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
SUMMIT, N.J.--(Business Wire/Korea Newswire) May 20, 2015 -- 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.”