Last updated on April 16, 2014 at 17:13 EDT

Shire’s VPRIV® (velaglucerase alfa for injection) Shows Significant Improvement in Gaucher-Related Bone Disease

June 28, 2012

NYON, Switzerland, June 28, 2012 /PRNewswire/ –

Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company,
today presented new data that show VPRIV(R) (velaglucerase alfa for injection), the
company’s enzyme replacement therapy for type 1 Gaucher disease, significantly improved
selected markers of Gaucher-related bone disease in patients. These data were presented at
the European Working Group on Gaucher Disease (EWGGD) meeting held in Paris, France, from
June 28 – 30, 2012.

The data presented demonstrate that VPRIV improves Gaucher-related bone disease by a
sustained increase in bone mineral density (BMD). BMD refers to the measurement of mineral
matter per square centimeter of bone measured by Z-scores. Z-scores allow for a comparison
of a patient’s BMD to age- and sex-matched normalized scores in populations without
Gaucher disease. In Gaucher disease patients, BMD is generally reduced compared to
individuals without Gaucher disease, often resulting in lower Z-scores. Measuring BMD can
help to quantify the impact of Gaucher disease on the patient’s bone and can help identify
the potential benefits of treatment in improving Gaucher-related bone disease.

“Many type 1 Gaucher disease patients experience bone abnormalities,” said Professor
Ari Zimran, Shaare Zedek Medical Center, Hebrew University and Hadassah Medical School,
Jerusalem, Israel. “These study results show that VPRIV is effective in treating selected
markers of Gaucher-related bone disease, allowing these patients to achieve an important
therapeutic goal quickly.”

Results from a head-to-head Phase III study (HGT-GCB-039) of VPRIV and Cerezyme, and
follow-on extension trial (HGT-GCB-044) of VPRIV, demonstrate a statistically significant
improvement in lumbar spine (LS) BMD in Gaucher patients starting at nine months of
treatment with VPRIV (P<0.05). Patients participating in the study were administered 60
U/kg every other week of either VPRIV or Cerezyme for nine months as part of the
HGT-GCB-039 study. All patients, including those who received Cerezyme, subsequently
received 60 U/kg every other week of VPRIV for an additional 15 months in the extension
trial (HGT-GCB-044).

Clinically and statistically significant improvement from baseline in mean LS Z-score
was seen at nine months of treatment with VPRIV, but not in the cohort of patients treated
with Cerezyme. BMD, evaluated as an exploratory endpoint in the Phase III and extension
studies, was measured by dual-energy x-ray absorptiometry (DEXA scan). Median LS Z-scores
at baseline were -1.46 (-3.50, 0.98) in patients treated with VPRIV, and -0.86 (-2.17,
2.02) in patients treated with Cerezyme. Mean changes from baseline in LS Z-scores at nine
months were 0.33 (0.10, 0.55) and 0.06 (-0.22, 0.34), respectively. Following an
additional 15 months of treatment, mean change in LS Z-scores improved to 0.64 (0.22,
1.06) for patients initially treated with VPRIV and improved to 0.54 (0.21, 0.87) for
patients who switched to VPRIV from Cerezyme at nine months. Femoral neck changes from
baseline in both cohorts were non-significant (P>0.05) at either nine or 24 months.
Analysis presented at EWGGD excluded data from five patients on concomitant
bisphosphonates, although similar results were observed when data from these patients were
included. The safety events observed in this study were similar to those seen historically
in patients treated with VPRIV.

Shire presented additional data showing how VPRIV significantly improved
Gaucher-related bone disease in patients at EWGGD:

        - Bone Parameters in Adults with Type 1 Gaucher Disease Treated with
          Velaglucerase Alfa in Trial TKT025 and the Extension Study: Focus on the Bone Marrow
          Burden Scores Over 7 Years: encore presentation
        - Bone Mineral Density in Adults with Type 1 Gaucher Disease Receiving
          Velaglucerase Alfa 60 U/kg Every Other Week: 2-Year Results (HGT-GCB-032/039/044)

About VPRIV:

VPRIV is made in a human cell line using Shire’s gene activation technology. The
enzyme produced has the exact human amino acid sequence as that found in the naturally
occurring human enzyme.

VPRIV is used for the long-term treatment of patients with type 1 Gaucher disease.

VPRIV is approved in 40 countries globally, including the US, the European Union
member states, and Israel, and is for patients previously treated for type 1 Gaucher
disease or those who are treatment-naive.

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, 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 http://www.VPRIV.com.

Notes to editors


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, human genetic therapies, gastrointestinal
diseases and 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, please visit the Company’s website:



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 Pharmaceuticals, Human Genetic Therapies and
Regenerative Medicine products, as well as the ability to secure 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.

For further information please contact:

        Investor Relations
        Eric Rojas                    erojas@shire.com     +1-781-482 0999
        Sarah Elton-Farr              seltonfarr@shire.com +44(0)1256-894157
        Jessica Mann                  jmann@shire.com      +44(0)1256-894-280
        Jessica Cotrone               jcotrone@shire.com   +1-781-482-9538

SOURCE Shire plc

Source: PR Newswire