CUVITRU [Immune Globulin Subcutaneous (Human), 20% Solution] Data Demonstrate Improved Treatment Satisfaction Relative to Patients' Previous Immunoglobulin Therapy

LEXINGTON, Massachusetts, March 6, 2017 /PRNewswire/ --

Shire plc (LSE: SHP, NASDAQ: SHPG), the global leader in rare diseases and highly specialized conditions, will present data assessing primary immunodeficiency (PI) patient treatment satisfaction with CUVITRU [Immune Globulin Subcutaneous (Human), 20% Solution] at the American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting in Atlanta, Georgia, March 3-6, 2017. PI is a group of more than 300 disorders in which part of the body's immune system is missing or does not function properly, in many cases making it more difficult to fight off infections.^[1],[2] It is estimated that as many as six million children and adults may be affected by PI worldwide.^[3]

CUVITRU was approved by the U.S. Food and Drug Administration (FDA) in September 2016, and is the latest addition to Shire's comprehensive immunoglobulin (IG) therapy portfolio. CUVITRU offers a customizable treatment option that can be tailored to patient and physician preference. It is the only 20% subcutaneous IG (SCIG 20%) treatment option with the ability to infuse up to 60 mL (12 grams) per site and up to 60 mL per hour per site, as tolerated.

"Shire is focused on innovating on behalf of patients with PI so they can more easily manage their condition," said Paul Blanchfield, U.S. Head of Immunology, Shire. "CUVITRU allows for fewer infusion sites and shorter infusion durations than other conventional SCIG options, without compromising on efficacy or safety. We hope this means an improved overall treatment experience for PI patients and greater flexibility in managing their condition."

Shire has five poster presentations at AAAAI and will host two symposia featuring clinical immunology experts discussing the importance of customizing PI treatment options to the individual patient and elevating the standard of care.

"Many patients require IG replacement therapy throughout their lives, making it important to consider the patient's experience in addition to the treatment's ability to limit or reduce infections," said Mark R. Stein, MD, FAAAAI, Medical Director at Allergy Associates of the Palm Beaches. "These data advance our understanding of how we can best support patients throughout their PI journey."

Highlights of Shire's Presentations at AAAAI 

Improved Treatment Satisfaction with a New Human Subcutaneous Immunoglobulin (SCIG 20%) in Patients Previously Treated with IVIG 

This analysis compares the treatment satisfaction of patients with PI during the two CUVITRU pivotal studies (North American and European) after the IVIG and CUVITRU treatment period.   Treatment satisfaction was assessed using the Life Quality Index (LQI) instrument following the IVIG and CUVITRU periods among patients who were treated with IVIG prior to the study.  Results demonstrated that after 12 months on CUVITRU, patients reported statistically significant improvements in the Treatment Interference and the Therapy Setting domains of the LQI compared with the IVIG treatment period (3 months) in both the North American and European pivotal studies.  

Analysis of Safety and Tolerability Data in Pediatric Patients with Primary Immunodeficiency Diseases from Two Phase 2/3 Studies of Human Immune Globulin Subcutaneous, 20% 

An analysis of two Phase 2/3 clinical trials of CUVITRU in North America and Europe assessed the combined safety and tolerability data in pediatric patients with PI. A total of 39 patients between the ages of 2 and 16 received weekly CUVITRU infusions for ~1 year. Serious adverse events (SAEs), rates of local/systemic adverse reactions (ARs) defined as causally-related AEs, and infusion characteristics were analyzed. Results demonstrated that CUVITRU was well tolerated at high infusion rates and volumes per site with short infusion durations.

Review of the Onboarding Experience of a New 20% Human Immune Globulin for Subcutaneous Administration (SCIG 20%): Correlation of Infusion Parameters and Adverse Events (AEs) 

Data from a Phase 2/3 North American clinical trial of CUVITRU provided an opportunity to examine the onboarding experience of patients with PI to CUVITRU. In the trial, patients (3-83 years) received weekly CUVITRU infusions for ~1.3 years. As tolerated, volumes up to 60 mL/site and rates up to 60 mL/hr/site were infused, and associations between the rate of causally-related local AEs and the infusion parameters were investigated. Of the 77 patients enrolled, 53 (69%) had no previous SCIG experience. Results showed that the percent of patients who experienced causally-related local AEs during onboarding was low, which decreased and remained low over time. The rate of local AEs was not associated with faster infusion rates or increasing volumes per site with CUVITRU.  

Shire's other data presentations at AAAAI include:

• A New Subcutaneous Immunoglobulin 20% Formulation (SCIG 20%) with Individualized Infusion Parameters Resulted in a Positive Safety and Tolerability Profile in Patients with PIDD in Europe and North America 
• Analyses of a Subset of Patients with Primary Immunodeficiency Diseases (PIDD) who Switched Modes of Administration of Immunoglobulin (Ig) Therapy During Three Consecutive Studies 

In addition to approval of CUVITRU from the FDA, Shire also received successful completion of a decentralized procedure to support approval of CUVITRU by 17 authorities in Europe in June 2016. CUVITRU is now available in the U.S. and Switzerland; the company expects to initiate additional global regulatory submissions for CUVITRU throughout 2017 and 2018.

For more information on CUVITRU, please visit http://www.cuvitru.com.

