Analysis of Phase II Data for Celgene’s Investigational Oral GED-0301 in Patients with Active Crohn’s Disease Presented at Digestive Disease Week

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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