Shire Granted EU Marketing Authorization for ADYNOVI [Antihemophilic Factor (Recombinant), Pegylated

Shire plc (LSE: SHP, NASDAQ: SHPG), the global biotechnology leader in rare diseases, announced today that the European Commission (EC) has granted Marketing Authorization for ADYNOVI [Antihemophilic Factor (Recombinant), PEGylated], an extended half-life recombinant factor VIII (rFVIII) treatment, for on-demand and prophylactic use in patients 12 years and older living with hemophilia A. ADYNOVI is modified to last longer in the blood and potentially require less frequent injections than unmodified Antihemophilic Factor when used to reduce the frequency of bleeding. It is built on ADVATE^® [Antihemophilic Factor (Recombinant)], a treatment used by hemophilia A patients worldwide for almost 15 years. ADYNOVI's proprietary PEGylation technology, exclusively licensed from Nektar Therapeutics, extends the time between treatments and offers a twice-weekly dosing schedule.¹

"The European approval of ADYNOVI is an important milestone in our continued commitment to provide new treatment options for patients living with hemophilia A," said Dr. Peter Foertig, MD, Global Head Hematology Medical Affairs, Shire. "We believe that the twice-weekly prophylactic dosing, as well as the on-demand control of bleeding, offered by ADYNOVI will bring us closer to our goal of improving and personalizing disease management for hemophilia A patients in Europe."

The Marketing Authorization is based on outcomes from three Phase 3 clinical trials of patients with hemophilia A. These include a prospective, global, multi-center, open label, non-randomized study of patients 12 to 65 years of age; a prospective, uncontrolled, open label, multi-center study of patients 12 years of age and younger; and a study of perioperative control of hemostasis with interim study results from 15 patients with severe hemophilia A undergoing surgical procedures.^2,3,4

Hemophilia A, designated an orphan disease by the EC, is a rare bleeding disorder that causes longer-than-normal bleeding due to lack of proper clotting factor VIII (FVIII) in the blood.^5,6 The severity of hemophilia A is determined by the amount of factor in the blood, with more severity associated with lower amounts of factor.⁷More than half of patients with hemophilia A have the severe form of the condition.⁷Today, hemophilia A affects approximately 150,000 across the globe.⁸ It primarily affects males, with an incidence of one in 5,000 male births.⁹ Of the worldwide hemophilia patient population, an estimated 75 percent lack adequate treatment or access to treatment altogether.⁹

With this approval, Shire is now authorized to market ADYNOVI in the 28 Member States of the European Union (EU), as well as in Iceland, Liechtenstein and Norway.

About ADYNOVI

ADYNOVI was first approved as ADYNOVATE^® [Antihemophilic Factor (Recombinant), PEGylated] by the Food and Drug Administration (FDA) in the U.S. followed by approval in Japan, Canada, and Colombia, and is approved as ADYNOVI in Switzerland. ADYNOVATE most recently received approval in Japan for use in hemophilia A pediatric patients under 12 years of age and those undergoing surgery in November 2017.

ADYNOVI SAFETY INFORMATION FOR EUROPE

Please consult the ADYNOVI Summary of Product Characteristics (SmPC) before prescribing, particularly in relation to dosing and treatment monitoring.

Contraindications

Hypersensitivity to the active substance, to the parent molecule octocog alfa or to any of the excipients listed in the SmPC. Known allergic reaction to mouse or hamster protein.

Special warnings and precautions for use

The medicinal product contains traces of mouse and hamster proteins. If symptoms of hypersensitivity occur, patients should be advised to discontinue use of the medicinal product immediately and contact their physician. Patients should be informed of the early signs of hypersensitivity reactions including hives, generalised urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis.

The formation of neutralising antibodies (inhibitors) against factor VIII is a known complication in the management of individuals with haemophilia A. These inhibitors are usually IgG immunoglobulins directed against the factor VIII procoagulant activity, which are quantified in Bethesda Units (BU) per ml of plasma using the modified assay.

In general, all patients treated with coagulation factor VIII should be carefully monitored for the development of inhibitors by appropriate clinical observations and laboratory tests. If the expected factor VIII activity plasma levels are not attained, or if bleeding is not controlled with an appropriate dose, testing for factor VIII inhibitor presence should be performed.

After reconstitution this medicinal product contains 0.45 mmol sodium (10 mg) per vial.

Adverse Reactions

ADVATE SAFETY INFORMATION FOR EUROPE

ADVATE is contraindicated in patients with known anaphylaxis to mouse or hamster protein or other constituents of the product.

Allergic-type hypersensitivity reactions, including anaphylaxis, are possible and have been reported with ADVATE. Symptoms have manifested as dizziness, paresthesia, rash, flushing, face swelling, urticaria, dyspnea, and pruritus. Discontinue use if hypersensitivity symptoms occur and administer appropriate emergency treatment.

Carefully monitor patients treated with factor VIII products for the development of FVIII inhibitors by appropriate clinical observations and laboratory tests. Inhibitors have been reported following administration of ADVATE predominantly in previously untreated patients (PUPs) and previously minimally treated patients (MTPs).

If expected plasma FVIII levels are not attained, or if bleeding is not controlled with an expected dose, perform an assay that measures FVIII inhibitor concentration.

The serious adverse reactions seen with ADVATE are hypersensitivity reactions and the development of high-titer inhibitors necessitating alternative treatments to FVIII.

The most common adverse reactions observed in clinical trials (frequency greater than or equal to 10 percent of subjects) were pyrexia, headache, cough, nasopharyngitis, vomiting, arthralgia, and limb injury.