65 percent of patients treated with GED-0301
160 mg once daily for two weeks achieved clinical remission at both
day 15 and day 28, versus 10 percent of patients on placebo
72 and 67 percent of patients treated with 160
mg once daily were in clinical remission at day 28 and at day 84,
respectively
Overall rates of adverse events and serious
adverse events were similar across treatment groups, including
placebo
Celgene Corporation (NASDAQ:CELG) today announced that results
from a double-blind, placebo-controlled, multicenter phase II trial
of three doses of GED-0301 (mongersen) in patients with active
Crohn's disease were published in the March 19 issue of The New
England Journal of Medicine.
“GED-0301 offers a unique approach to treating Crohn’s, using
antisense technology to target a key intracellular signaling
protein thought to be involved in intestinal inflammation and the
pathogenesis of the disease,” said Professor Giovanni Monteleone,
University of Rome Tor Vergata. “This orally administered therapy
is designed to act locally with its novel mechanism of action. The
results from the phase II trial suggest that GED-0301 should be
studied further in phase III trials for Crohn’s disease.”
This phase II trial enrolled 166 adult patients with
moderate-to-severe Crohn’s disease, defined as Crohn’s Disease
Activity Index (CDAI) ranging from 220 to 400 at least one week
prior to enrollment, with documented inflammatory lesions in the
terminal ileum and/or right colon.
The newly published findings from this phase II study showed
that a significantly greater proportion of patients with active
Crohn’s disease achieved the primary endpoint of clinical remission
at both day 15 and day 28 with once daily GED-0301 40 mg (55
percent) or 160 mg (65 percent) than with GED-0301 10 mg (12
percent) or placebo (10 percent; P<0.001). Additionally, 67 (6/9
patients) percent of patients reached glucocorticoid-free remission
at day 84 with 160 mg GED-0301 once daily, versus 11 (1/9 patients)
percent with placebo (P=0.04).
For patients treated with GED-0301 160 mg once daily, 67
percent, 72 percent and 67 percent were in clinical remission (had
a CDAI score less than 150) on day 15, day 28 and day 84,
respectively, compared with 21 percent, 14 percent and 21 percent
on placebo (P<0.0001 vs. placebo, for each time point). Similar
results were seen in the GED-0301 40 mg once daily group (58
percent, 70 percent and 63 percent, respectively). For patients
treated with GED-0301 10 mg once daily, clinical remission was
achieved by 15 percent, 29 percent and 29 percent on day 15, day 28
and day 84, respectively (P=n.s. vs. placebo).
On day 28, 37 percent, 58 percent and 72 percent of patients
treated with once daily GED-0301 10 mg, 40 mg or 160 mg once daily,
respectively, achieved a clinical response (a 100-point reduction
in CDAI score; a secondary endpoint), compared with 17 percent with
placebo (P=0.04, P<0.001 and P<0.001, respectively).
The rates of patients with at least one adverse event (AE) in
the GED-0301 groups were 49 percent, 62 percent and 49 percent for
10 mg, 40 mg and 160 mg once daily, respectively, compared with 67
percent for the placebo group. The most commonly reported AEs in
the GED-0301 treatment groups were abdominal pain (10-12 percent),
Crohn’s disease worsening (10-15 percent), urinary tract infection
(5-15 percent) and C-reactive protein increase (5-9 percent). The
rates of serious adverse events in the GED-0301 dose groups were 7
percent, 2 percent and 2 percent for 10 mg, 40 mg and 160 mg once
daily, respectively, compared with 2 percent for the placebo
group.
“A significant number of Crohn’s disease patients don’t reach
remission with current therapies and are looking for additional
options,” said Scott Smith, President of Celgene Inflammation and
Immunology. “GED-0301 offers a completely different mechanism of
action that has the potential to transform the Crohn’s treatment
landscape. We are encouraged by the phase II data and are committed
to bringing innovative medicine to patients with Crohn’s disease,
starting with advancing the phase III trial for GED-0301.”
