C1 Esterase Inhibitor (Human)

RESEARCH TRIANGLE PARK, N.C., Feb. 23, 2024 (GLOBE NEWSWIRE) -- BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) today announced new analyses of real-world use of oral, once-daily ORLADEYO® (berotralstat) that showed patients who initiated ORLADEYO experienced rapid, substantial and sustained reductions in attack rates through 18 months of treatment regardless of the severity of their disease, their history of prior prophylaxis or their C1-inhibitor (C1-INH) level and function. The data are being presented in five posters at the 2024 American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting, which is being held at the Walter E. Washington Convention Center in Washington, D.C., from February 23-26, 2024. “These additional analyses of real-world use of ORLADEYO show that any person living with HAE has the potential to experience a rapid, substantial and sustained reduction in their monthly attack rate with ORLADEYO. From patients who live with severe disease to well-controlled patients and those who have a history of being treated with other long-term prophylaxis that carry a therapeutic burden, these data demonstrate that once patients begin oral, once-daily ORLADEYO, they can experience attack control over the duration of their treatment,” said Jonathan Bernstein, M.D., professor of medicine, department of internal medicine, division of allergy & immunology at the University of Cincinnati and partner of the Bernstein Allergy Group and Bernstein Clinical Research Center. Rapid, Substantial and Sustained HAE Attack Rate Reduction After Beginning ORLADEYO Across Multiple Patient Types Three posters (#012; #008; #281) highlight data collected through BioCryst’s sole-source pharmacy that show real-world effectiveness outcomes for patients aged 12 and above with HAE who initiated ORLADEYO in the United States. These analyses present the overall attack rate progression and attack rate progression stratified by severity (i.e., number of attacks at baseline), prior prophylaxis and C1-INH level and function. “We are continuing to see strong disease control with ORLADEYO in the real world, including in patients with HAE who report differing baseline disease severities. These findings further demonstrate that ORLADEYO can help maintain disease control in patients with lower baseline attack rates and further reduce attack rates in patients with more active disease. We continue to be encouraged by the consistent, building body of real-world evidence demonstrating the significant benefit that our oral, once-daily prophylactic therapy can provide to people living with HAE,” said Dr. Ryan Arnold, chief medical officer of BioCryst. Berotralstat Prophylaxis Reduces HAE Attack Rates Regardless of Baseline Attacks: Real-World Outcomes; Poster #012; Friday, February 23, 3:15-4:15 p.m. ET Patients with C1-INH deficiency who received long-term prophylaxis with ORLADEYO achieved rapid reduction in patient-reported monthly HAE attack rates from baseline, regardless of the severity of their disease (n=335).Median attack rates decreased below baseline (1.33 median monthly attack rate) in the first 90 days of ORLADEYO treatment and remained below baseline across all additional 90-day intervals for up to 18 months (540 days) (0.50 median monthly attack rate).Additionally, when stratified by baseline attacks, median monthly attack rates decreased and remained below baseline for up to 540 days on ORLADEYO regardless of their attack rate at baseline. This was observed across patients who reported a 90-day baseline of 0 attacks (0 attacks/month at all time points except for 0.33 at Days 271-360) to those who reported a 90-day baseline of ≥10 attacks (>3.33 attacks/month at baseline to 1.58 attacks/month at Days 1-90, concluding at 1.50 attacks/month at Days 451-540). Consistently Low Hereditary Angioedema Attack Rates with Berotralstat Regardless of Prior Prophylaxis: Real-World Outcomes; Poster #008; Friday, February 23, 3:15-4:15 p.m. ET Patients who initiated ORLADEYO and were previously on at least one other prophylactic therapy at some point during their lifetime (n=216) also experienced rapid, substantial and sustained reductions in HAE attack rates regardless of prior prophylactic therapy, including lanadelumab, subcutaneous (SC) C1-INH and androgens.Of note, the median monthly attack rate for patients who were previously treated with lanadelumab decreased from 1.00 at baseline (n=66) to 0.33 at Days 1-90 (n=71) after initiating ORLADEYO and remained below baseline through Days 451-540 (0.50; n=21). Real-World Effectiveness of Berotralstat in HAE With and Without C1-Inhibitor Deficiency; Poster #281; Saturday, February 24, 9:45-10:45 a.m. ET Similarly, a reduction in monthly HAE attack rates was observed in patients with HAE who have normal C1-INH level and function (n=302) and those with C1-INH deficiency (n=402) upon initiating ORLADEYO.Patients with normal C1-INH had a median attack rate at baseline of 3.00 attacks/month (n=249), which was reduced to 1.00 at Days 1-90 (n=277) and remained below baseline through Days 451-540 (1.50; n=79), while patients with C1-INH deficiency had a median attack rate at baseline of 1.33 attacks/month (n=335), which