Shire Presents Positive Data from Fabry and Gaucher Disease Studies that Continue to Support Patient Switches to REPLAGAL® (agalsidase alfa) and VPRIV® (velaglucerase alfa)

NYON, Switzerland, Aug. 31, 2011 /PRNewswire/ -- Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, today announced positive data from several studies designed to evaluate the safety of switching to REPLAGAL (agalsidase alfa) from Fabrazyme® (agalsidase beta) and the long-term safety and benefits of switching to VPRIV (velaglucerase alfa) from Cerezyme® (imiglucerase). Study results are being presented at the 2011 Annual Symposium of the Society for the Study of Inborn Errors of Metabolism (SSIEM) held from August 30 – September 2 in Geneva, Switzerland.  

"The volume of data presented to the medical community at SSIEM provides compelling evidence of the safety profile and tolerability of REPLAGAL and the long-term clinical efficacy and safety profile of VPRIV," said Dr. M. Rohrbach, MD, PhD from the Division of Metabolism, Connective Tissue Unit, University Children's Hospital in Zurich. "Patients and physicians want to be reassured that the product they are switching to is not only readily available – but also generally well tolerated. The data presented at SSIEM provides us with that evidence."

Data Demonstrate Continued Safety and Tolerability of REPLAGAL for Switch Patients

Six-month data from Shire's HGT-REP-059 study (U.S. treatment protocol) suggest that REPLAGAL at its licensed dose of 0.2 mg/kg every other week is well tolerated by Fabry patients switching from Fabrazyme (agalsidase beta). Safety events observed at six months among the 71 switch patients in this study were similar to those seen historically in those patients treated with REPLAGAL who had not switched from a prior enzyme replacement therapy.

This ongoing study was established to provide U.S. Fabry patients with access to REPLAGAL during the Fabrazyme (agalsidase beta) supply shortage, which has entered its third year. More than 2,600 patients are now being treated with REPLAGAL globally. This figure represents more than 75 percent of the treated Fabry patients worldwide.

Long Term Data Demonstrate Continued Sustained Efficacy and Safety Profile of VPRIV

Additional data from Shire's long-term open-label, Phase I/II TKT025 extension study demonstrate continued improvement of bone mineral density (BMD) with VPRIV. This data show clinically meaningful and statistically significant improvements in lumbar spine BMD which were observed as early as 24 months [Z-score 0.39 (0.06, 0.72)] and femoral neck BMD as early as 33 months [Z-score 0.39 (0.16, 0.62)] in patients on VPRIV (n=10), during year three of therapy and despite significant baseline skeletal pathology.  

Shire also presented data from several other clinical studies that demonstrate the continued sustained efficacy and safety profile of VPRIV in patients switching from Cerezyme (imiglucerase).

About REPLAGAL (agalsidase alfa)

REPLAGAL is a human form of enzyme alpha-galactosidase A (a-Gal A) manufactured in a human cell line by gene activation. 2011 marks the 15th year of clinical experience with REPLAGAL, which is now approved in 46 countries worldwide. REPLAGAL is not currently approved for commercial sale in the U.S.

REPLAGAL is the only human-cell-line-derived form of enzyme replacement therapy (ERT) that is indicated for the long-term treatment of patients with a confirmed diagnosis of Fabry disease (a-Gal A deficiency).

About VPRIV (velaglucerase alfa)

On February 26, 2010, VPRIV was approved by the U.S. FDA as a hydrolytic lysosomal glucocerebroside-specific indicated for long-term enzyme replacement therapy for adult and pediatric patients with type 1 Gaucher disease. On August 26, 2010, the European Commission granted marketing authorization for VPRIV (velaglucerase alfa), for the long-term treatment of type 1 Gaucher disease, making it available in 30 countries across Europe.

VPRIV is for patients who are treatment-naive as well as patients who have previously been treated with imiglucerase.

