Shire Announces FDA Approval of TAKHZYRO™ (lanadelumab-flyo), a First-of-its...
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`(https://www.shire.com/en)
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`Newsroom
`
`Shire Announces FDA Approval of
`TAKHZYRO™ (lanadelumab-flyo), a First-
`of-its-Kind mAb Preventive Treatment for
`Hereditary Angioedema
`
`• In the pivotal study, patients taking TAKHZYRO 300 mg every 2 weeks had an 87% reduction in
`mean monthly attacks vs. placebo (0.26 vs. 1.97, n=27 vs. n=41)
`• All secondary endpoints were met and included reduction in moderate or severe attacks and
`attacks requiring acute treatment
`• According to an exploratory endpoint, there were patients receiving TAKHZYRO 300 mg every 2
`weeks who had zero attacks during the study
`• TAKHZYRO is a subcutaneous injection that took the majority of patients one minute or less to self-
`administer
`
`Dublin, Ireland – August 23, 2018 – Shire plc (LSE: SHP, NASDAQ: SHPG), the leading global
`biotechnology company focused on rare diseases, today announced that following priority review,
`the U.S. Food and Drug Administration (FDA) has approved TAKHZYRO™ (lanadelumab-flyo)
`injection, for prophylaxis to prevent attacks of hereditary angioedema (HAE) in patients 12 years of
`age and older. HAE is a rare, genetic and potentially life-threatening disorder that can result in
`recurrent attacks of edema (swelling) in various parts of the body.
`1,2,3,4
`
`“HAE attacks are painful, debilitating, and potentially life threatening. TAKHZYRO provides the
`HAE community with a new option for the prevention of HAE attacks,” said Anthony J. Castaldo,
`President, U.S. Hereditary Angioedema Association. “We are grateful for the time and effort put
`forth by the patients and researchers who participated in the clinical trial program that enabled this
`important addition to the HAE treatment landscape.”
`
`TAKHZYRO is the only monoclonal antibody (mAb) that provides targeted inhibition of plasma
`kallikrein, an enzyme which is chronically uncontrolled in people with HAE, to help prevent attacks.
`The recommended starting dose of TAKHZYRO is 300 mg every two weeks. A dosing interval of
`300 mg every four weeks is also effective and may be considered if the patient is well-controlled
`(e.g., attack free) for more than six months.
`
`In the Phase III HELP (Hereditary Angioedema Long-term Prophylaxis) Study™ supporting FDA
`approval, TAKHZYRO reduced the number of monthly HAE attacks an average of 87% (n=27) vs.
`placebo (n=41) when administered at 300 mg every two weeks and 73% (n=29) vs placebo (n=41)
`when administered at 300 mg every four weeks (Adjusted P<0.001).
`5
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`CSL EXHIBIT 1057
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`

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`Shire Announces FDA Approval of TAKHZYRO™ (lanadelumab-flyo), a First-of-its...
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`Page 2 of 7
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`In the 26-week clinical study, which included 125 people with HAE, patients taking TAKHZYRO
`300 mg every 2 weeks also had 83% fewer moderate to severe attacks, and 87% fewer attacks
`that needed on-demand treatment. A pre-specified, exploratory analysis showed that 44% of
`patients (n=27) receiving TAKHZYRO 300 mg every two weeks had zero attacks compared to
`placebo (2%, n=41) for the 26-week treatment period from Day 0 to Day 182. Additionally, in a post
`hoc analysis of the 16-week period from Day 70 to Day 182, 77% of patients (n=26) treated with
`TAKHZYRO in the same dosage arm of the trial were attack-free compared to placebo (3%, n=37).
`
`TAKHZYRO has a half-life of approximately two weeks and is administered as one subcutaneous
`self-injection every two weeks at the recommended starting dose. In clinical trials, the majority of
`patients took one minute or less to complete the injection. The most commonly observed adverse
`5
`reactions (≥10% and higher than placebo) associated with TAKHZYRO were injection site
`reactions consisting mainly of pain, erythema, and bruising at the injection site; upper respiratory
`infection; headache; rash; myalgia; dizziness; and diarrhea.
`
`Andreas Busch, Ph.D., Executive Vice President, Head of Research and Development at Shire
`said: “With the approval of TAKHZYRO, HAE patients have an innovative treatment that works
`differently than current options to help prevent attacks. Based on an exploratory and post hoc
`analysis, after six doses of TAKHZYRO 300 mg every two weeks, 77% or nearly 8 of 10 patients
`had zero attacks. This approval reinforces our ongoing commitment to developing novel therapies
`that have a meaningful impact on patients. Looking to the future, we continue to work towards our
`goal of a world in which those living with HAE can aim for zero attacks.”
`
`The FDA approval of TAKHZYRO was based on data from four clinical trials, including the HELP
`Study™, the largest prevention study conducted to date in HAE. Of the patients who completed
`the HELP Study™ who received TAKHZYRO, 97% opted in to an ongoing open-label extension
`study designed to evaluate the long-term safety and efficacy of TAKHZYRO.
