- FDA assigns an action date of June 20, 2018
- If approved, CINRYZE will be the first and only C1-INH therapy indicated to help prevent HAE attacks from childhood into adulthood
- Shire is the only HAE drug developer to complete pediatric studies for the prophylactic treatment of HAE
CAMBRIDGE, MA – February 15, 2018 – Shire plc (LSE: SHP, NASDAQ: SHPG), the global biotechnology leader in rare diseases, announced today that the U.S. Food and Drug Administration (FDA) accepted the CINRYZE® (C1 esterase inhibitor [human]) supplemental Biologics License Application (sBLA) to expand the currently approved indication to include children aged 6 years and older with hereditary angioedema (HAE). The filing has received Priority Review designation from the FDA, which means CINRYZE has an accelerated review target of eight months, instead of the standard of 12 months. The FDA is expected to provide a decision on the expanded indication of CINRYZE by June 20, 2018, based on the Prescription Drug User Fee Act V action date.
CINRYZE has been approved in the U.S. since October 2008 for routine prophylaxis against attacks in adolescents and adults living with HAE.1 HAE is a rare, genetic disorder that results in recurring attacks of edema (swelling) in various parts of the body, including the abdomen, face, feet, genitals, hands and throat.2,3,4 It is estimated to affect about 1 in 10,000 to 1 in 50,000 people worldwide.5
“Adults and adolescents living with HAE have used CINRYZE to help reduce the frequency and severity of attacks for nearly a decade,” said Jennifer Schranz, Global Development Lead, HAE, Shire. “Shire committed to studying the safety and efficacy of our HAE therapies in children aged 6 years and older because we understand the importance of this work to families in the HAE community. We look forward to working closely with the FDA in the coming months on this important review.”
This sBLA for CINRYZE is supported by data from two open-label studies (LEVP 2006-1 and LEVP 2006-4) and two pediatric clinical studies (0624-203 and 0624-301).6,7,8,9 The pediatric studies used in this filing are the only clinical trials investigating a prophylactic therapy in the HAE pediatric population.
The FDA grants Priority Review designation to drugs that have the potential to provide significant improvements in the safety or effectiveness for the treatment, diagnosis or prevention of a serious disease
CINRYZE is currently approved for routine prophylaxis against angioedema attacks in adolescent and adult patients with HAE. The active substance in CINRYZE is C1-Esterase Inhibitor (C1-INH), which raises plasma levels of C1-INH in patients with HAE, who are prone to swelling due to an underlying deficiency in C1-INH. Treatment with C1-INH addresses the underlying cause of HAE by replacing the deficient protein and helps regulate the production of bradykinin released during an attack. CINRYZE was the first C1-INH proven to help prevent swelling attacks in those living with HAE.1
Shire’s Commitment to Hereditary Angioedema
Shire is a dedicated, long-term partner to the HAE community with nearly a decade of experience supporting patients. We believe people living with HAE deserve a right-fit approach to treatment and are committed to serial innovation. Our existing portfolio of products includes a number of therapy options to help meet the needs of those living with the disease. Beyond our focus on developing novel treatments, we provide specialized services and support offerings tailored to the HAE community. Learn more at shire.com.
CINRYZE INDICATION AND IMPORTANT SAFETY INFORMATION
CINRYZE® (C1 esterase inhibitor [human]) is indicated for routine prophylaxis against angioedema attacks in adolescent and adult patients with Hereditary Angioedema (HAE).
IMPORTANT SAFETY INFORMATION
CINRYZE is contraindicated in patients who have manifested life-threatening immediate hypersensitivity reactions, including anaphylaxis to the product.
Hypersensitivity Reactions: Severe hypersensitivity reactions may occur during or after administration of CINRYZE. Consider treatment methods carefully, because hypersensitivity reactions and HAE attacks may have similar symptoms. In case of hypersensitivity, discontinue CINRYZE infusion and institute appropriate treatment. Have epinephrine immediately available for treatment of an acute severe hypersensitivity reaction.
