– Additional analysis from APeX-S showed patients who self-reported HAE attack rates at baseline had a median attack rate of 0 attacks per month across 12-month period –
RESEARCH TRIANGLE PARK, N.C., Nov. 10, 2023 (GLOBE NEWSWIRE) -- BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) today announced new analyses of real-world use of oral, once-daily ORLADEYO® (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.
“There is a significant unmet need among people who live with HAE with normal C1-INH, and identifying optimal treatments has been challenging for these patients. These real-world observations suggest ORLADEYO can have a meaningful impact on the lives of people who have HAE with normal C1-INH. We look forward to continuing to evaluate our oral, once-daily prophylaxis as a treatment option for this subpopulation,” said Dr. Ryan Arnold, chief medical officer of BioCryst.
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 ability to compare patients’ treatment outcomes with their HAE attack rates at baseline is tremendously helpful to characterize the impact of a prophylactic therapy. While this analysis from APeX-S includes baseline attack rates that were retrospectively self-reported by patients, the findings are consistent with results previously reported from the pivotal APeX-2 trial, that long-term prophylaxis with ORLADEYO leads to a sustained reduction in attack rates and is an important therapeutic option for the prevention of HAE attacks,” said H. James Wedner, M.D., professor of medicine in the division of allergy and immunology at the John T. Milliken department of medicine at Washington University School of Medicine.
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 in the real-world clinical setting from BioCryst’s sole-source pharmacy.
- Berotralstat Reduced Attack Rates in Patients with Hereditary Angioedema with Normal C1-Inhibitor: Real-World Outcomes; ePoster #P082; Friday, November 10, 5:30-5:45 p.m. PT; Monitor #13, Exhibit Hall
- 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.
In addition to being displayed in the exhibit hall at the noted times, ePosters are accessible online and on demand to registered attendees on ACAAI’s website.
About ORLADEYO® (berotralstat)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.
U.S. Indication and Important Safety Information
INDICATIONORLADEYO® (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.
Limitations of useThe 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.
IMPORTANT SAFETY INFORMATION
An increase in QT prolongation was observed at dosages higher than the recommended 150 mg once-daily dosage and was concentration dependent.
The most common adverse reactions (≥10% and higher than placebo) in patients receiving ORLADEYO were abdominal pain, vomiting, diarrhea, back pain, and gastroesophageal reflux disease.
A reduced dosage of 110 mg taken orally once daily with food is recommended in patients with moderate or severe hepatic impairment (Child-Pugh B or C) and in patients taking chronically administered P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) inhibitors (eg, cyclosporine).
Berotralstat is a substrate of P-gp and BCRP. P-gp inducers (eg, rifampin, St. John’s wort) may decrease berotralstat plasma concentration, leading to reduced efficacy of ORLADEYO. The use of P-gp inducers is not recommended with ORLADEYO.
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.
The safety and effectiveness of ORLADEYO in pediatric patients