REPLAGAL Important Safety Information

The most serious adverse reactions seen with REPLAGAL were hypersensitivity reactions. Infusion-related reactions were the most commonly observed adverse reactions in patients treated with REPLAGAL in clinical studies. Most side effects are mild to moderate and include headache, tingling, numbness, tremors, fatigue, change in temperature sensation, increased blood pressure, upset stomach, diarrhea, coughing, sore throat, difficulty sleeping, change in the taste of food, change in smell, difficulty speaking, acne, dry skin and eye problems. About 1 out of 10 patients may have a reaction during or shortly after infusion of REPLAGAL. These effects include chills and facial flushing (warmth and redness).

As with all therapeutic proteins, there is a potential for immunogenicity. Immunoglobulin G (IgG) antibodies appeared to develop following approximately 3 to 12 months of treatment. After 12 to 54 months of therapy, 17% of REPLAGAL-treated patients were antibody positive whereas 7% showed evidence for the development of immunologic tolerance, based on the disappearance of IgG antibodies over time. No immunoglobulin E (IgE) antibodies have been detected in any patient receiving REPLAGAL.

REPLAGAL is not available in all countries and prescribing information may differ between countries.  Please consult your local prescribing information.

VPRIV Important Safety Information

The most serious adverse reactions seen with VPRIV were hypersensitivity reactions. Infusion-related reactions were the most commonly observed adverse reactions in patients treated with VPRIV in clinical studies. The most commonly observed symptoms of infusion-related reactions were: headache, dizziness, low or high blood pressure, nausea, tiredness and weakness, and fever.  Generally the infusion-related reactions were mild and, in treatment-naive patients, onset occurred mostly during the first 6 months of treatment and tended to occur less frequently with time.  

All adult side effects of VPRIV are considered relevant to children (ages 4 to 17 years). Side effects more commonly seen in children compared with adult patients included: upper respiratory tract infection, rash, activated partial thromboplastin time (aPTT) prolonged, and fever. The safety of VPRIV has not been established in patients younger than 4 years of age.

As with all therapeutic proteins, there is a potential for immunogenicity. In the clinical studies, 1 of 54 treatment-naive patients treated with VPRIV developed IgG class antibodies. It is unknown if the presence of IgG antibodies to VPRIV is associated with a higher risk of infusion reactions. 

VPRIV is not available in all countries and prescribing information may differ between countries.  Please consult your local prescribing information. Full prescribing information for VPRIV in the U.S. can be found at www.VPRIV.com.

Notes to editors

SHIRE PLC

Shire's strategic goal is to become the leading specialty biopharmaceutical company that focuses on meeting the needs of the specialist physician. Shire focuses its business on attention deficit hyperactivity disorder (ADHD), human genetic therapies (HGT) and gastrointestinal (GI) diseases; regenerative medicine as well as opportunities in other therapeutic areas to the extent they arise through acquisitions. Shire's in-licensing, merger and acquisition efforts are focused on products in specialist markets with strong intellectual property protection and global rights. Shire believes that a carefully selected and balanced portfolio of products with strategically aligned and relatively small-scale sales forces will deliver strong results.

For further information on Shire including the SmPC, please visit the Company's website: www.shire.com.

"SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995

Statements included herein that are not historical facts 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, the Company's results could be materially adversely affected. The risks and uncertainties include, but are not limited to, risks associated with: the inherent uncertainty of research, development, approval, reimbursement, manufacturing and commercialization of the Company's Specialty Pharmaceutical and Human Genetic Therapies products, as well as the ability to secure and integrate new products for commercialization and/or development; government regulation of the Company's products; the Company's ability to manufacture its products in sufficient quantities to meet demand; the impact of competitive therapies on the Company's products; the Company's ability to register, maintain and enforce patents and other intellectual property rights relating to its products; the Company's ability to obtain and maintain government and other third-party reimbursement for its products; and other risks and uncertainties detailed from time to time in the Company's filings with the Securities and Exchange Commission.  

SOURCE Shire plc