ADYNOVATE Phase 3 Efficacy and Safety Data in Children to be Showcased During International Congress of the World Federation of Hemophilia

LEXINGTON, Massachusetts, July 26, 2016 /PRNewswire/ --

Shire plc (LSE: SHP, NASDAQ: SHPG) will present additional data on the clinical experience of ADYNOVATE [Antihemophilic Factor (Recombinant), PEGylated], an extended half-life recombinant Factor VIII (rFVIII) replacement for hemophilia A, during the International Congress of the World Federation of Hemophilia (WFH) in Orlando, Florida. Throughout the Congress, Shire will present more than a dozen scientific updates on the company's broad portfolio of treatments for bleeding disorders, including ADYNOVATE.

"Treatment options that offer the potential of minimizing the impact of this disorder on hemophilia A pediatric patients and their caregivers are needed," said Michael Tarantino, M.D., medical director of the Bleeding & Clotting Disorders Institute. "These data reinforce that ADYNOVATE - a factor replacement treatment with an extended-half life - may help by providing them with a treatment option of twice-weekly dosing."

Hemophilia A is a challenging chronic disease; treatment regimens require regular infusions to reduce the risk of bleeding. Today, hemophilia A affects more than 400,000 people globally and WFH estimates 45 percent of hemophilia A patients in the United States are under the age of 18.

With ADYNOVATE, Shire has expanded its leading hemophilia portfolio with a wide variety of options, helping to further personalize hemophilia A care for pediatric patients. ADYNOVATE is the first extended half-life rFVIII treatment built on a proven protein, ADVATE [Antihemophilic Factor (Recombinant)]. Designed to extend the time FVIII circulates in the body, ADYNOVATE provides dosing flexibility to help achieve personalized treatment goals.

"ADYNOVATE is a great example of building on the proven concept of direct factor replacement and meeting the treatment standards set for hemophilia patients," said Leonard Valentino, M.D., global head, Hematology Medical Affairs, Shire. "We are committed to reducing the burden of hemophilia A for patients of all ages worldwide and look forward to expanding availability of this treatment option to patients who can benefit from its demonstrated safety and efficacy profile."

ADYNOVATE Presentations Illustrate Clinical Profile in Children 

Safety and Efficacy of Pegylated Full-Length Recombinant Factor VIII with Extended Half-Life in Previous Treated Children with Hemophilia A. Poster #: T-P-89 

Data will be presented from a global, open-label Phase 3 study designed to assess the safety and efficacy of a twice-weekly prophylactic ADYNOVATE regimen to control bleeding in previously-treated children under the age of 12. ADYNOVATE met its primary endpoint in the study, as no patients developed inhibitory antibodies to ADYNOVATE. Nearly 40 percent (37.9 percent) of patients experienced no bleeding episodes and more than 70 percent (72.7 percent) of patients had no joint bleeds. Of the bleeding episodes that did occur, none were considered major. The study also assessed the median annualized bleeding rate (ABR), which was 2.0 [mean ABR 3.0 (2.2 - 4.2)]. These comprehensive results reinforce initial data reported from this study in December 2015.

Further analyses from the study to be presented this week investigated characteristics of patients who achieved zero bleeds during the study, as well as an evaluation of reductions in both frequency of dosing (compared to pre-study regimen) and ABRs in patients (<12 years) treated with ADYNOVATE. Following is a synopsis of the analyses to be presented:

• Characteristics of Pediatric Previously Treated Patients with Severe Hemophilia A Aged <12 Years Experiencing No Bleeds During a 6-month Prophylactic Treatment Regimen with Pegylated Recombinant Factor VIII. Poster #:T-P-86
  
  One analysis evaluated the characteristics of patients in the trial who achieved zero bleeds. The study found that 25 of the 66 pediatric (<12 years) patients (37.9 percent) receiving prophylactic treatment with ADYNOVATE achieved zero bleeds. While most characteristics were similar across all participants, patients without bleeding generally had fewer target joints at screening. 
  
• Reduction in Dosing Frequency and ABRs in Previously Treated Pediatric (<12 Years) Patients With Severe Hemophilia a During Prophylactic Treatment With Pegylated Recombinant Factor VIII Compared to Pre-Study Prophylactic Regimen With Other FVIII Concentrates. Poster #: T-P-79 
  
  Another analysis compared dosing frequency and ABRs in previously treated pediatric patients (<12 years). These patients were treated with ADYNOVATE during the study and had been treated prophylactically prior to the study using other FVIII concentrates, such as ADVATE (rFVIII). Twice-weekly prophylactic treatment with ADYNOVATE resulted in reduced dosing frequency in the majority of patients and fewer bleeding episodes. This is based on a reduction in ABRs compared with pre-study prophylactic treatment, while reducing the frequency of infusions in the majority of patients (from three or more times per week).

