FDA Advisory Committee Strongly Recommends Approval and Self-Administration of FIRAZYR® (icatibant) for the Treatment of Acute Attacks of Hereditary Angioedema

June 23, 2011

DUBLIN, Ireland and LEXINGTON, Massachusetts, June 23, 2011 /PRNewswire/ –

Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty
biopharmaceutical company, today announced that the Pulmonary-Allergy Drugs
Advisory Committee to the U.S. Food and Drug Administration (FDA)
recommended, by a vote of twelve to one, that the efficacy and safety data
provides substantial evidence to support approval of FIRAZYR(R) (icatibant)
for the treatment of acute attacks of hereditary angioedema (HAE) in
patients 18 years and older. In addition, by a vote of eleven to one, with
one abstention, the Committee recommended self-administration of the drug by

The Committee’s input will be considered by the FDA in its review of the
New Drug Application for FIRAZYR. The FDA is not bound by the Committee’s
guidance, but takes its advice into consideration when reviewing
investigational medicines. The Company has been assigned an action date of
August 25, 2011 under the Prescription Drug User Fee Act.

“Due to the unpredictable and potentially life-threatening nature of HAE
attacks, we believe that self-administration of FIRAZYR can represent an
effective and convenient treatment for patients to better manage their
disease,” said Sylvie Gregoire, President of Shire HGT. “We will continue to
work closely with the FDA as it prepares to make its final decision on the
FIRAZYR application.”

In considering whether FIRAZYR is safe and effective, the Committee
considered data from three double-blind, randomized, controlled phase III
trials, known as the FAST-1, FAST-2, and FAST-3 studies. The results from
these trials, which included patients with cutaneous, abdominal, and
laryngeal attacks, provided substantial and convincing evidence of
clinically meaningful benefit of FIRAZYR for the treatment of acute HAE
attacks in adults. Treatment of acute attacks with 30 mg of FIRAZYR
administered subcutaneously was generally well tolerated with a consistent
safety profile across all clinical studies. Key study symptom measures
included time to onset of symptom relief, based on measures of abdominal
pain, skin pain, skin swelling, and measured time to a clinically relevant
effect for the primary (main) symptom of attack from the patient’s

In FAST-3, FIRAZYR provided a statistically significant and clinically
meaningful benefit relative to placebo for the primary endpoint of time to
onset of symptom relief, which was defined as a 50% reduction in a composite
symptom score assessed by the patient. The median time to onset of symptom
relief for FIRAZYR by this measure was 2.0 hours, compared with 19.8 hours
for placebo. FIRAZYR also provided a significantly shorter time to onset of
symptom relief for the patient’s primary symptom. The median time to onset
of relief for FIRAZYR by this measure was 1.5 hours, compared with 18.5
hours for placebo. For both of these endpoints, the differences between
FIRAZYR and placebo were statistically significant (p<0.001). The median
times to onset of symptom relief for patients treated with icatibant in the
FAST-1 and FAST-2 studies were consistent with the results in the FAST-3

A Phase IIIb Evaluation of the Safety of Self-Administration with
Icatibant (EASSI) study showed that self-administration of FIRAZYR for acute
attacks of HAE was generally well-tolerated. Times to symptom relief
following FIRAZYR administration were similar whether self-administered or
administered by a healthcare professional, and consistent with the Phase 3

Across the studies, almost all patients experienced injection site
reactions which were transient and generally did not require clinical
intervention. Other common adverse reactions included nausea, fever,
dizziness, headache, and rash. The safety experience reported in the
self-administration study was similar.

The active substance, icatibant, is a potent and selective bradykinin B2
receptor antagonist. It represents a novel, targeted,
subcutaneously-administered approach to the treatment of HAE attacks
designed to block the effects of bradykinin, the key mediator of edema
formation. FIRAZYR is a synthetic decapeptide .

The European Commission has approved FIRAZYR for self-administration
after training in subcutaneous injection technique by a healthcare
professional. FIRAZYR is the first and only treatment for acute Type I and
Type II HAE attacks licensed for self-administration in Europe.

FIRAZYR has an orphan drug designation status in the EU and US for
treatment of hereditary angioedema. Where commercially available, the drug
is supplied in a pre-filled 3 ml syringe. FIRAZYR can be stored at up to 25
degrees Celsius without refrigeration.

FIRAZYR is currently approved outside of the US in 37 countries
worldwide, including the countries of the European Union, for the
symptomatic treatment of acute attacks of HAE in adults (with a C1-INH
deficiency). FIRAZYR is not available in all countries and prescribing
information may differ between countries. Please consult your local
prescribing information.

Important Safety Information
Almost all subjects who were treated with FIRAZYR in clinical trials
developed reactions at the site of injection (characterized by skin
irritation, swelling, pain, itchiness, erythema, and burning sensation).
Caution should be observed when FIRAZYR is administered to patients with
acute ischemic heart disease or unstable angina pectoris and in the weeks
following a stroke.

About HAE
HAE is a rare genetic disease caused by low levels or a dysfunction of C1
esterase inhibitor (C1-INH). Reduced C1-INH activity can lead to elevated
plasma levels of bradykinin, the key mediator of HAE symptoms.

HAE is characterized by recurrent sudden attacks of edema (swelling) of
the skin (hands, arms, feet, legs, thighs, face, genitals) or the mucous
membranes (gastrointestinal tract, larynx or voicebox). The swelling can be
disfiguring and painful, especially in case of abdominal attacks. Laryngeal
attacks are potentially life-threatening due to the risk of suffocation.
Unlike angioedemas caused by allergic reactions, signs and symptoms such as
hives and itching do not occur in HAE. Signs and symptoms of HAE do not
respond to standard treatments for allergic angioedema.

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 (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:


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
           Eric Rojas (erojas@shire.com)            +1-781-482-0999
           Sarah Elton-Farr (seltonfarr@shire.com) +44-1256-894-157

           Jessica Mann (jmann@shire.com)           +44-1256-894-280
           Jessica Cotrone (jcotrone@shire.com)     +1-781-482-9538

SOURCE Shire plc

Source: newswire

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