BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) today announced new real-world data demonstrating rapid, sustained reduction of patient-reported HAE attacks and consistently low attack rates among patients 12 years and older who started on oral, once-daily ORLADEYO (berotralstat) for the prophylactic treatment of hereditary angioedema (HAE), including patients who switched from other prophylactic therapies.
The data are being presented at the 2022 Annual Scientific Meeting of the American College of Allergy, Asthma & Immunology (ACAAI), which is being conducted at the Kentucky International Convention Center in Louisville, Kentucky, from November 10-14, 2022.
These data are particularly exciting because, consistent with our long-term clinical program data, they show that patients on ORLADEYO sustain, and even improve, attack control the longer they are on therapy, said Dr. Ryan Arnold, chief medical officer of BioCryst.
It is notable that this real-world evidence suggests that people living with HAE can maintain or improve control of their disease on ORLADEYO, regardless of prior treatment history, Arnold added.
Every HAE patient has a unique experience with their therapy, and these data demonstrate that ORLADEYO can be a very effective treatment option for patients regardless of their reported prior attack rates or prophylactic therapy history. The sustained, long-term attack rate reductions we are seeing illustrate the durability of this efficacy for patients who are looking to improve control over their HAE by switching to a therapy with a less burdensome route of administration than subcutaneous or intravenous prophylactic therapies, said William R. Lumry, M.D., clinical professor of internal medicine at the University of Texas Southwestern Medical School.
BioCryst ACAAI 2022 Presentation Highlights
The presentations at ACAAI are based on analyses from patient-reported results collected in the real-world clinical setting from BioCrysts sole-source pharmacy, including HAE Type I and Type II patients in the United States who actively received ORLADEYO between December 16, 2020, and May 20, 2022. Consistently Low Hereditary Angioedema Attack Rates Observed with Berotralstat Regardless of Previous Prophylaxis: Real-World Outcomes (poster #P062); Saturday, November 12, 11:35 a.m. ET; Monitor 10, Exhibit Hall
This analysis assessed patient-reported HAE attack rates of patients on ORLADEYO 110 mg or 150 mg who were previously on another prophylactic therapy (n=129), including lanadelumab (n=53), a subcutaneous (SC) C1 esterase inhibitor (n=31), danazol (n=15) and an intravenous (IV) C1 esterase inhibitor (n=21). Nine patients were on a combination of prophylactic therapies.
Regardless of prior prophylaxis, a rapid reduction in median attack rates was observed early (1.67 attacks/month at baseline to a median attack rate of 0.33 attacks/month in days 1-90). The reduction of median attack rates was sustained throughout the 360-day treatment period.
Upon initiating ORLADEYO treatment, the reduction in median attack rates from baseline over the 1360 days period was consistent for patients regardless of their prior prophylaxis therapy. The reductions after starting ORLADEYO for each prior prophylactic therapy were:
77 percent reduction for patients previously on lanadelumab;
64 percent reduction for patients previously on SC C1-INH;
70 percent reduction for patients previously on danazol; and
72 percent reduction previously on IV C1-INH.
The incidence of AEs reported was lower than the incidence reported in clinical trials.
Rapid and Sustained Reductions in Hereditary Angioedema Attack Rates with Long-term Berotralstat: Real-World Outcomes (Distinguished Industry Oral Presentation); Session A; Saturday, November 12, 4:30-5:30 p.m. ET; Room M103-M10
This analysis assessed the efficacy of ORLADEYO 110 mg or 150 mg in patients (n=128) for a treatment period of more than 270 days.
Patients reported a meaningful reduction in HAE attack rates when treated with ORLADEYO. An 80 percent average reduction from median baseline attack rate (1.67 median attacks/month at baseline vs. 0.33 median attacks/month during days 1-90) was observed during the initial 90-day treatment period. Regardless of baseline attack rate, patients reported a reduction in attack rates when treated with ORLADEYO.
The incidence of adverse events (AEs) reported was consistent with the incidence reported in clinical trials.
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
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.
Limitations of use
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.
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. Johns 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 2022 Global Data Point.