Shire Gets FDA Clearance for myPKFiT for Advate to Help Personalize Care for Hemophilia A

Shire receives FDA clearance for myPKFiT™ for Advate® [Antihemophilic Factor (Recombinant)] to help personalize care for hemophilia A

First and only FDA-cleared PK dosing software to support healthcare professionals in creating personalized dosing regimens for patients 16 and older with hemophilia A¹

myPKFiT for ADVATE software availability planned for end of Q1 2018

Cambridge, Ma. – December 19, 2017 – Shire plc (LSE: SHP, NASDAQ: SHPG), the global biotechnology leader in rare diseases, today announced the U.S. Food and Drug Administration (FDA) has granted 510(k) marketing clearance to myPKFiT for ADVATE [Antihemophilic Factor (Recombinant)], a free web-based software that is the first and only FDA-cleared pharmacokinetic (PK) dosing software for hemophilia A patients 16 and older weighing at least 45 kilograms treated with ADVATE. Using as few as two measurable blood samples, myPKFiT for ADVATE generates a patient’s estimated individual PK profile to aid healthcare professionals in personalizing a patient’s prophylaxis ADVATE dose and schedule.

The myPKFiT for ADVATE software represents an innovative approach to estimating a patient’s PK curve, a key measure for assessing drug exposure over time. With myPKFiT for ADVATE, healthcare professionals can estimate a full PK curve with as few as two measurable blood samples, compared to 9 to 11 as recommended by guidelines from the International Society on Thrombosis and Haemostasis (ISTH). Using the patient’s PK curve and additional patient information, healthcare professionals can develop a personalized, PK-guided prophylactic ADVATE treatment regimen tailored to the individual patient’s needs.

“The FDA clearance of myPKFiT for ADVATE marks an important milestone in the personalization of hemophilia care, building on Shire’s strong commitment to continued innovation in hematology,” said Howard B. Mayer, M.D., ad-interim Global Head of Research and Development, Shire.

Hemophilia A, the most common type of hemophilia, is a rare bleeding disorder that causes longer-than-normal bleeding due to lack of clotting factor VIII in the blood. The severity of hemophilia A is determined by the amount of factor in the blood, with more severity associated with lower amounts of factor. More than half of patients with hemophilia A have the severe form of the condition. Hemophilia primarily affects males, with an incidence of one in 5,000 male births in the United States.

“We know patients have complex needs and treatment goals that cannot be met with a one-size-fits-all approach,” said Michael Denne, Head of U.S. Hematology Medical Affairs, Shire. “myPKFiT for ADVATE offers a personalized approach to hemophilia care that allows healthcare professionals to consider their patients’ individual needs and to educate them on their personal PK profiles.”

A version of the myPKFiT for ADVATE software has been CE marked in Europe since 2014.

myPKFiT for ADVATE software is Rx Only. For safe and proper use of the myPKFiT for ADVATE software, please refer to the complete instructions for use in the User Manual when the software is available in the United States, projected to be by the end of Q1 2018.

myPKFiT for ADVATE Indications for Use

The myPKFiT for ADVATE software is intended for use by licensed healthcare professionals (HCPs) who are familiar with hemophilia care. myPKFiT for ADVATE can be used to generate ADVATE dosage and frequency recommendations for routine prophylaxis for an individual patient 16 years of age or older and body weight of 45kg or greater, using that patient’s age and body weight information and local laboratory FVIII one-stage clotting activity measurements of sparse samples collected from that patient. A minimum of two sparse sampling points are required at the recommended 3-4 hours (± 30 minutes) and at 24-32 hours (± 1 hour) post-infusion.

HCPs will also be able to evaluate various prophylaxis dose regimens tailored to an individual patient’s needs and treatment plan. The software output may be used to guide decisions on appropriate ADVATE dose and infusion intervals to maintain FVIII activity levels at or above a user-specified minimum FVIII activity level between 1% and 3% above natural baseline for an individual patient in accordance with FDA approved dosing recommendations provided in the ADVATE Prescribing Information (PI).

myPKFiT for ADVATE should only be used to evaluate prophylactic dosing regiments for hemophilia A patients treated with ADVATE, as per the ADVATE PI. myPKFiT for ADVATE is not indicated for the treatment of von Willebrand disease. myPKFiT for ADVATE should not be used for patients who have developed neutralizing antibody (inhibitor) to FVIII products.

About ADVATE
ADVATE is a full-length (derived from the complete FVIII gene) recombinant FVIII product that is processed without any blood-based additives.

ADVATE is currently approved in 69 countries worldwide, including the United States, Canada, 28 countries in the European Union, Algeria, Argentina, Australia, Brazil, Brunei, Chile, China, Colombia, Ecuador, Hong Kong, Iceland, India, Iraq, Israel, Japan, Kuwait, Macau, Malaysia, Mexico, Morocco, New Zealand, Norway, Panama, Puerto Rico, Qatar, Russia, Saudi Arabia, Serbia, Singapore, South Korea, Suriname, Switzerland, Taiwan, Tunisia, Turkey, Ukraine, Uruguay, and Venezuela.

ADVATE [Antihemophilic Factor (Recombinant)] Important Information

Indications

ADVATE 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.

CONTRAINDICATIONS

Patients who have life-threatening hypersensitivity reactions, including anaphylaxis, to mouse or hamster protein or other constituents of the product.

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 (>5% of subjects) were pyrexia, headache, cough, nasopharyngitis, arthralgia, vomiting, upper respiratory tract infection, limb injury, nasal congestion, and diarrhea.

Please see accompanying ADVATE full Prescribing Information available at http://www.shirecontent.com/PI/PDFs/ADVATE_USA_ENG.pdf

For more information on ADVATE, please visit www.ADVATE.com.