Results from Phase 2 Studies of Oral Ozanimod in Crohn's Disease and Ulcerative Colitis to Be …

SUMMIT, N.J.–()–Celgene Corporation (NASDAQ:CELG) today announced that phase 2 data of
investigational compound ozanimod in Crohn’s disease and ulcerative
colitis will be presented at the World Congress of Gastroenterology at
ACG2017 (WCOG at ACG2017) in Orlando. The studies include new data from
the STEPSTONE study in patients with moderately to severely active
Crohn’s disease (CD) and long-term data from the open-label extension of
the TOUCHSTONE study in patients with moderately to severely active
ulcerative colitis (UC). Ozanimod is an investigational, selective
sphingosine 1-phosphate (S1P) 1 and 5 receptor modulator.

“The new STEPSTONE findings further validate our hypothesis of ozanimod
in Crohn’s disease and the latest data from the TOUCHSTONE study
continue to support the potential of ozanimod to provide continued
efficacy in ulcerative colitis at 92 weeks,” said Terrie Curran,
President, Celgene Inflammation and Immunology. “The results in both
studies are highly encouraging as we execute pivotal studies of ozanimod
in Crohn’s disease and ulcerative colitis in hopes of advancing oral
treatment options for these patients.”

The STEPSTONE data presented at WCOG at ACG2017 will include the first
12-week data from the phase 2, open-label study. STEPSTONE evaluated
endoscopic improvement and clinical outcomes following treatment with
ozanimod 1.0 mg daily for 12 weeks in 69 patients with a mean age of
37.7 years with moderately to severely active CD. Patients with
available data at baseline and week 12 were included in the analyses of
the simple endoscopic score for Crohn’s disease (SES-CD) matched
intestinal segments (n=60) and the analysis of Crohn’s disease activity
index (CDAI) (n=59).

SES-CD score reductions from baseline of at least 50 percent and 25
percent were seen in 27 percent and 43 percent of patients,
respectively. Patients who had shorter disease duration (disease
duration ≤5 years) had a greater endoscopic response: 50 percent and 25
percent reductions were seen in 36 percent and 50 percent of patients,
respectively. Patients who had lower baseline endoscopic disease
activity (SES-CD ≤12) also had a greater endoscopic response: 50 percent
and 25 percent reductions were seen in 30 percent and 49 percent of
patients, respectively.

Reductions in mean CDAI scores from baseline were seen at week 4 (first
post-baseline assessment), with further reductions through week 12. At
week 12, a CDAI response (CDAI decrease ≥100) was observed in 66 percent
of patients, and CDAI remission (CDAI <150) was observed in 46 percent
of patients. The mean CDAI reduction at week 12 was 130 points.

The most frequently reported adverse events (AEs) and serious AEs in
patients appeared to be related to underlying CD. The most common AEs
(≥5 percent) were CD flare, abdominal pain, nausea, lymphopenia,
arthralgia, vomiting, increased gamma-glutamyl transpeptidase (GGT),
urinary tract infection, paresthesia, anal abscess and increased alanine
aminotransferase (ALT). The most common SAEs in two or more patients
were CD flare, fistulizing disease, intestinal obstruction and abdominal

“Improvements in endoscopy are thought to correlate with long-term
benefits for patients with Crohn’s disease, a chronic condition in which
patients are regularly seeking out additional options to manage their
disease,” said Brian G. Feagan, M.D., Robarts Clinical Trials and the
University of Western Ontario in Canada. “The endoscopic, clinical
improvement and the safety profile of ozanimod reported in the STEPSTONE
study are encouraging and support its further development as a potential
oral option for patients with Crohn’s disease.”

A separate presentation at WCOG at ACG2017 will report 92-week data on
subjects who participated in the TOUCHSTONE open-label extension.
TOUCHSTONE evaluated the efficacy and safety of 0.5 mg and 1.0 mg doses
of ozanimod compared with placebo after eight weeks of treatment
(induction phase) in 197 patients with moderate to severe UC. The
primary endpoint was the proportion of patients in remission at week 8.
Patients who achieved a clinical response at week 8 continued with their
original treatment through week 32 in a maintenance phase. Previously
reported results from TOUCHSTONE demonstrated statistically significant
improvements in both the primary and secondary endpoints in patients who
received 1.0 mg dose of ozanimod versus placebo.

TOUCHSTONE participants in all three treatment arms entered the ongoing
open-label extension if they did not respond to treatment after the
induction phase, relapsed during the maintenance phase or completed the
maintenance phase (170 of the 197 patients). The objective of the
extension phase was to evaluate the long-term efficacy and safety of
daily ozanimod 1.0 mg. Efficacy data are reported as observed through
week 92 and safety data includes all events through the data cut-off of
March 2017.