was reduced to and remained at 0.50 through Days 451-540 (n=119). Methods These posters highlight outcomes collected through BioCryst’s sole-source pharmacy and include patients who actively received ORLADEYO 110 or 150 mg QD from December 16, 2020 to June 15, 2023.Patient-reported attack rates were collected 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.Not all patients reported a baseline attack rate or attack rates during each 90-day period. Real-world Data from French Cohorts Support Safety, Effectiveness and Adherence to ORLADEYO Two additional posters (#028; #023) highlight findings from real-world studies in patients with HAE aged 12 and above in France, including an observational study (BeroLife) and the ongoing prospective MATCH study (Monitoring HAE Treatment Compliance by the community pHarmacist). “These new findings from the BeroLife and MATCH studies indicate an association between adherence to therapy and effectiveness of ORLADEYO. Of note, the results from MATCH show that the number of patients who had high adherence to ORLADEYO after one month of treatment was comparable to the adherence rate among patients who take medications for chronic diseases in France, but this number increased the longer they remained on treatment. Additionally, patients who participated in these studies had a low discontinuation rate, which supports our previously reported findings that the longer patients remain on ORLADEYO, the better their outcomes are,” continued Dr. Ryan Arnold. Assessment of the Tolerability and Effectiveness of Berotralstat for Long-term Prophylaxis in Hereditary Angioedema: BeroLife Study Interim Analysis; Poster #028; Friday, February 23, 3:15-4:15 p.m. ET An interim analysis that shows long-term prophylaxis with ORLADEYO was generally well tolerated and safety was consistent with what has previously been reported from clinical trials. Only 15.6 percent (n=10) experienced a drug-related treatment-emergent adverse event (TEAE), and fewer than 10 percent discontinued ORLADEYO due to a TEAE (n=6).From an effectiveness standpoint, this analysis shows a decrease in HAE attack rates among patients, the majority of whom had already been treated with previous long-term prophylaxis such as attenuated androgens, tranexamic acid and lanadelumab, which is consistent with what was observed in clinical trials with long-term prophylaxis with ORLADEYO. Final data from the BeroLife study are expected later this year. Evaluation of Adherence to Berotralstat in Patients with Hereditary Angioedema: A Prospective Survey in Community Pharmacies; Poster #023; Friday, February 23, 3:15-4:15 p.m. ET An association between adherence and effectiveness of ORLADEYO was observed when taken by patients who received follow-up engagements from a pharmacist each month for six months (n=23).No association was found between adherence to ORLADEYO and the incidence of adverse events. Additionally, no serious drug-related TEAEs occurred and only 12.8 percent of patients (n=6) discontinued treatment during the study. Methods The BeroLife study assesses the safety and effectiveness of ORLADEYO 150 mg QD in a French cohort of patients ages 12 years and older with HAE Type I or Type II (n=64). Data were collected by 18 physician investigators associated with the Reference Centre for Angioedema (CREAK) Expert Network in France from November 2021 to May 2023.The MATCH study assesses the impact of monthly follow-up and therapeutic monitoring by community pharmacists in France on patient adherence to ORLADEYO 150 mg QD (n=47). Adherence is measured using the 8-item Morisky Medication Adherence Scale (MMAS-8), a validated method of determining adherence to treatment through a self-reported measurement of medication-taking behavior. All posters are available to meeting registrants and will be on display in the poster hall in the Walter E. Washington Convention Center (Level 2, Hall D) during the meeting. 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). Berotralstat is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein. 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 <12 years of age have not been established. There are insufficient data available to inform drug-related risks with ORLADEYO use in pregnancy. There are no data on the presence of berotralstat in human milk, its effects on the breastfed infant, or its effects on milk production. To report SUSPECTED ADVERSE REACTIONS, contact BioCryst Pharmaceuticals, Inc. at 1-833-633-2279 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Please see full Prescribing Information. About BioCryst Pharmaceuticals BioCryst Pharmaceuticals is a global biotechnology company with a deep commitment to improving the lives of people living with complement-mediated and other rare diseases. BioCryst leverages its expertise in structure-guided drug design to develop first-in-class or best-in-class oral small-molecule and protein therapeutics to target difficult-to-treat diseases. BioCryst has commercialized ORLADEYO® (berotralstat), the first oral, once-daily plasma kallikrein inhibitor, and is advancing a pipeline of small-molecule and protein therapies. For more information, please visit www.biocryst.com or follow