Patients with more severe Crohn’s disease or
longer disease duration treated with GED-0301 160 mg experienced
clinical remission and response rates greater than placebo
Celgene Corporation (NASDAQ: CELG) today announced that a
post-hoc subgroup analysis of a double-blind, placebo-controlled,
randomized, multicenter phase II trial of GED-0301 (mongersen) in
patients with active Crohn's disease was presented at Digestive
Disease Week (DDW) in Washington, D.C.
“For patients with Crohn’s, disease severity and duration can
influence the therapeutic effect of certain medicines,” said
Professor Giovanni Monteleone, University of Rome Tor Vergata.
“This subgroup analysis of data from the phase II study explored
the effects of these factors on clinical response and clinical
remission rates with GED-0301 — being investigated as an orally
administered antisense therapy with a novel mechanism of action
designed to act locally.”
The primary findings of the phase II trial, which enrolled 166
adult patients with active Crohn’s disease, defined as Crohn’s
Disease Activity Index (CDAI) scores >220 to ≤400, were
published in the March 19, 2015 issue of The New England Journal of
Medicine. Patients in the trial were treated for two weeks with
either placebo or one of three doses of GED-0301 (10 mg, 40 mg or
160 mg tablets, once daily) and then followed for an additional 10
weeks. The presentation at DDW retrospectively examined certain
subgroups of patients in the trial.
In the subgroup analysis, patients were grouped by disease
duration (<5 years vs. ≥5 years), baseline CDAI score (<260
vs. ≥260) and baseline levels of the C-reactive protein (CRP)
inflammatory marker (<3 mg/L vs. ≥3 mg/L). Patients in these
subgroups were then analyzed for clinical remission (a CDAI score
<150) and clinical response (CDAI score reduction ≥100 points
from baseline) at weeks 2 and 4. Clinical remission rates for
patients treated with GED-0301 160 mg were similar regardless of
disease duration or baseline CDAI or CRP levels and were higher
than those for patients on placebo (remission rates ranged from
62.5 percent to 75 percent for GED-0301 160 mg vs. 5 percent to 24
percent for placebo). These findings provide a rationale for
continued evaluation of the 160 mg dose in the phase III
program.
For patients with a disease duration of at least five years
(mean of 15.4 years), 62.5 percent (15/24) of those treated with
GED-0301 160 mg were in clinical remission at week 2, compared with
15.4 percent (4/26) of those treated with placebo. Similar results
were observed at week 4 (66.7 percent [16/24] vs. 15.4 percent
[4/26], respectively). Clinical response rate was 70.8 percent
(17/24) with GED-0301 160 mg, compared with 19.2 percent (5/26)
with placebo, at week 2 and 79.2 percent (19/24) versus 26.9
percent (7/26), respectively, at week 4.
For patients with baseline CDAI of at least 260 (median of 303),
62.5 percent (10/16) of those treated with GED-0301 160 mg were in
clinical remission at week 2, compared with 13.6 percent (3/22) for
placebo and 75.0 percent (12/16) versus 4.5 percent (1/22),
respectively, at week 4. Clinical response rate was 87.5 percent
(14/16) with GED-0301 160 mg versus 22.7 percent (5/22) for placebo
at week 2 and 87.5 percent (14/16) versus 22.7 percent (5/22),
respectively, at week 4.
Similar results were observed for patients with baseline CRP of
at least 3 mg/L (about 60 percent of patients in the trial). At
week 2, 71.4 percent (20/28) of patients in the GED-0301 160 mg
group achieved clinical remission compared with 24.0 percent (6/25)
in the placebo group. At week 4, similar results were observed
(75.0 percent [21/28] vs. 12.0 percent [3/25]). In the GED-0301 160
mg group, 60.7 percent (17/28) and 64.3 percent (18/28) had a
clinical response at weeks 2 and 4, respectively, compared with
32.0 percent (8/25) and 24.0 percent (6/25) in the placebo
group.
The rates of patients with at least one adverse event (AE) were
49 percent, 62 percent and 49 percent for the GED-0301 10 mg, 40 mg
and 160 mg doses, respectively, and 67 percent for placebo. 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 CRP increase
(5-9 percent). The rates of serious AEs in the GED-0301 groups were
7 percent, 2 percent and 2 percent for 10 mg, 40 mg and 160 mg
dose, respectively, compared with 2 percent for placebo.
“The analysis presented at DDW suggests that patients with more
severe Crohn’s disease or a longer duration of disease were able to
achieve clinical response or clinical remission with the 160 mg
dose of GED-0301,” said Scott Smith, President of Celgene
Inflammation and Immunology. “Patients with moderate to severe
Crohn’s disease are in need of new treatment options. Based on
these findings, and as part of our commitment to bringing
innovative medicines to this patient community, we look forward to
continued study of this potentially transformative therapy in phase
III trials.”
DDW Abstract Number: 826
About the Trial
The 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 is designed to target 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 and is thought 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 Social Media: @Celgene,
Pinterest, LinkedIn and YouTube.
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Celgene CorporationInvestors:Patrick E. Flanigan III,
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Cantone, 732-564-3592Director, Corporate Communications
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