`
`Shire added TAKHZYRO to its HAE portfolio with the acquisition of Dyax Corp., which was
`completed in January 2016 in an all cash transaction valued at approximately $5.9 billion. Under
`the terms of the acquisition, the non-tradable contingent value right (CVR) received by Dyax
`shareholders will now pay $4.00 in cash per Dyax share as a result of the FDA approval of
`TAKHZYRO (formerly DX-2930).
`
`About The HELP Study™
`The HELP Study™ was a global, multicenter, randomized, double-blind placebo-controlled parallel
`group trial that evaluated the efficacy and safety of subcutaneously administered TAKHZYRO
`versus placebo over 26 weeks in 125 patients 12 years of age or older with HAE.
`6
`
`The primary endpoint was the number of investigator-confirmed HAE attacks over the entire 26-
`week study duration. TAKHZYRO demonstrated that subcutaneous injections every two or four
`weeks reduced the mean monthly number of attacks across all three TAKHZYRO treatment arms
`studied: 300 mg every two weeks, 300 mg every four weeks, and 150 mg of TAKHZYRO every
`four weeks. At 300 mg every two weeks, TAKHZYRO reduced the number of mean monthly HAE
`6
`attacks by 87% vs. placebo (Adjusted P<0.001).
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`Shire Announces FDA Approval of TAKHZYRO™ (lanadelumab-flyo), a First-of-its...
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`Secondary endpoints included: 1) number of attacks requiring acute treatment and 2) number of
`attacks assessed as moderate or severe. Overall, each TAKHZYRO treatment arm demonstrated
`statistically significant attack rate reductions compared with placebo for all secondary efficacy
`endpoints (Adjusted P<0.001 for all comparisons), including: attacks requiring acute treatment
`(74% to 87%) and moderate or severe attacks (70% to 83%).
`
`The most frequent adverse events occurring in ≥10% of patients taking TAKHZYRO were injection
`site reactions (52%), followed by upper respiratory infection (29%), and headache (21%).
`Hypersensitivity reactions have occurred in few patients (1%) and were non-serious. No
`anaphylaxis and no anaphylactoid reactions have been observed. In case of a severe
`hypersensitivity reaction, patients should discontinue TAKHZYRO and seek appropriate treatment.
`
`The HELP Study™ Extension
`The long-term safety and efficacy of TAKHZYRO for prophylaxis to prevent HAE attacks continues
`to be evaluated in an open-label extension study. The primary objective of the HELP extension
`study is to investigate the long-term safety of TAKHZYRO. At the time of interim analysis, the
`average length of time subjects have been exposed to TAKHZYRO is 8.2 months (SD=2.2).
`Interim safety data is consistent with controlled safety data from the HELP study.
`
`In the extension study, 212 adolescent and adult patients received at least one dose of
`TAKHZYRO. Of these, 109 patients are rollover participants from the HELP Study™ and 103 are
`new or non-rollover participants who had a historical baseline attack rate of >1 attack per 12 weeks
`and a confirmed diagnosis of HAE. The median age of this study population is 43 years with a
`range of 12 to 76.
`
`About TAKHZYRO™ (lanadelumab-flyo) injection
`TAKHZYRO is a fully human monoclonal antibody that specifically binds and decreases plasma
`kallikrein and is indicated for prophylaxis to prevent HAE attacks in patients 12 years and older.
`TAKHZYRO is formulated for subcutaneous administration and has a half-life of approximately two
`weeks. TAKHZYRO is intended for self-administration or administration by a caregiver. The
`7
`patient or caregiver should be trained by a healthcare professional.
`
`U.S. Indication and Important Safety Information
`INDICATION
`TAKHZYRO (lanadelumab-flyo) is indicated for prophylaxis to prevent attacks of hereditary
`angioedema (HAE) in patients ≥12 years of age.
`
`IMPORTANT SAFETY INFORMATION
`Hypersensitivity reactions have been observed. In case of a severe hypersensitivity reaction,
`discontinue TAKHZYRO administration and institute appropriate treatment.
`
`Adverse Reactions: The most commonly observed adverse reactions (≥10% and higher than
`placebo) associated with TAKHZYRO were injection site reactions consisting mainly of pain,
`erythema, and bruising at the injection site; upper respiratory infection; headache; rash; myalgia;
`dizziness; and diarrhea. Less common adverse reactions observed included elevated levels of
`transaminases; one patient discontinued the trial for elevated transaminases.
`
`Use in Specific Populations: The safety and efficacy of TAKHZYRO in pediatric patients <12
`years of age have not been established.
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`Shire Announces FDA Approval of TAKHZYRO™ (lanadelumab-flyo), a First-of-its...
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`No data are available on TAKHZYRO in pregnant women. No data are available on the presence
`of lanadelumab in human milk or its effects on breastfed infants or milk production.
