BioCryst Presents New Long-term Data Demonstrating Consistently High Attack-free Status Among Hereditary Angioedema Patients with ORLADEYO® (berotralstat)

Long-term prophylaxis with ORLADEYO continues to help patients achieve consistently high attack-free days regardless of gender, age and prior HAE therapy after 96 weeks of treatment

RESEARCH TRIANGLE PARK, N.C., April 27, 2023 (GLOBE NEWSWIRE) -- BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) today announced new data from the APeX-S clinical trial, which evaluated oral, once-daily ORLADEYO® (berotralstat) for the prophylactic treatment of hereditary angioedema (HAE), showing sustained reduction in disease burden for patients across multiple subgroups through 96 weeks of treatment. The data are being presented at the 13th C1-inhibitor Deficiency & Angioedema Workshop, which is being held in Budapest, Hungary, from May 4-7, 2023.

“We continue to generate evidence that further strengthens confidence in ORLADEYO as a safe, effective and more convenient therapeutic option for people living with HAE. These data demonstrate how our oral, once-daily prophylactic treatment can consistently help patients spend more of their days without disruption from HAE attacks, regardless of their age, gender and experience with prior prophylactic treatment, including among pediatric patients aged 12-17. These additional analyses of long-term data reflect our continued commitment to define the potential benefits and bring ORLADEYO to as many HAE patients around the world as possible,” said Dr. Ryan Arnold, chief medical officer of BioCryst.

BioCryst C1-inhibitor Deficiency & Angioedema Workshop Presentation Highlights

The oral presentation at the C1-inhbitor Deficiency & Angioedema Workshop will include post-hoc analyses from the APeX-S clinical study. APeX-S was a Phase 2, open label, international study evaluating the safety and effectiveness of ORLADEYO 110 mg and 150 mg once daily (QD) in patients with HAE Type I or Type II for up to 96 weeks in the United States and 240 weeks in all other countries. Overall, treatment-emergent adverse events (TEAEs) reported in APeX-S were mild and transient, indicating that ORLADEYO was generally well tolerated.

• Attack-free status across subgroups of patients with hereditary angioedema after 96 weeks of berotralstat treatment: results from the APeX-S trial; Saturday, May 6, 8:00-8:15 am CEST
  • This analysis assessed the attack-free status of patients receiving ORLADEYO 150 mg through 96 weeks in APeX-S (n=287), stratified by baseline age, gender, and prior HAE prophylaxis treatment. The three subgroups included patients who were 12-17 (n=23), 18-64 (n=253) and ≥ 65 years of age (n=11), female (n=180) and male (n=107) and had prior experience with androgens (n=142) or C1-inhibitors (n=105).
  • Overall, a reduction in mean adjusted HAE attack rates was observed compared to Weeks 0-24 in patients treated with ORLADEYO 150 mg QD. Mean adjusted HAE attack rates decreased from 1.08 from Weeks 0-24 (n=287) to 0.69 and 0.59 from Weeks 25-48 (n=214) and Weeks 49-96 (n=158), respectively.
  • Attack-free status was consistently high through 96 weeks of treatment with ORLADEYO 150 mg regardless of patients’ age, gender and prior prophylactic treatment.
    • Patients aged 12-17, 18-64 and ≥ 65 remained attack free an average of 97, 94 and 98 percent of days, with a mean (SEM) of 196.8 (30.4), 99.3 (9.5) and 275.9 (104.4) days and a maximum duration of 461, 1,101 and 1,182 days between attacks, respectively.
    • Female patients remained attack free an average of 94 percent of days, with a mean (SEM) of 106 (11.8) days and a maximum duration of 1,182 days between attacks. Male patients remained attack free an average of 94 percent of days, with a mean (SEM) of 127.2 (17.4) days and a maximum duration of 1,101 days between attacks.
    • Patients who had prior treatment with androgens remained attack free an average of 93 percent of days, with a mean (SEM) of 87.1 (12.7) days and a maximum duration of 1,026 days between attacks. Patients who had prior treatment with C1-inhibitors remained attack free an average of 91 percent of days, with a mean (SEM) of 75.8 (9.8) days and a maximum duration of 584 days between attacks.

• Long-term prophylaxis with ORLADEYO 150 mg led to a durable treatment effect and sustained reduction in disease burden through 96 weeks of treatment regardless of baseline characteristics including patients’ age, gender and prior prophylactic treatment.

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