Shire Reports Top-Line Results on OPUS-2, a Phase 3 Study Investigating the Use
of Lifitegrast (5.0% Ophthalmic Solution) in Adults With Dry Eye Disease
December 6, 2013 -- Shire plc (LSE: SHP, NASDAQ: SHPG), the global specialty
biopharmaceutical company, today announced top-line results from OPUS-2, a
Phase 3 efficacy and safety study of 5.0% lifitegrast ophthalmic solution.
OPUS-2 compared lifitegrast to placebo administered twice daily for 84 days (12
weeks) in dry eye patients with history of active artificial tear use within 30
days prior to screening. Lifitegrast met the prespecified co-primary endpoint
for the patient-reported symptom of eye dryness (change in Eye Dryness Score
from baseline to week 12) (p-value<0.0001). Lifitegrast did not meet the
prespecified co-primary endpoint for the sign of inferior corneal staining
score (change from baseline to Week 12) using fluorescein staining compared
with placebo (p-value=0.6186).
"In this clinical trial, we note that lifitegrast showed a statistically
significant improvement in the prespecified symptoms of dry eye disease and is
the first drug to do so in a phase 3 clinical trial," said Flemming Ornskov,
M.D., Chief Executive Officer, Shire. "We will be examining the totality of the
data for lifitegrast in OPUS-2, as well as OPUS-1 and across the entire
clinical trial program. We look forward to discussing the lifitegrast program
with regulatory authorities."
The study also evaluated the safety and tolerability of lifitegrast based on
occurrence of treatment-emergent adverse events (TEAEs). 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). There were no ocular serious TEAEs
or drug-related serious TEAEs. 93.2% of patients enrolled in the study remained
for the entire duration of the 12-week clinical trial.
ABOUT THE LIFITEGRAST PHASE 3 CLINICAL DEVELOPMENT PROGRAM
OPUS-1, OPUS-2 and SONATA currently make up the phase 3 clinical development
program for lifitegrast.
OPUS-1 was a multicenter, placebo-controlled trial conducted in a controlled
adverse environment with 588 dry eye subjects to investigate the efficacy and
safety of lifitegrast (5.0% solution) versus placebo twice daily for 84 days.
* In OPUS-1, the pre-specified co-primary endpoints were: 1) mean change from
baseline to Day 84 in the inferior corneal fluorescein staining score
(i.e., "sign"); and 2) the mean change from baseline to Day 84 in the
Visual Related (VR) function subscale of the Ocular Surface Disease Index
(OSDI) (i.e., "symptom"). In this study, lifitegrast demonstrated
superiority over placebo on the sign endpoint of improvement of the
inferior corneal fluorescein staining score (P=0.0007). Ocular surface
damage, which is a hallmark of chronic inflammation from dry eye disease,
is often detected using this staining parameter. However, the co-primary
symptom endpoint, the VR function subscale of the OSDI, did not achieve
* There were no serious ocular adverse events. The most commonly reported
ocular adverse events were irritation and pain upon initial instillation,
and were generally mild in severity.
OPUS-2, initiated in December 2012, was conducted in the natural environment
and compared lifitegrast to placebo administered twice daily for 84 days (12
weeks) in dry eye patients with history of active artificial tear use within 30
days prior to screening.
OPUS-2 was a multicenter, randomized, double-masked, placebo-controlled,
parallel-arm study with a 14-day open-label placebo screening run-in period.
Patients randomized into the study were not allowed to use artificial tears
during the study. Overall, 718 patients were randomized at 31 US sites. The
study consisted of 5 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).
SONATA, which was initiated in December 2012, is a prospective, randomized,
double-masked, placebo-controlled trial in 300 dry eye subjects to evaluate the
safety of lifitegrast for 1 year. This trial is scheduled for completion in mid
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.
For further information please contact:
Eric Rojas email@example.com +1 781 482 0999
Sarah Elton-Farr firstname.lastname@example.org +44 1256 894157
Jessica Mann email@example.com +44 1256 894 280
Gwen Fisher firstname.lastname@example.org +1 484 595 9836
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,
Internal Medicine and Regenerative Medicine and we are developing treatments
for symptomatic conditions treated by specialist physicians in other targeted
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
* Shire's products may not be a commercial success;
* revenues from ADDERALL XR are subject to generic erosion;
* 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 and earnings;
* Shire relies on a single source for manufacture of certain of its products
and a disruption to the supply chain for those products may result in Shire
being unable to continue marketing or developing a product or may result in
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and is reliant upon third party contractors for certain goods and services,
and any inability of these third party manufacturers to manufacture
products, or any failure of these third party contractors to provide these
goods and services, in each case in accordance with its respective
contractual obligations, could adversely affect Shire's ability to manage
its manufacturing processes or to operate its business;
* 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
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ability to obtain, maintain, 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;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.
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-0- Dec/06/2013 07:00 GMT
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