An Integrated Analysis of Long Term Safety of An extended Half-Life, Pegylated, Full-length Recombinant Factor VIII (BAX 855) in the Treatment of Hemophilia A in 234 Pediatric, Adolescent and Adult Patients. Poster #: T-P-106 

A separate, integrated safety analysis assessed five clinical studies of ADYNOVATE for prophylaxis, bleeding, perioperative management or PK evaluation. Of 234 previously treated hemophilia A pediatric, adolescent and adult patients, the overall rate of AEs/infusion was 2.5 percent (652/25,724), for non-serious AEs 2.4 percent (618/25,724), and for serious AEs 0.1 percent (34/25,724). These data are consistent with the safety profile of ADVATE.

Additional clinical programs supporting ADYNOVATE are underway with the goal of expanding access to this treatment for more patients around the world. Currently, ADYNOVATE is being studied in previously-untreated patients (PUPs) with severe hemophilia A. In parallel, the PROPEL study is in progress to evaluate additional dosing regimens with ADYNOVATE, using pharmacokinetic (PK)-guided prophylaxis among adults with severe hemophilia A. This study is designed to compare outcomes of PK-guided treatment with ADYNOVATE targeting FVIII trough levels of 1-3 percent vs. approximately 10 percent (8-12 percent). Please visit clinicaltrials.gov for more information.

ADYNOVATE was approved in the U.S. in November 2015 and in Japan in March 2016 for use in hemophilia A patients 12 years and older for on-demand treatment and control of bleeding and prophylaxis to reduce the frequency of bleeding episodes. In early 2016, Baxalta, now part of Shire, filed for use in pediatric and surgical settings in the United States. ADYNOVATE is currently under regulatory review in Canada, Switzerland and Europe.

For more information on ADYNOVATE, please visit ADYNOVATE.com.

About ADYNOVATE
ADYNOVATE, [Antihemophilic Factor (Recombinant), PEGylated], is a human antihemophilic factor indicated in adolescent and adult patients (12 years and older) with hemophilia A (congenital factor VIII deficiency) for:

• On-demand treatment and control of bleeding episodes
• Routine prophylaxis to reduce the frequency of bleeding episodes

ADYNOVATE is not indicated for the treatment of von Willebrand disease.

DETAILED IMPORTANT RISK INFORMATION  

CONTRAINDICATIONS
ADYNOVATE is contraindicated in patients who have had prior anaphylactic reaction to ADYNOVATE, to the parent molecule (ADVATE), mouse or hamster protein, or excipients of ADYNOVATE (e.g. Tris, mannitol, trehalose, glutathione, and/or polysorbate 80).

WARNINGS & PRECAUTIONS
Hypersensitivity Reactions
Hypersensitivity reactions are possible with ADYNOVATE. Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with other recombinant antihemophilic factor VIII products, including the parent molecule, ADVATE. Early signs of hypersensitivity reactions that can progress to anaphylaxis may include angioedema, chest tightness, dyspnea, wheezing, urticaria, and pruritus. Immediately discontinue administration and initiate appropriate treatment if hypersensitivity reactions occur.

Neutralizing Antibodies
Formation of neutralizing antibodies (inhibitors) to factor VIII can occur following administration of ADYNOVATE. Monitor patients regularly for the development of factor VIII inhibitors by appropriate clinical observations and laboratory tests. Perform an assay that measures factor VIII inhibitor concentration if the plasma factor VIII level fails to increase as expected, or if bleeding is not controlled with expected dose.

ADVERSE REACTIONS
Common adverse reactions (≥1% of subjects) reported in the clinical studies were headache and nausea.

For Full Prescribing Information, visit http://baxalta.com/assets/documents/ADYNOVATE_PI.pdf 

About ADVATE
ADVATE [Antihemophilic Factor (Recombinant)] is a recombinant antihemophilic factor indicated for use in children and adults with hemophilia A (congenital factor VIII deficiency) for:

• Control and prevention of bleeding episodes
• Perioperative management
• Routine prophylaxis to prevent or reduce the frequency of bleeding episodes

ADVATE is not indicated for the treatment of von Willebrand disease.

DETAILED IMPORTANT RISK INFORMATION  

CONTRAINDICATIONS
ADVATE is contraindicated in patients who have life-threatening hypersensitivity reactions, including anaphylaxis, to mouse or hamster protein or other constituents of the product.

