Topline Results of Phase 3 Investigational Study of VONVENDI™ [von Willebrand factor (recombinant)] Meets Primary Endpoint Effectively Controlling Bleeding and Blood Loss During Surgical Procedures

LEXINGTON, Massachusetts, December 2, 2016 /PRNewswire/ --

Results will form the basis of a supplemental new drug application to the U.S. Food & Drug Administration, requesting an expanded indication for VONVENDI  

Shire plc (LSE: SHP, NASDAQ: SHPG), the leading biotechnology company focused on serving individuals with rare diseases and other highly specialized conditions, today announced topline results from a Phase 3 clinical trial of VONVEND™I [von Willebrand factor (Recombinant)] to treat bleeds in elective surgical settings for adults with severe von Willebrand disease (VWD), the most common inherited bleeding disorder. VONVENDI is an on-demand recombinant treatment for adults living with VWD and replaces von Willebrand factor (VWF), one of several types of proteins in the blood that are needed to facilitate proper blood clotting missing in patients with VWD.^[1] The study met its primary endpoint and indicates that VONVENDI effectively controlled bleeding and blood loss during an operation in adults undergoing major, minor and oral elective surgical procedures. The results will form the basis of a supplemental new drug application to the U.S. Food & Drug Administration, of which Shire is requesting for an expanded indication for VONVENDI.^[2]

"These findings suggest that using VONVENDI to treat bleeds during surgery may offer this patient population a new option designed to help meet individual patient needs during surgery," said Philip J. Vickers, Ph.D., Head of Research and Development, Shire.^[2] "Shire is committed to advancing research and possible care options for patients with VWD, building on our commitment to improve outcomes for patients with a range of bleeding disorders."

The prospective, uncontrolled, open-label, nonrandomized, international, multi-center Phase 3 study enrolled 15 patients 18 years and older diagnosed with severe congenital VWD undergoing major and minor elective surgical procedures. The study assessed the safety and hemostatic efficacy of VONVENDI used before, during or after a surgical procedure, with or without, a recombinant Factor VIII (rFVIII) treatment. Overall hemostatic efficacy was rated as "excellent" or "good" for all 15 treated subjects. A total of 12 treatment emergent adverse events (TEAEs) occurred in six patients during or after infusion treatment. Two serious TEAEs occurred in two patients. Ten non-serious TEAEs occurred in six patients. None of the TEAEs that occurred during the study were assessed as severe allergic reaction. In addition, none of the study subjects developed inhibitory antibodies to VONVENDI, rFVIII or binding antibodies to CHO, rFurin or murine IgG.^[2]

The complete results of the study will be presented at an upcoming medical conference. The results will also be used to support the filing for regulatory approvals in Europe in 2017 and in other markets globally. VONVENDI is also being studied for prophylaxis and pediatric indications.

About von Willebrand disease (VWD) 

VWD is the most common inherited bleeding disorder, affecting up to 1 percent of the U.S. population.^[3] VWD is caused by a deficiency or dysfunction of VWF, one of several types of proteins in the blood that are needed to facilitate proper blood clotting.^[3] Due to this deficiency in VWF, blood is not able to clot effectively in people with VWD, which results in heavy menstrual periods, easy bruising or frequent nose bleeds.^[3] Bleeding caused by VWD is unpredictable and varies greatly among patients with this disease.^[4]

VONVENDI [von Willebrand factor (Recombinant)] Important Information 

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 

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.

For Full Prescribing Information, visit http://www.shirecontent.com/PI/PDFs/VONVENDI_USA_ENG.pdf

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

References 

1. Shire. "Introducing VONVENDI [von Willebrand factor (Recombinant)]." VONVENDI website. http://www.vonvendi.com/about/why-vonvendi/ Accessed November 16, 2016.
2. Data on File. VONVENDI Phase 3 Surgical Study Report.
3. National Hemophilia Foundation. "Von Willebrand Disease." National Hemophilia Foundation website. https://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders/Von-Willebrand-Disease Accessed November 16, 2016.
4. National Hemophilia Foundation. "VWD Summit Highlights." HEMAWARE website. https://hemaware.org/story/vwd-summit-highights Accessed December 1, 2016.

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;
• 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 significant delays, an increase in operating costs, lost product sales, an interruption of research activities or the delay of new product launches;
• 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;
• 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;
• Shire's products and product candidates face substantial competition in the product markets in which it operates, including 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 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;
• failure of a marketed product to work effectively or if such a product is the cause of adverse side effects could result in damage to the Shire's reputation, the withdrawal of the product and legal action against Shire;
• investigations or enforcement action by regulatory authorities or law enforcement agencies relating to Shire'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;
• 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 incurred substantial additional indebtedness to finance the Baxalta acquisition, which may decrease its business flexibility and increase borrowing costs;
• 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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SOURCE Shire plc