`
`To report SUSPECTED ADVERSE REACTIONS, contact Dyax Corp. (a wholly-owned, indirect
`subsidiary of Shire plc) at 1-800-828-2088, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
`(http://www.fda.gov/medwatch).
`
`Please see full Prescribing Information (http://www.shirecontent.com/?
`product=TAK&countrytype=USA&language=ENG&contenttype=PI).
`
`Shire’s Commitment to Hereditary Angioedema
`HAE is a rare, genetic disorder estimated to affect about 1 in 10,000 to 1 in 50,000 people
`worldwide. The condition results in recurring attacks of edema (swelling) in various parts of the
`1,2
`body, including the abdomen, face, feet, genitals, hands, and throat that can be debilitating and
`painful. Laryngeal attacks that obstruct the airways are potentially life-threatening due to the risk of
`asphyxiation.
`1,3, 4
`
`Shire is a dedicated, long-term partner to the HAE community with a decade of experience
`supporting patients. We are committed to serial innovation in HAE and our portfolio of products
`includes a number of therapy options to help meet the individual 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.
`
`For further information please contact:
`
`Investor Relations
`Christoph
`Brackmann
`
`christoph.brackmann@shire.com
`(mailto:christoph.brackmann@shire.com)
`
`Sun Kim
`
`sun.kim@shire.com (mailto:sun.kim@shire.com)
`
`Scott Burrows
`
`scott.burrows@shire.com (mailto:scott.burrows@shire.com)
`
`Media
`
`Katie Joyce
`
`kjoyce@shire.com (mailto:kjoyce@shire.com)
`
`Emily Bunting
`
`emily.bunting@shire.com (mailto:emily.bunting@shire.com)
`
`+41 41 288 41
`29
`+1 617 588
`8175
`+41 41 288
`4195
`
`+1 781 482
`2779
`+41 79 866
`9703
`
`For all questions related to Dyax CVR, contact American Stock Transfer & Trust Company,
`LLC:
`
`Shareholder Services
`+1 800 937 5449 or out of USA + 1 718 921 8300
`help@astfinancial.com (mailto:help@astfinancial.com)
`www.astfinancial.com (http://www.astfinancial.com)
`
`NOTES TO EDITORS
`Stephen Williams, Deputy Company Secretary, is responsible for arranging the release of this
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`Shire Announces FDA Approval of TAKHZYRO™ (lanadelumab-flyo), a First-of-its...
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`announcement.
`
`Inside Information
`
`This announcement contains inside information.
`
`About Shire
`
`Shire is the global biotechnology leader serving patients with rare diseases and specialized
`conditions. We seek to push boundaries through discovering and delivering new possibilities for
`patient communities who often have few or no other champions. Relentlessly on the edge of
`what’s next, we are serial innovators with a diverse pipeline offering fresh thinking and new hope.
`Serving patients and partnering with healthcare communities in over 100 countries, we strive to be
`part of the entire patient journey to enable earlier diagnosis, raise standards of care, accelerate
`access to treatment, and support patients. Our diverse portfolio of therapeutic areas includes
`Immunology, Hematology, Genetic Diseases, Neuroscience, Internal Medicine, Ophthalmics, and
`Oncology.
`
`Championing patients is our call to action - it brings the opportunity - and responsibility - to change
`people’s lives.
`
`www.shire.com (http://www.shire.com/)
`
`Forward-Looking Statements
`
`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;
`
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`• 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 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 Shire’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 Shire’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;
`• the potential uncertainty among our employees, customers, suppliers, and other business partners
`resulting from the announcement by Takeda Pharmaceutical Company Limited on May 8, 2018 of a
`recommended offer for Shire under the UK Takeover Code; and
`
`a further list and description of risks, uncertainties and other matters can be found in Shire’s most
`recent 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 “ITEM1A: 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.
`
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`Shire Announces FDA Approval of TAKHZYRO™ (lanadelumab-flyo), a First-of-its...
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`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.
`
`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.
`Longhurst HJ, Bork K. Hereditary angioedema: causes, manifestations, and treatment. Br J Hosp
`2
`Med. 2006;67(12):654-657.
`Zuraw BL. Hereditary angioedema. N Engl J Med. 2008;359(10):1027-1036.
`Banerji A. The burden of illness in patients with hereditary angioedema. Ann Allergy Asthma
`Immunol. 2013;111(5):329-336.
`TAKHZYRO™ (lanadelumab-flyo) injection prescribing information. Lexington, MA: Shire LLC;
`5
`2018.
`Banerji A. Lanadelumab for prevention of attacks in hereditary angioedema: results from the
`6
`phase 3 HELP study. American College of Allergy, Asthma and Immunology Meeting. 2017, 74:
`1-18.
`Banerji et al. Inhibiting plasma kallikrein for hereditary angioedema prophylaxis. N Engl J Med.
`7
`2017; 376(8):717-728.
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