WARNINGS & PRECAUTIONS
Hypersensitivity Reactions
Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with ADVATE. Symptoms include dizziness, paresthesia, rash, flushing, facial swelling, urticaria, dyspnea, pruritus, and vomiting.

Discontinue ADVATE if hypersensitivity symptoms occur and administer appropriate emergency treatment.

Neutralizing Antibodies
Neutralizing antibodies (inhibitors) have been reported following administration of ADVATE predominantly in previously untreated patients (PUPs) and previously minimally treated patients (MTPs). Monitor all patients for the development of factor VIII inhibitors by appropriate clinical observation and laboratory testing. If expected plasma factor VIII activity levels are not attained, or if bleeding is not controlled with an expected dose, perform an assay that measures factor VIII inhibitor concentration.

ADVERSE REACTIONS
Serious adverse reactions seen with ADVATE are hypersensitivity reactions, including anaphylaxis, and the development of high-titer inhibitors necessitating alternative treatments to factor VIII.

The most common adverse reactions observed in clinical trials (frequency ≥5% of subjects) were pyrexia, headache, cough, nasopharyngitis, arthralgia, vomiting, upper respiratory tract infection, limb injury, nasal congestion, and diarrhea.

Please see full prescribing information for ADVATE at: http://www.baxalta.com/assets/documents/ADVATE_PI.pdf  

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:

• disruption from the acquisition and integration of Baxalta Incorporated ("Baxalta") may make it more difficult to conduct business as usual or maintain relationships with patients, physicians, employees or suppliers;
• the company may not achieve some or all of the anticipated benefits of Baxalta's spin-off from Baxter International, Inc. ("Baxter") and the acquisition may have an adverse impact on Baxalta's existing arrangements with Baxter, including those related to transition, manufacturing and supply services and tax matters;
• the failure to achieve the strategic objectives with respect to the acquisition of Baxalta may adversely affect the company's financial condition and results of operations;
• products and product candidates may not achieve commercial success;
• product sales from ADDERALL XR and INTUNIV are subject to generic competition;
• the failure to obtain and maintain reimbursement, or an adequate level of reimbursement, by third-party payers in a timely manner for the company's products may affect future revenues, financial condition and results of operations, particularly if there is pressure on pricing of products to treat rare diseases;
• supply chain or manufacturing disruptions may result in declines in revenue for affected products and commercial traction from competitors; regulatory actions associated with product approvals or changes to manufacturing sites, ingredients or manufacturing processes could lead to significant delays, an increase in operating costs, lost product sales, an interruption of research activities or the delay of new product launches;
• the successful development of products in various stages of research and development 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 the company's ability to sell or market products profitably, and fluctuations in buying or distribution patterns by such customers can adversely affect the company's revenues, financial condition or results of operations;
• investigations or enforcement action by regulatory authorities or law enforcement agencies relating to the company's activities in the highly regulated markets in which it operates may result in significant legal costs and the payment of substantial compensation or fines;
• adverse outcomes in legal matters, tax audits and other disputes, including the company's ability to enforce and defend patents and other intellectual property rights required for its business, could have a material adverse effect on the company's revenues, financial condition or results of operations;
• Shire is undergoing a corporate reorganization and was the subject of an unsuccessful acquisition proposal and the consequent uncertainty could adversely affect the company's ability to attract and/or retain the highly skilled personnel needed to meet its strategic objectives;
• failure to achieve the strategic objectives with respect to Shire's acquisition of NPS Pharmaceuticals Inc. or Dyax Corp. ("Dyax") may adversely affect the company's financial condition and results of operations;
• the company 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 the company's revenues, financial condition or results of operations;
• the company may be unable to retain and hire key personnel and/or maintain its relationships with customers, suppliers and other business partners;
• difficulties in integrating Dyax or Baxalta into Shire may lead to the 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,  Dyax's or Baxalta's filings with the Securities and Exchange Commission, including those risks outlined in "ITEM 1A: Risk Factors" in Shire's and Baxalta's Annual Reports on Form 10-K for the year ended December 31, 2015.

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 republish revised forward-looking statements to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.

FOR FURTHER INFORMATION PLEASE CONTACT:

Investor Relations        
Sarah Elton-Farr
[email protected]
+44-1256-894157

Robert Coates
[email protected]
+44-1256-894874

Ian Karp
[email protected]
+1-781-482-9018   

Media        
Gwen Fisher
[email protected]
+1-781-482-9649

Debbi Ford
[email protected]
+1-617-949-9083

SOURCE Shire plc

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