Shire Reports Topline Results from First of Three Placebo-Controlled Phase 2
Studies of SHP625 (LUM001) in Children with Alagille Syndrome
Lexington, Mass. - April 09, 2015 - Shire plc (LSE: SHP, NASDAQ: SHPG) today
announced that the 13-week Phase 2 IMAGO trial of its investigational compound
SHP625 (LUM001) did not meet the primary or secondary endpoints in the study of
20 pediatric patients with Alagille syndrome (ALGS), a rare, life-threatening
genetic disorder that presents with chronic cholestasis (accumulation of bile
acids in the liver) and severe pruritus (itching). The primary endpoint was the
change from baseline in serum bile acid levels as compared to placebo. The
secondary endpoint of pruritus was assessed using the novel ItchRO' instrument.
Mean serum bile acid levels and pruritus at the end of the study were lower in
both SHP625 and placebo treated groups as compared to baseline. However, in a
post-hoc analysis, a positive correlation between percent changes from baseline
in serum bile acid levels and pruritis was observed in the SHP625 treated
group. The number of patients in the placebo treated group was too small to
make an accurate assessment of this relationship.
There were no treatment emergent serious adverse events in this study. As
expected, the most common adverse events were diarrhea and abdominal pain,
which were more frequent with SHP625 than with placebo.
"We have gained important insights from these first results from one of several
phase 2 studies in the SHP625 development program," said Philip J. Vickers,
Ph.D., Head of Research and Development, Shire. "We remain committed to
continuing the ongoing studies of SHP625 in ALGS and other indications."
In addition to IMAGO, two larger placebo-controlled phase 2 studies in ALGS are
in progress, one of which has pruritus as the primary endpoint. SHP625 is also
being studied in progressive familial intrahepatic cholestasis, primary biliary
cirrhosis and primary sclerosing cholangitis.
ABOUT THE IMAGO STUDY
IMAGO is a phase 2 multicenter, randomized, placebo-controlled study of
children with ALGS, 1-18 years of age, conducted in the United Kingdom.
Subjects (n=20) were randomized to receive oral, once-daily SHP625, 140 µg/kg/
day (n=6) or 280 µg/kg/day (n=8) or placebo (n=6). The primary endpoint was
change in fasting serum bile acid levels from baseline to Week 13. Serum bile
acid level reductions from baseline were -66.1 µmol/L and -42.1 µmol/L (p=0.69)
in the SHP625 and in the placebo treated groups, respectively. For the
secondary endpoint of pruritus, the change from baseline for the ItchRO(Obs)
scores was -0.61 and -0.59 (p=0.95) in the SHP625 and the placebo treated
groups, respectively. Additional secondary endpoints included change in liver
enzymes. The most common adverse events with SHP625 vs placebo were diarrhea
(64.3% vs 33.3%) and abdominal pain (42.9% vs 16.7%).
ABOUT SHP625
SHP625 is being studied in several rare cholestatic liver diseases for both
pediatric and adult populations. Preclinical models demonstrate that SHP625 is
a potent, selective minimally absorbed inhibitor of the apical sodium-dependent
bile acid transporter. It blocks bile acid reabsorption in the terminal ileum
and increases fecal bile acid excretion, thereby reducing recirculation of bile
acids to the liver.
ABOUT ALAGILLE SYNDROME
Alagille syndrome (ALGS) is a rare, life-threatening genetic disorder occurring
in approximately one in 30,000 live births that affects the liver, heart,
kidney and other systems of the body. Problems associated with the disorder
generally become evident in infancy or early childhood. A person with Alagille
syndrome has fewer than the normal number of bile ducts inside the liver. This
causes bile to build up in the liver, a condition called cholestasis, and leads
to liver damage. In addition, a buildup of bile acids in the blood also can
cause pruritus, or itching, which can be severe. There are no approved medical
therapies for ALGS, but some treatments can address its symptoms. Ten to 30
percent of people with ALGS will require a liver transplant.
For further information please contact:
Investor Relations
Sarah Elton-Farr seltonfarr@shire.com +44 1256 894157
Media
Stephanie Fagan sfagan@shire.com +1 201 572 9581
Gwen Fisher gfisher@shire.com +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 focus on providing treatments in Rare Diseases, Neuroscience,
Gastrointestinal and Internal Medicine and we are developing treatments for
symptomatic conditions treated by specialist physicians in other targeted
therapeutic areas, such as Ophthalmics.
www.shire.com
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