At week 92, of the 100 patients who underwent efficacy evaluations, 91
percent had little or no active disease based on the physician global
assessment (PGA 0 or 1), 97 percent had little or no blood in their
stools (rectal bleeding subscore [RBS] 0 or 1) and 86 percent had no
blood in the stools (RBS 0).

The safety profile at week 92 was similar to that reported in the
placebo-controlled portion of the study. The most common AEs were UC
flare, anemia, upper respiratory tract infection and back pain. The only
SAEs in two or more patients were anemia and UC flare.

“People with ulcerative colitis need additional treatment options that
can provide long-term benefit,” said William Sandborn, M.D., Professor
of Medicine and Chief, Division of Gastroenterology and
Director, University of California San Diego Inflammatory Bowel Disease
Center. “These results further support the potential of longer-term
treatment with ozanimod.”


STEPSTONE is a phase 2, open-label study in patients with moderately to
severely active Crohn’s disease (CD). Data from the first 12 weeks
examined endoscopic and clinical outcomes following treatment with
ozanimod 1.0 mg daily for 12 weeks. Active Crohn’s disease was defined
as CDAI score 220-450 and total SES-CD of 6 or greater (or in isolated
ileum disease SES-CD of 4 or greater). For the 69 enrolled patients,
baseline mean age was 37.7 years, mean SES-CD was 13.3 and mean CDAI was
320. Mean CD duration was 10 years, with 54 percent of patients having
had prior exposure to biologic therapy. All endoscopic assessments were
read in a blinded manner by an imaging core lab. Daily electronic diary
records were used to collect CD symptoms (including abdominal pain and
soft/loose stool frequency). SES-CD was evaluated at baseline and week
12, and CDAI was assessed at baseline and weeks 4, 8 and 12.


TOUCHSTONE is a phase 2, randomized, double-blind, placebo-controlled
trial comparing the efficacy and safety of ozanimod (also known as
RPC1063) with placebo in patients with moderately to severely active
ulcerative colitis. A total of 197 patients were randomized and treated
once daily with 1.0 mg ozanimod (n=67), 0.5 mg ozanimod (n=65) or
placebo (n=65) for eight weeks (the induction phase). The primary
endpoint was the proportion of patients in remission (Mayo score ≤2, no
subscore > 1) at week 8. Secondary endpoints were the proportion of
patients achieving clinical response (reduction in Mayo score of ≥3 and
≥30 percent with a decrease in the rectal bleeding score of ≥1 or a
rectal bleeding score ≤1), proportion of patients with mucosal
improvement (endoscopy score ≤1) and the change in Mayo score. Safety
assessments included ECG testing, pulmonary function testing, optical
coherence tomography and adverse events.

For the maintenance phase, patients who achieved a clinical response at
week 8 continued with their original treatment through week 32. In the
open-label extension phase, all patients (n=170) were treated with
ozanimod 1.0 mg. The week 44 visit was completed by 131 patients.

About Ozanimod

Ozanimod is a novel, oral, selective, sphingosine 1-phosphate 1 and 5
receptor modulator in development for immune-inflammatory indications
including relapsing multiple sclerosis, ulcerative colitis and Crohn’s
disease. Selective binding with S1PR1 receptors is believed to inhibit a
specific subset of activated lymphocytes from migrating to sites of
inflammation. The result is a reduction of circulating lymphocyte count
that leads to anti-inflammatory activity. Importantly, immune
surveillance is maintained.

Ozanimod is an investigational compound that is not approved for any use
in any country.

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

About Ulcerative Colitis

Ulcerative colitis is a chronic, relapsing condition triggered by an
abnormal, prolonged immune response that creates long-lasting
inflammation and ulcers (sores) in the mucosa (lining) of the large
intestine (colon). Symptoms usually develop over time, rather than
suddenly. The disease can be debilitating and can sometimes lead to
life-threatening complications. Ulcerative colitis is the most common
form of inflammatory bowel disease worldwide. About one in every 198
people in Europe, and one in every 402 people in North America, have
ulcerative colitis. In 2004, 2.1 million prescriptions were written to
treat ulcerative colitis, and 716,000 ambulatory care visits were
related to the disease. In 2010, there were 107,000 hospitalizations due
to ulcerative colitis.

About Celgene

Celgene Corporation, headquartered in Summit, New Jersey, is an
integrated global biopharmaceutical company engaged primarily in the
discovery, development and commercialization of innovative therapies for
the treatment of cancer and inflammatory diseases through
next‐generation solutions in protein homeostasis, immuno‐oncology,
epigenetics, immunology and neuro‐inflammation. For more information,
please visit
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