us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements, including statements regarding future results, performance or achievements. These statements involve known and unknown risks, uncertainties and other factors which may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and are subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Some of the factors that could affect the forward-looking statements contained herein include: the ongoing COVID-19 pandemic, which could create challenges in all aspects of BioCryst’s business, including without limitation delays, stoppages, difficulties and increased expenses with respect to BioCryst’s and its partners’ development, regulatory processes and supply chains, negatively impact BioCryst’s ability to access the capital or credit markets to finance its operations, or have the effect of heightening many of the risks described below or in the documents BioCryst files periodically with the Securities and Exchange Commission; BioCryst’s ability to successfully implement its commercialization plans for, and to commercialize, ORLADEYO, which could take longer or be more expensive than planned; the commercial viability of ORLADEYO, including its ability to achieve market acceptance; the FDA or other applicable regulatory agency may require additional studies beyond the studies planned for products and product candidates, may not provide regulatory clearances which may result in delay of planned clinical trials, may impose certain restrictions, warnings, or other requirements on products and product candidates, may impose a clinical hold with respect to product candidates, or may withhold, delay, or withdraw market approval for products and product candidates; BioCryst’s ability to successfully manage its growth and compete effectively; risks related to the international expansion of BioCryst’s business; and actual financial results may not be consistent with expectations, including that revenue, operating expenses and cash usage may not be within management's expected ranges. Please refer to the documents BioCryst files periodically with the Securities and Exchange Commission, specifically BioCryst’s most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K, which identify important factors that could cause the actual results to differ materially from those contained in BioCryst’s forward-looking statements. BCRXW Contact:John Bluth+1 919 859 7910jbluth@biocryst.com

- TAKHZYRO® is the First Routine Prevention Treatment of HAE Approved in the EU for Patients Under the Age of Six. - The therapeutical indication for TAKHZYRO® has been extended to patients aged 2 years and older .1 - O ffers a New Preventative Treatment Option for young HAE patients with high unmet need ZURICH, Nov. 17, 2023 /PRNewswire/ -- Takeda (TSE:4502/NYSE:TAK) today announced the European Commission has approved TAKHZYRO® (lanadelumab) for the routine prevention of recurrent attacks of Hereditary Angioedema (HAE) in patients aged 2 years and older1, expanding its initial approved use and making it the first long-term prophylactic treatment of HAE available in European Economic Area for patients under the age of six.2,3,4 The recently approved extension of the indication in paediatric patients was paired with an additional strength of 150 mg for Lanadelumab solution for injection in pre-filled syringe. TAKHZYRO® 150mg should be used in patients aged 2 years and older and weighing less than 40 kg to prevent angioedema attacks in patients with Hereditary Angioedema (HAE).1 Previously indicated for the routine prevention of recurrent attacks of HAE in patients aged 12 years and older in the EEA5, the update is supported by clinical data from Phase 3 Study SHP643-3016, in combination with extrapolation of data from the pivotal Adult and Adolescent Study DX-2930-037, and by quality data supporting the new 150 mg pre-filled syringe formulation8. Overall, the safety and efficacy of TAKHZYRO® in preventing Hereditary Angioedema (HAE) attacks in paediatric patients aged 2 and above was demonstrated and the benefit risk-balance was considered positive. The EMA is the second Agency recommending approval in paediatric population 2 years of age and older, following the U.S. Food and Drug Administration's (FDA) approval of the supplemental Biologics License Application (sBLA) in February this year, for the same expanded use of TAKHZYRO® (lanadelumab-flyo).9 "Potentially fatal upper airway angioedema has been reported in patients as young as 3 years old10, presenting an acute unmet need in some of the most vulnerable of HAE patients." said Didier Relin, Head of International Regulatory at Takeda. "With this expanded label, TAKHZYRO® offers a welcomed new preventative treatment option for the paediatric HAE patient population, and one that can be administered at home with the support of a trained caregiver." Notes to editors: European Commission Decision number: EMEA/H/C/004806/X/0034/G About HAE Hereditary angioedema (HAE) is a rare genetic disorder that results in recurring attacks of oedema – swelling – in various parts of the body, including the abdomen, face, feet, genitals, hands and throat. The swelling can be debilitating and painful.11 Attacks that obstruct the airways can cause asphyxiation