Thromboembolic Events: Serious arterial and venous thromboembolic (TE) events have been reported at the recommended dose of C1 Esterase Inhibitor (Human) products, including CINRYZE, following administration in patients with HAE. Risk factors may include presence of an indwelling venous catheter/access device, prior history of thrombosis, underlying atherosclerosis, use of oral contraceptives, certain androgens, morbid obesity, and immobility. Benefits of CINRYZE for routine prophylaxis of HAE attacks should be weighed against the risks of TE events in patients with underlying risk factors. Monitor patients with known risk factors for TE events during and after CINRYZE administration.
Transmissible Infectious Agents: Because CINRYZE is made from human blood, it may carry a risk of transmitting infectious agents e.g. viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. ALL infections thought by a physician possibly to have been transmitted by CINRYZE should be reported to Shire Medical Information at 1-800-828-2088.
Adverse Reactions: The only serious adverse reaction observed in clinical studies of CINRYZE was cerebrovascular accident. The most common adverse reactions observed were headache, nausea, rash, and vomiting. Post-marketing adverse reactions include local infusion site reactions and hypersensitivity. Post-marketing thromboembolic events have been reported, including catheter-related and deep venous thrombosis, transient ischemic attack, and stroke.
For additional safety information, click for Prescribing Information and discuss with your doctor.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
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NOTES TO EDITORS
Shire is the global leader in serving patients with rare diseases. We strive to develop best-in-class therapies across a core of rare disease areas including hematology, immunology, genetic diseases, neuroscience, and internal medicine with growing therapeutic areas in ophthalmics and oncology. Our diversified capabilities enable us to reach patients in more than 100 countries who are struggling to live their lives to the fullest.
We feel a strong sense of urgency to address unmet medical needs and work tirelessly to improve people’s lives with medicines that have a meaningful impact on patients and all who support them on their journey.
Statements included herein that are not historical facts, including without limitation statements concerning future strategy, plans, objectives, expectations and intentions, projected revenues, the anticipated timing of clinical trials and approvals for, and the commercial potential of, inline or pipeline products, are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, Shire’s results could be materially adversely affected. The risks and uncertainties include, but are not limited to, the following:
- Shire’s products may not be a commercial success;
- increased pricing pressures and limits on patient access as a result of governmental regulations and market developments may affect Shire’s future revenues, financial condition and results of operations;
- Shire depends on third parties to supply certain inputs and services critical to its operations including certain inputs, services and ingredients critical to its manufacturing processes. Any disruption to the supply chain for any of Shire’s products may result in Shire being unable to continue marketing or developing a product or may result in Shire being unable to do so on a commercially viable basis for some period of time;
- the manufacture of Shire’s products is subject to extensive oversight by various regulatory agencies. Regulatory approvals or interventions associated with changes to manufacturing sites, ingredients or manufacturing processes could lead to, among other things, significant delays, an increase in operating costs, lost product sales, an interruption of research activities or the delay of new product launches;
- the nature of producing plasma-based therapies may prevent Shire from timely responding to market forces and effectively managing its production capacity;
- Shire has a portfolio of products in various stages of research and development. The successful development of these products is highly uncertain and requires significant expenditures and time, and there is no guarantee that these products will receive regulatory approval;
- the actions of certain customers could affect Shire’s ability to sell or market products profitably. Fluctuations in buying or distribution patterns by such customers can adversely affect Shire’s revenues, financial conditions or results of operations;
- failure to comply with laws and regulations governing the sales and marketing of its products could materially impact Shire’s revenues and profitability;
- Shire’s products and product candidates face substantial competition in the product markets in which it operates, including competition from generics;
- Shire’s patented products are subject to significant competition from generics;