About the Study
This phase II trial enrolled 166 adult patients with
moderate-to-severe Crohn’s disease with documented inflammatory
lesions in the terminal ileum and/or right colon. Patients with
known lesions in the stomach, proximal small intestine, transverse
colon, and/or left colon, strictures, fistulae, perianal disease,
extraintestinal manifestations, active or recent infections or a
history of malignancy were excluded.
Patients were randomly assigned to receive treatment for two
weeks with one of three daily doses of GED-0301 (10 mg, 40 mg or
160 mg tablets, once daily) or placebo and then evaluated for
responses at days 15, 28 and 84. The primary efficacy endpoint of
the study was the percentage of patients with clinical remission,
defined as a CDAI score below 150 at day 15, which was maintained
at day 28. The secondary endpoints included clinical response
defined as a reduction of CDAI score of 100 points or 70 points at
day 15 and day 28.
Patients could continue receiving stable doses of oral
prednisolone (≤40 mg/day), budesonide (≤9 mg/day), or mesalamine
during the 2-week treatment and/or a stable dose of
immunomodulators (e.g., azathioprine, mercaptopurine, methotrexate)
if therapy was initiated ≥6 months before treatment. Antibiotics,
steroids, immunosuppressive drugs and biologics could not be
initiated prior to study entry and during the 2-week treatment.
Patients received no treatment with anti-TNF-α antibodies or other
biologics within 90 days, or antibiotics within 3 weeks of the date
of their initiation into the trial.
About GED-0301
The investigational oral antisense therapy GED-0301 is an
oligonucleotide that targets the messenger RNA (mRNA) for Smad7,
thereby reducing Smad7 protein levels. In patients with Crohn’s
disease, abnormally high levels of Smad7 interfere with TGF-β1
anti-inflammatory pathways in the gut, leading to increased
inflammation. GED-0301 is designed to act locally to reduce Smad7
levels with negligible systemic exposure.
About Crohn’s Disease
Crohn’s disease is an immune-mediated, chronic inflammatory
condition of the gastrointestinal tract. Estimated to affect as
many as three out of every 1,000 people in Europe and North
America, the disease is becoming more common for all ethnic groups.
Symptoms of Crohn’s disease — including abdominal pain, diarrhea,
fatigue, fever, weight loss and malnutrition — most commonly begin
to appear between the ages of 13 and 30, although the disease can
strike at any age. The disease may affect any part of the GI tract,
from the mouth to the anus, but most commonly affects the end of
the small bowel (the ileum) and the beginning of the colon. The
exact cause of Crohn’s disease is unknown, and there is no cure.
People with Crohn’s disease have a slightly reduced life
expectancy.
About Celgene
Celgene Corporation, headquartered in Summit, New Jersey, is an
integrated global pharmaceutical company engaged primarily in the
discovery, development and commercialization of innovative
therapies for the treatment of cancer and inflammatory diseases
through gene and protein regulation. For more information, please
visit www.celgene.com. Follow Celgene on Twitter @Celgene, and on
Pinterest and LinkedIn.
Forward-Looking Statements
This press release contains forward-looking statements, which
are generally statements that are not historical facts.
Forward-looking statements can be identified by the words
“expects,” “anticipates,” “believes,” “intends,” “estimates,”
“plans,” “will,” “outlook” and similar expressions. Forward-looking
statements are based on management’s current plans, estimates,
assumptions and projections, and speak only as of the date they are
made. We undertake no obligation to update any forward-looking
statement in light of new information or future events, except as
otherwise required by law. Forward-looking statements involve
inherent risks and uncertainties, most of which are difficult to
predict and are generally beyond our control. Actual results or
outcomes may differ materially from those implied by the
forward-looking statements as a result of the impact of a number of
factors, many of which are discussed in more detail in our Annual
Report on Form 10-K and other reports filed with the Securities and
Exchange Commission.
# # #
For inquiries, please contact:Celgene
CorporationInvestors:Patrick E. Flanigan III, 908-673-9969Vice
President, Investor RelationsorMedia:Catherine Cantone,
732-564-3592Director, Corporate Communications
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