and are potentially life threatening.12 HAE affects an estimated 1 in 50,000 people worldwide.13 It is often under recognised, under diagnosed and under treated.11 HAE, like so many other rare diseases, is highly complex, and patients, their families and caregivers often undergo years of strain trying to understand their disease, get a definitive diagnosis and gain access to the medicines they need. At Takeda we are a committed champion for the patients we serve. Every individual living with HAE is unique and by listening and reacting to their needs, we translate the insights we gain into innovative solutions – from diagnosis to ongoing management. Advancing the science is crucial to the way we operate and we are bold in our mission to accelerate diagnosis and develop treatments that will make a difference to the lives of HAE patients, their support networks and those medical professionals who care for them. About Lanadelumab (TAKHZYRO®) Lanadelumab is a fully human monoclonal antibody that specifically binds and decreases plasma kallikrein and is indicated for routine prevention of recurrent attacks of HAE in patients aged 2 years and older. It was studied in one of the largest prevention studies in HAE with the longest active treatment duration, and Lanadelumab consistently demonstrated HAE attack reduction. Lanadelumab is formulated for subcutaneous administration and has a half-life of approximately two weeks. Lanadelumab is intended for self-administration or administration by a caregiver once trained by a healthcare professional.5 About Study SHP643-301 (SPRING Study) SHP643-301 is A Multicenter, Open-Label Phase 3 Study to Evaluate Safety, PK, Pharmacodynamics, And Clinical Activity/Outcomes of TAKHZYRO® (lanadelumab) for Prevention Against Acute Attacks of HAE in Pediatric Patients 2 To <12 Years of Age. The safety profile was consistent with that seen in the clinical program for patients 12 years of age and older; there were no serious adverse events and no dropouts due to adverse events. The study also successfully reached the secondary objective evaluating the clinical activity/outcome of TAKHZYRO in preventing hereditary angioedema (HAE) attacks as well as characterizing the pharmacodynamics of TAKHZYRO in paediatric patients 2 to <12 years of age.6 About Takeda Pharmaceutical Company Takeda is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to discover and deliver life-transforming treatments, guided by our commitment to patients, our people and the planet. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Rare Genetics and Hematology, Neuroscience, and Gastroenterology (GI). We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people's lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries and regions. Important Notice For the purposes of this notice, "press release" means this document, any oral presentation, any question-and-answer session and any written or oral material discussed or distributed by Takeda Pharmaceutical Company Limited ("Takeda") regarding this release. This press release (including any oral briefings and any question-and-answer in connection with it) is not intended to, and does not constitute, represent or form part of any offer, invitation or solicitation of any offer to purchase, otherwise acquire, subscribe for, exchange, sell or otherwise dispose of, any securities or the solicitation of any vote or approval in any jurisdiction. 1 (23)01019-X/pdf#:~:text=How%20does%20this%20study%20impact,prophylaxis%20in%20this%20age%20group. 2 HAEGARDA® (C1 Esterase Inhibitor Subcutaneous [Human]). Product Characteristics. 3 CINRYZE® (C1 esterase inhibitor [human]). Product Characteristics. 4 Farkas, H., Martinez–Saguer, I., Bork, K., Bowen, T., Craig, T., Frank, M., ... & Zuraw, B. (2017). International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency. Allergy, 72(2), 300-313. 5 European Medicines Agency, TAKHZYRO Summary of Product Characteristics. Available at: Last Accessed: November 2023. 6 Maurer M, Lumry WR, Li H, et al. Efficacy and Safety of Lanadelumab in Pediatric Patients Aged 2 to <12 years With Hereditary Angioedema: Results From the Open-Label, Multicenter Phase 3 SPRING Study. Abstract submitted to European Academy of Allergy and Clinical Immunology Hybrid Congress 2022. 7 8 . 9 TAKHZYRO®(lanadelumab-flyo) injection. U.S. Prescribing Information. 10 Bork, K., Hardt, J., Schicketanz, K. H., & Ressel, N. (2003). Clinical studies of sudden upper airway obstruction in patients with hereditary angioedema due to C1 esterase inhibitor deficiency. Archives of Internal Medicine, 163(10), 1229-1235. 11 Mau rer, M., Magerl, M., et al. (2022). The international WAO/EAACI guideline for the management of hereditary angioedema—The 2021 revision and update. Allergy, 77(7), 1961–1990. . 12 Banerji, A., Davis, K. H., Brown, T. M., Hollis, K., Hunter, S. M., Long, J., ... & Devercelli, G. (2020). Patient-reported burden of hereditary angioedema: findings from a patient survey in the United States. Annals of Allergy, Asthma & Immunology, 124(6), 600-607. 13 Longhurst, H. J., & Bork, K. (2019). Hereditary angioedema: an update on causes, manifestations and treatment. British Journal of Hospital Medicine, 80(7), 391-398. Logo -