Shire Announces Updates from Phase 3 Clinical Program for Lifitegrast in Adults With Dry Eye Disease

   Shire Announces Updates from Phase 3 Clinical Program for Lifitegrast in
                         Adults With Dry Eye Disease

  PR Newswire

  LEXINGTON, Massachusetts, April 30, 2014

LEXINGTON, Massachusetts, April 30, 2014 /PRNewswire/ --

  *OPUS-2 , a Phase 3 placebo-controlled study of lifitegrast 5.0%; results
    presented at the American Society of Cataract and Refractive Surgery
    (ASCRS) annual meeting in Boston
  *SONATA , a Phase 3 placebo-controlled, long-term (one-year) safety study
    of lifitegrast 5.0%; top-line results announced

Shire plc (LSE: SHP, NASDAQ: SHPG), the global specialty biopharmaceutical
company, presented study results from its pivotal Phase 3 OPUS -2 study
investigating lifitegrast (5.0% ophthalmic solution) in adults with dry eye
disease at the 2014 American Society of Cataract and Refractive Surgery
(ASCRS) annual meeting in Boston earlier this week. In addition, today the
company announces top-line results from the prospective, randomized,
double-masked, placebo-controlled, long-term (one-year) Phase 3 SONATA safety
study.

"These clinical trials are part of a large Phase 3 clinical program with more
than 1,600 patients," said Phil Vickers, Ph.D., Head of Research & Development
at Shire. "We look forward to meeting with the FDA to discuss the totality of
data for lifitegrast, which will help us determine our path forward."

OPUS-2 study results on both co-primary endpoints and secondary assessments
were presented at ASCRS earlier this week. Lifitegrast met one of the
co-primary endpoints for the patient-reported symptom of improvement in dry
eye compared with placebo (P<0.0001), but did not meet the second co-primary
endpoint of the sign of inferior corneal staining (P=0.6186). The secondary
endpoints were only descriptive in nature and were consistent with improvement
in symptoms and lack of improvement in signs.

There were no ocular serious treatment-emergent adverse events (TEAEs) or
drug-related serious TEAEs reported. The most commonly reported TEAEs
associated with lifitegrast were dysgeusia (altered sense of taste) (16.2% vs.
0.3% for placebo), instillation site irritation (7.8% vs. 1.4% for placebo),
instillation site reaction (7.0% vs. 1.1% for placebo), and visual acuity
reduced (5.0% vs. 6.4% for placebo).

"Symptoms of dry eye are certainly the most common complaints that I hear from
patients in my practice," said Joseph Tauber, M.D., of the Tauber Eye Center,
Kansas City, Mo., who also presented the OPUS-2 study results at ASCRS.
"Patients come in seeking relief from their chronic and sometimes debilitating
symptoms. It's encouraging that potential new treatment options are being
developed for dry eye disease, which affects millions of people in the U.S."

SONATA Top-Line Results 

Top-line results from the prospective, randomized, double-masked,
placebo-controlled SONATA trial indicated no ocular or drug-related serious
adverse events. Discontinuations over the course of the study were 21.1%
(23.1% for lifitegrast vs. 17.1% for placebo). At Day 360, analysis of the
primary endpoints of ocular and non-ocular adverse events (AEs) showed that
ocular AEs occurring in ≥5% of subjects included installation site irritation
(15% vs. 4.5% for placebo), installation site reaction (13.2% vs. 1.8% for
placebo), visual acuity reduced (11.4% vs. 6.3% for placebo), and dry eye
(1.8% vs. 5.4% for placebo). The most commonly reported non-ocular AE
associated with lifitegrast was dysgeusia (altered sense of taste) (16.4% vs.
1.8% for placebo). Additional data and analyses will be submitted for
presentation at upcoming medical meetings.

ABOUT OPUS-2 

OPUS-2 was a multicenter, randomized, double-masked, placebo-controlled,
parallel-arm study comparing lifitegrast to placebo administered twice-daily
for 84 days (12 weeks) in dry eye patients with a history of active artificial
tear use within 30 days prior to screening. In addition to certain
medications, key study exclusions included any ocular condition that, in the
opinion of the investigator, could affect study parameters. A 14-day
open-label placebo screening run-in period preceded randomization. Patients
had to have an inferior corneal staining score of greater than or equal to 0.5
point in at least one eye with a Schirmer Tear Test score of greater than or
equal to 1 and less than or equal to 10 mm in the same eye at Visit 1 (Day
-14, Week -2) and replicate these findings in the same eye at Visit 2 (Day 0,
Week 0) in order to be eligible for the study. Patients randomized into the
study were not allowed to use artificial tears during the study. Overall, 718
patients were randomized at 31 U.S. sites. The study consisted of five visits
over 98 days: screening visits Day -14 (Visit 1) to Day 0 (Visit 2), and
treatment visits at Day 0 (Visit 2), Day 14 (Visit 3), Day 42 (Visit 4), and
Day 84 (Visit 5).

