and 0.32 (0.10) at Month 12, respectively.

A median attack rate of 0 attacks per month was observed for all months across the 12-month period. Patients who were treated with ORLADEYO experienced a sustained reduction in HAE attacks compared to their self-reported baseline attack rates, suggesting a reduction in disease burden and durable treatment effect.