- adverse outcomes in legal matters, tax audits and other disputes, including Shire’s ability to enforce and defend patents and other intellectual property rights required for its business, could have a material adverse effect on the Shire’s revenues, financial condition or results of operations;
- Shire may fail to obtain, maintain, enforce or defend the intellectual property rights required to conduct its business;
- Shire faces intense competition for highly qualified personnel from other companies and organizations;
- failure to successfully execute or attain strategic objectives from Shire’s acquisitions and growth strategy may adversely affect the Company’s financial condition and results of operations;
- Shire’s growth strategy depends in part upon its ability to expand its product portfolio through external collaborations, which, if unsuccessful, may adversely affect the development and sale of its products;
- a slowdown of global economic growth, or economic instability of countries in which Shire does business, could have negative consequences for Shire’s business and increase the risk of non-payment by Shire’s customers;
- changes in foreign currency exchange rates and interest rates could have a material adverse effect on Shire’s operating results and liquidity;
- Shire is subject to evolving and complex tax laws, which may result in additional liabilities that may adversely affect the Company’s financial condition or results of operations;
- if a marketed product fails to work effectively or causes adverse side effects, this could result in damage to Shire’s reputation, the withdrawal of the product and legal action against Shire;
- Shire is dependent on information technology and its systems and infrastructure face certain risks, including from service disruptions, the loss of sensitive or confidential information, cyber-attacks and other security breaches or data leakages that could have a material adverse effect on Shire’s revenues, financial condition or results of operations;
- Shire faces risks relating to the expected exit of the United Kingdom from the European Union;
- Shire incurred substantial additional indebtedness to finance the Baxalta acquisition, which has increased its borrowing costs and may decrease its business flexibility;
- Shire’s ongoing strategic review of its Neuroscience franchise may distract management and employees and may not lead to improved operating performance or financial results; there can be no guarantee that, once completed, Shire’s strategic review will result in any additional strategic changes beyond those that have already been announced; and
a further list and description of risks, uncertainties and other matters can be found in this Annual Report on Form 10-K and in Shire’s subsequent Quarterly Reports on Form 10-Q, in each case including those risks outlined in “ITEM 1A: Risk Factors”, and in Shire’s subsequent reports on Form 8-K and other Securities and Exchange Commission filings, all of which are available on Shire’s website.
All forward-looking statements attributable to us or any person acting on our behalf are expressly qualified in their entirety by this cautionary statement. Readers are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof. Except to the extent otherwise required by applicable law, we do not undertake any obligation to update or revise forward-looking statements, whether as a result of new information, future events or otherwise.
1 CINRYZE (C1 Esterase Inhibitor [Human]) Prescribing Information; 2016.
2 Cicardi M, Bork K, Caballero T, et al, on behalf of HAWK (Hereditary Angioedema International Working Group). Evidence-based recommendations for the therapeutic management of angioedema owing to hereditary C1 inhibitor deficiency: consensus report of an International Working Group. Allergy. 2012;67(2):147-157.
3 Zuraw BL. Hereditary angioedema. N Engl J Med. 2008;359(10):1027-1036.
4 Banerji A. The burden of illness in patients with hereditary angioedema. Ann Allergy Asthma Immunol. 2013;111(5):329-336.
5 Longhurst HJ, Bork K. Hereditary angioedema: causes, manifestations, and treatment. Br J Hosp Med. 2006;67(12):654-657.
6 U.S. National Institutes of Health. Open-Label C1 Esterase Inhibitor (C1INH-nf) for the Treatment of Acute Hereditary Angioedema (HAE) Attacks (CHANGE 2). Available at https://clinicaltrials.gov/ct2/show/results/NCT00438815.
7 U.S. National Institutes of Health. Open-Label C1 Esterase Inhibitor (C1INH-nf) for the Prevention of Acute Hereditary Angioedema (HAE) Attacks (CHANGE 3). Available at https://clinicaltrials.gov/ct2/show/results/NCT00462709.
8 U.S. National Institutes of Health. CINRYZE for the Treatment of Hereditary Angioedema Attacks in Children Under the Age of 12. Available at https://clinicaltrials.gov/ct2/show/results/NCT01095510.
9 U.S. National Institutes of Health. Safety and Efficacy Study of CINRYZE for Prevention of Angioedema Attacks in Children Ages 6-11 With Hereditary Angioedema. Available at https://clinicaltrials.gov/ct2/show/NCT02052141?recrs=e&cond=Hereditary+Angioedema&cntry=US&age=0&draw=5&rank=4.