VONVENDI, The First and Only Recombinant Treatment for Adults Affected by Von Willebrand Disease, Launches in the U.S.

LEXINGTON, Massachusetts, August 9, 2016 /PRNewswire/ --

Shire plc (LSE: SHP, NASDAQ: SHPG), continuing on Baxalta's long-standing commitment to the bleeding disorder community, today announced the U.S. launch of VONVENDI [von Willebrand factor (Recombinant)], the only recombinant treatment for adults living with von Willebrand disease (VWD).

As the first and only recombinant von Willebrand factor (VWF) treatment, VONVENDI replaces the VWF the body is missing in VWD. The treatment is also the first in the United States that has the option to dose recombinant von Willebrand factor (rVWF) independent of recombinant Factor VIII (rFVIII), based on patient need. This attribute allows for tailored treatment for patients who may not require additional FVIII.

VWD is a hereditary bleeding disorder that is caused by deficiency or dysfunction of VWF, a plasma protein that mediates the initial adhesion of platelets at sites of vascular injury and also carries and protects factor VIII from premature proteolysis. Because of this, the blood does not clot properly, resulting in heavy menstrual periods, easy bruising, or frequent nose bleeds. It is estimated that one in 100 people, approximately 3 million people in the United States, suffer from VWD.

"As the first and only recombinant treatment option, VONVENDI represents an important step forward in the treatment of VWD," said Ralph Gruppo, M.D., Director, Comprehensive Hemophilia and Thrombosis Center at the Cincinnati Children's Hospital. "By being able to replace with only VWF recombinant proteins that function similarly to VWF that occurs naturally in the body, patients and their physicians have an effective new treatment option for this challenging and chronic disease."

With the availability of VONVENDI, Shire continues to grow its industry-leading hematology portfolio, invest in treatment options and support for VWD patients around the world, and aspires to help unite the VWD community to elevate awareness and education. Regulatory submission in Europe is expected in 2017 and in other markets globally. Additionally, VONVENDI is being studied for use in the surgical setting.

"VONVENDI marks a new era in treating von Willebrand disease to help give people with VWD control over their bleeds," said Shannon Resetich, Head of Global Hematology, Shire. "We look forward to expanding availability to patients who can benefit from this treatment all over the world."

VONVENDI was approved by the U.S. Food and Drug Administration (FDA) in December 2015 and is indicated for on-demand treatment and control of bleeding episodes in adults (age 18 and older) with VWD. The FDA approval was based on positive results from a Phase 3 multicenter, open-label clinical trial that assessed the safety, efficacy and pharmacokinetics of VONVENDI with and without recombinant FVIII. In the pivotal study, all participants (100 percent) reported successful treatment of bleeding episodes, with 96.9 percent of treated bleeds (N=192 bleeds in 22 patients) achieving an "excellent" efficacy rating and 3.1 percent achieving a "good" efficacy rating. The most common adverse reaction observed in greater than two percent of patients in clinical trials was generalized pruritus. For more information on VONVENDI, please visit Vonvendi.com.

Important Information for VONVENDI [von Willebrand factor (Recombinant)] 

Indication 

VONVENDI [von Willebrand factor (Recombinant)] is a recombinant von Willebrand factor indicated for on-demand treatment and control of bleeding episodes in adults (age 18 and older) diagnosed with von Willebrand disease.

Detailed Important Risk Information for VONVENDI 

CONTRAINDICATIONS 

VONVENDI is contraindicated in patients who have had life-threatening hypersensitivity reactions to VONVENDI or constituents of the product (tri-sodium citrate-dihydrate, glycine, mannitol, trehalose-dihydrate, polysorbate 80, and hamster or mouse proteins).

WARNINGS AND PRECAUTIONS 

Embolism and Thrombosis 

Thromboembolic reactions, including disseminated intravascular coagulation (DIC), venous thrombosis, pulmonary embolism, myocardial infarction, and stroke, can occur, particularly in patients with known risk factors for thrombosis. Monitor for early signs and symptoms of thrombosis such as pain, swelling, discoloration, dyspnea, cough, hemoptysis, and syncope.

In patients requiring frequent doses of VONVENDI with recombinant factor VIII, monitor plasma levels for FVIII:C activity because an excessive rise in factor VIII levels can increase the risk of thromboembolic complications.

Hypersensitivity Reactions 

Hypersensitivity reactions, including anaphylaxis, may occur. Symptoms can include anaphylactic shock, generalized urticaria, angioedema, chest tightness, hypotension, shock, lethargy, nausea, vomiting, paresthesia, pruritus, restlessness, wheezing and/or acute respiratory distress. If signs and symptoms of severe allergic reactions occur, immediately discontinue administration of VONVENDI and provide appropriate supportive care.

Neutralizing Antibodies 

Neutralizing antibodies (inhibitors) to von Willebrand factor and/or factor VIII can occur. If the expected plasma levels of VWF activity (VWF:RCo) are not attained, perform an appropriate assay to determine if anti-VWF or anti-FVIII inhibitors are present. Consider other therapeutic options and direct the patient to a physician with experience in the care of either von Willebrand disease or hemophilia A.

In patients with high levels of inhibitors to VWF or factor VIII, VONVENDI therapy may not be effective and infusion of this protein may lead to severe hypersensitivity reactions. Since inhibitor antibodies can occur concomitantly with anaphylactic reactions, evaluate patients experiencing an anaphylactic reaction for the presence of inhibitors.

ADVERSE REACTIONS 

The most common adverse reaction observed in ≥2% of subjects in clinical trials (n=66) was generalized pruritus.

Please see VONVENDI full Prescribing Information at http://www.baxalta.com/assets/documents/VONVENDI_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