Shire Submits Biologics License Application (BLA) for REPLAGAL(R) With the U.S. Food and Drug Administration (FDA)

Filing Underscores Shire's Ongoing Commitment to Providing U.S. Fabry Patients With an Alternative Treatment Option. Company Recaps velaglucerase alfa Status.

CAMBRIDGE, Massachusetts, December 22 - Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty
biopharmaceutical company, today announced that it has submitted a BLA with
the FDA for REPLAGAL(R) (agalsidase alfa), its enzyme replacement therapy for
Fabry disease. REPLAGAL first received marketing authorization in the
European Union in 2001, and is approved for the treatment of Fabry disease in
45 countries.

REPLAGAL is currently available to U.S. Fabry patients under an
FDA-approved treatment protocol, and the Company is also supporting emergency
IND requests. Shire worked closely with the FDA to establish an early access
program in response to the ongoing shortage of the currently marketed
treatment for Fabry disease in the U.S.

"We continue to deliver on our commitment to the Fabry community by
filing a BLA to support long-term access to REPLAGAL in the United States,"
said Sylvie Gregoire, President of Shire Human Genetic Therapies. "We
understand that this has been a difficult time for patients and we remain
committed to doing all we can to support the Fabry community during the
supply shortage and for the long-term."

Shire expects its REPLAGAL supply to be adequate to meet anticipated
global demand.

Update on Shire's Potential Gaucher Disease Treatment

In light of the supply restrictions on one of the commercially available
products for Gaucher disease during the past six months, Shire has provided
the following update on recent key activities regarding global access to
velaglucerase alfa, its enzyme replacement therapy in development for Type 1
Gaucher disease:

    - The Company has submitted marketing applications for velaglucerase alfa
      in the U.S., EU and Canada. In the U.S., the application is being
      reviewed by the FDA under Priority Review with a PDUFA date of
      February 28, 2010. The CHMP has granted accelerated review for the
      EU MAA.

    - The FDA recently completed the pre-approval inspections of Shire's
      Cambridge and Lexington Massachusetts facilities for the manufacturing
      and testing of velaglucerase alfa. These inspections were an
      important milestone in the review and approval process for the U.S.
      NDA for velaglucerase alfa.

    - Shire continues to work with U.S. physicians to provide access to
      velaglucerase alfa under an FDA-approved treatment protocol. In Europe
      and other countries outside the U.S., patients continue to receive
      the product through pre-approval access programs.

About REPLAGAL(R) (agalsidase alfa)

REPLAGAL is a human form of enzyme alpha-galactosidase A (a-Gal A)
manufactured in a human cell line by gene activation. REPLAGAL is approved in
45 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 (alpha-galactosidase A deficiency).

About Fabry disease

Fabry disease is a lysosomal storage disorder (LSD) that interferes with
the body's ability to break down a specific fatty substance
(globotriaosylceramide or Gb3) which accumulates within the body due to
deficiency of a specific enzyme (alpha-galactosidase A).

Fabry disease affects both males and females and can present with a
number of signs or symptoms of variable degree, such as cardiovascular and/or
renal dysfunction, intense or burning pain, heat intolerance, skin lesions,
gastrointestinal complaints, hearing loss, and ocular problems.

Lifespan is typically reduced in patients with Fabry disease by
approximately 20 years in men and 15 years in women, compared with the
general population.[1,2] The principal causes of death are renal failure,
cardiomyopathy and cerebrovascular events (e.g. stroke).[3]

Fabry disease affects an estimated 8,000 to 10,000 people worldwide.

About Gaucher disease

Gaucher disease is an autosomal recessive disorder caused by mutations
in the GBA gene which results in a deficiency of the lysosomal enzyme
beta-glucocerebrosidase. This enzymatic deficiency causes an accumulation of
glucocerebroside, primarily in macrophages. In this lysosomal storage
disorder (LSD), clinical features are reflective of the distribution of
Gaucher cells in the liver, spleen, bone marrow, skeleton, and lungs. The
accumulation of glucocerebrosidase in the liver and spleen leads to
organomegaly. Bone involvement results in skeletal abnormalities and
deformities as well as bone pain crises. Deposits in the bone marrow and
splenic sequestration lead to clinically significant anemia and
thrombocytopenia.

Gaucher disease is the most prevalent LSD. Gaucher disease has
classically been categorized into 3 clinical types. Type 1 is the most
common; it is distinguished from Type 2 and Type 3 by the lack of early
neurological symptoms. Type 1 Gaucher disease is characterized by variability
in signs, symptoms, severity, and progression.

Shire's velaglucerase alfa program included the largest and most
comprehensive set of Phase III clinical trials conducted to date for Gaucher
disease. Over 100 patients at 24 sites in 10 countries around the world have
participated in the clinical studies.

Velaglucerase alfa is made using Shire's proprietary technology, in a
human cell line. The enzyme produced has the exact human amino acid sequence
and has a human glycosylation pattern.

    References

    1. MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical
       manifestations and impact of disease in a cohort of 60 obligate
       carrier females. J Med Genet 2001;38:769-75.

    2. MacDermot KD, Holmes A, Miners AH. Natural history of Fabry disease in
       affected males and obligate carrier females. J Inherit Metab Dis
       2001;24 Suppl 2:13-14.

    3. Mehta A, Widmer U. Natural history of Fabry disease. In: Mehta A, Beck
       M, Sunder-Plassmann G, editors. Fabry disease: perspectives from 5
       years of FOS. Oxford: Oxford PharmaGenesis Ltd; 2006: p. 183-8.

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 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:
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.

For further information please contact: Investor Relations: Clea Rosenfeld (Rest of the World), +44-1256-894-160; Eric Rojas (North America), +1-617-551-9715; Media: Jessica Mann (Rest of the World), +44-1256-894-280; Jessica Cotrone (North America), +1-781-482-9538