ABOUT SONATA 

SONATA was a Phase 3, multicenter, randomized, double-masked,
placebo-controlled study evaluating the safety of 5.0% lifitegrast compared to
placebo administered twice-daily for 360 days (~ one year) in dry eye
patients. In addition to certain medications, key study exclusions included
any ocular condition that, in the opinion of the investigator, could affect
study parameters. Patients had to have a visual analogue scale score greater
than or equal to 40% in either symptom of eye dryness or discomfort, a corneal
staining score of greater than or equal to 2.0 point in at least one region in
either eye, and a Schirmer Tear Test score of greater than or equal to 1 and
less than or equal to 10 mm in either eye at Visit 1 (Day -7). Confirmatory
screening and baseline assessment occurred at Visit 2 (Day 0). Patients
randomized into the study were not allowed to use contact lenses, or any
topical ophthalmic treatments including artificial tears, steroid drops,
antihistamine drops or mast cell stabilizer drops between Visits 1 and 3 (Day
14). Following completion of Visit 3 assessments, subjects were allowed
elective use of contact lenses (daily disposable lenses only), and/or
artificial tears (up to four times a day as needed) and/or topical ophthalmic
steroids (loteprednol only), antihistamines or mast cell stabilizers. Overall,
332 patients were randomized (2:1, 5.0% lifitegrast: placebo) at 22 U.S.
sites. The study consisted of seven visits over 367 days: screening visits Day
-7 (Visit 1) to Day 0 (Visit 2), and treatment visits at Day 0 (Visit 2), Day
14 (Visit 3), Day 90 (Visit 4), Day 180 (Visit 5), Day 270 (Visit 6), and Day
360 (Visit 7).

ABOUT LIFITEGRAST 

Lifitegrast, a small-molecule integrin antagonist, was designed in order to
treat dry eye disease, and is a preservative-free topical eye solution.
Lifitegrast is believed to work by reducing inflammation through inhibition of
lymphocyte function-associated antigen 1 (LFA-1) and preventing its binding to
intercellular adhesion molecule-1 (ICAM-1) that influences T-cell activation
and cytokine (protein) release. The interaction between these two proteins
plays a key role in the chronic inflammation associated with dry eye. T-cells
are important components of the immune system that help control the body's
response to a foreign or harmful substance or stimuli.

ABOUT DRY EYE DISEASE 

As defined by the International Dry Eye Workshop in 2007, dry eye is a
multifactorial disease of the tears and ocular surface that results in
symptoms of discomfort, visual disturbance, and tear film instability with
potential damage to the ocular surface. It is accompanied by increased
osmolarity of the tear film and inflammation of the ocular surface.

NOTES TO EDITORS 

Shire enables people with life-altering conditions to lead better lives.

Our strategy is to focus on developing and marketing innovative specialty
medicines to meet significant unmet patient needs.

We provide treatments in Neuroscience, Rare Diseases, Gastrointestinal and
Internal Medicine and we are developing treatments for symptomatic conditions
treated by specialist physicians in other targeted therapeutic areas.

http://www.shire.com

FORWARD-LOOKING STATEMENTS - "SAFE HARBOR" STATEMENT UNDER THE PRIVATE
SECURITIES LITIGATION REFORM ACT OF 1995 

Statements included in this announcement that are not historical facts are
forward-looking statements. 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, Shire's results could be materially
adversely affected. The risks and uncertainties include, but are not limited
to, that:

  *Shire's products may not be a commercial success;
  *revenues from ADDERALL XR are subject to generic erosion and revenues from
    INTUNIV will become subject to generic competition starting in December
    2014;
  *the failure to obtain and maintain reimbursement, or an adequate level of
    reimbursement, by third-party payors in a timely manner for Shire's
    products may impact future revenues, financial condition and results of
    operations;
  *Shire conducts its own manufacturing operations for certain of its Rare
    Diseases products and is reliant on third party contractors to manufacture
    other products and to provide goods and services. Some of Shire's products
    or ingredients are only available from a single approved source for
    manufacture. Any disruption to the supply chain for any of Shire's
    products may result in Shire being unable to continue marketing or
    developing a product or may result in Shire being unable to do so on a
    commercially viable basis for some period of time.
  *the development, approval and manufacturing of Shire's products is subject
    to extensive oversight by various regulatory agencies and regulatory
    approvals or interventions associated with changes to manufacturing sites,
    ingredients or manufacturing processes could lead to significant delays,
    increase in operating costs, lost product sales, an interruption of
    research activities or the delay of new product launches;
  *the actions of certain customers could affect Shire's ability to sell or
    market products profitably. Fluctuations in buying or distribution
    patterns by such customers can adversely impact Shire's revenues,
    financial conditions or results of operations;
  *investigations or enforcement action by regulatory authorities or law
    enforcement agencies relating to Shire's activities in the highly
    regulated markets in which it operates may result in the distraction of
    senior management, significant legal costs and the payment of substantial
    compensation or fines;
  *adverse outcomes in legal matters and other disputes, including Shire's
    ability to enforce and defend patents and other intellectual property
    rights required for its business, could have a material adverse effect on
    Shire's revenues, financial condition or results of operations;
  *Shire faces intense competition for highly qualified personnel from other
    companies, academic institutions, government entities and other
    organizations. Shire is undergoing a corporate reorganization and the
    consequent uncertainty could adversely impact Shire's ability to attract
    and/or retain the highly skilled personnel needed for Shire to meet its
    strategic objectives;
  *failure to achieve Shire's strategic objectives with respect to the
    acquisition of ViroPharma Incorporated may adversely affect Shire's
    financial condition and results of operations;

and other risks and uncertainties detailed from time to time in Shire's
filings with the U.S. Securities and Exchange Commission, including its most
recent Annual Report on Form 10-K.

For further information please contact: 

Investor Relations 

Jeff Poulton jpoulton@shire.com +1-781-482-0945

Eric Rojas erojas@shire.com +1-781-482-0999

Sarah Elton-Farr seltonfarr@shire.com +44-1256-894157

Media

Jessica Mann jmann@shire.com +44-1256-894-280

Gwen Fisher gfisher@shire.com +1-484-595-9836


 
Press spacebar to pause and continue. Press esc to stop.