About Primary Immunodeficiency 

Primary immunodeficiencies (PI) are a group of more than 300 disorders in which part of the body's immune system is missing or does not function properly.^[1] Normally, the immune system protects the body from pathogenic microorganisms like bacteria, viruses, and fungi, which can cause infectious diseases. When any part of a person's immune system is absent or dysfunctional, the individuals are susceptible to infections, and it may take longer to recover from infections. When a defect in the immune system is inherited and genetically determined, it is called primary immune deficiency.^[2] It is estimated that as many as six million children and adults may be affected by PI worldwide.^[3]

About CUVITRU [Immune Globulin Subcutaneous (Human), 20% Solution] 

CUVITRU is an Immune Globulin Subcutaneous (Human) (IGSC), 20% Solution indicated as replacement therapy for primary humoral immunodeficiency (PI) in adult and pediatric patients two years of age and older.

CUVITRU is for subcutaneous infusion only. 

IMPORTANT SAFETY INFORMATION 

BOXED WARNING: THROMBOSIS 

Thrombosis may occur with immune globulin products, including CUVITRU. Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling vascular catheters, hyperviscosity and cardiovascular risk factors. 

For patients at risk of thrombosis, administer CUVITRU at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk of hyperviscosity. 

CONTRAINDICATIONS 

CUVITRU is contraindicated in patients who have had an anaphylactic or severe systemic hypersensitivity reaction to the subcutaneous administration of human immune globulin and in IgA-deficient patients with antibodies against IgA and a history of hypersensitivity to human immune globulin treatment.

WARNINGS and PRECAUTIONS 

Hypersensitivity: Severe hypersensitivity reactions may occur, even in patients who have tolerated previous treatment with human immune globulin. IgA-deficient patients with antibodies to IgA are at greater risk of developing potentially severe hypersensitivity and anaphylactic reactions.

Renal Dysfunction/Failure: Monitor renal function and urine output and consider lower, more frequent dosing in patients who are at risk of developing renal dysfunction because of pre-existing renal insufficiency or predisposition to acute renal failure.

Thrombosis: Monitor for signs and symptoms of thrombosis and assess blood viscosity for those at risk for hyperviscosity.

Aseptic Meningitis Syndrome (AMS): Monitor for clinical signs and symptoms of AMS.

Hemolysis: Monitor for clinical signs and symptoms of hemolysis and delayed hemolytic anemia.

Transfusion-Related Acute Lung Injury (TRALI): Monitor for pulmonary adverse reactions associated with TRALI.

Transmittable Infectious Agents: Because CUVITRU is made from human plasma, it may carry a risk of transmitting infectious agents, such as viruses and other pathogens. No confirmed cases of transmission of viral diseases or variant Creutzfeldt-Jakob disease (vCJD) have been associated with CUVITRU.

Interference with Laboratory Tests: False positive serological test results, with the potential for misleading interpretation, may occur as the result of passively transferred antibodies.

ADVERSE REACTIONS 

The most common adverse reactions observed in clinical trials in ≥ 5% of patients were: local adverse reactions, systemic adverse reactions including headache, nausea, fatigue, diarrhea, and vomiting.

Please see Full Prescribing Information, including Boxed Warning regarding Thrombosis, available at: http://www.shirecontent.com/PI/PDFS/Cuvitru_USA_ENG.pdf.

SHIRE and the Shire Logo are registered trademarks of Shire Pharmaceutical Holdings Ireland Limited or its affiliates. CUVITRU is a trademark or registered trademark of Baxalta Incorporated, a wholly owned, indirect subsidiary of Shire plc.

References 

1. Bousfiha AA et al. The 2015 IUIS Phenotypic Classification for Primary Immunodeficiencies. J Clin Immunol. 2015 Oct;35:727-738.
2. IDF Patient & Family Handbook for Primary Immunodeficiency Diseases. 5th edition. Blaese. 2013.
3. Bousfiha AA et al. Primary immunodeficiency diseases worldwide: more common than generally thought. J Clin Immunol. 2013 Jan;33(1):1-7.

NOTES TO EDITORS 

About Shire 

Shire is the leading global biotechnology company focused on serving people with rare diseases and other highly specialized conditions. We strive to develop best-in-class products, many of which are available in more than 100 countries, across core therapeutic areas including Hematology, Immunology, Neuroscience, Ophthalmics, Lysosomal Storage Disorders, Gastrointestinal / Internal Medicine / Endocrine and Hereditary Angioedema; and a growing franchise in Oncology.

Our employees come to work every day with a shared mission: to develop and deliver breakthrough therapies for the hundreds of millions of people in the world affected by rare diseases and other high-need conditions, and who lack effective therapies to live their lives to the fullest.

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, 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 conducts its own manufacturing operations for certain of its products and is reliant on third party contract manufacturers to manufacture other products and to provide goods and services.  Some of Shire's products or ingredients are only available from a single approved source for manufacture.  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;
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• certain of Shire's therapies involve lengthy and complex processes, which 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;
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• 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 combined company's revenues, financial condition or results of operations;
• inability to successfully compete for highly qualified personnel from other companies and organizations;
• failure to achieve the strategic objectives with respect to Shire's acquisition of NPS Pharmaceuticals, Inc., Dyax Corp. ("Dyax") or Baxalta Inc. ("Baxalta") 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, as well as changes in foreign currency exchange rates and interest rates, that adversely impact the availability and cost of credit and customer purchasing and payment patterns, including the collectability of customer accounts receivable;
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• difficulties in integrating Dyax or Baxalta into Shire may lead to the combined company not being able to realize the expected operating efficiencies, cost savings, revenue enhancements, synergies or other benefits at the time anticipated or at all; and other risks and uncertainties detailed from time to time in Shire's filings with the Securities and Exchange Commission, including those risks outlined in "ITEM 1A: Risk Factors" in Shire's Quarterly Report on Form 10-Q for the quarter ended June 30, 2016.

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.

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