Experimental Drug Shows Strong Response in Crohn's Disease Patients

A phase 1b study produced positive results at 12 weeks of treatment with investigational oral GED-0301 (mongersen) in patients with active Crohn’s disease.

GED-0301 is an oligonucleotide designed to target mRNA for Smad7, in order to reduce Smad7 protein levels. The randomized, double-blind, multicenter, exploratory CD-001 phase 1b study evaluated the effects of oral GED-0301 on endoscopic and clinical outcomes in patients with active Crohn’s disease.

For the study, researchers enrolled 63 patients randomized in a 1:1:1 ratio to receive either 160-mg GED-0301 once daily for 12-weeks; 160-mg GED-0301 once daily for 8-weeks followed by 4 weeks of placebo; or 160-mg GED-0301 once daily for 4 weeks followed by 8 weeks of placebo. This treatment phase was followed by an off-treatment observation phase for up to 52 weeks.

Additionally, eligible patients can enter an extension phase for an additional 100 weeks.

The results of the study revealed that by week 2, clinical improvements were observed. Clinical response (CDAI decrease ≥100) and remission (CDAI < 150) rates at week 12 were found to be highest in the 12-week treatment group at 67 and 48%, respectively. In the 12-week treatment arm, the mean CDAI reduction from baseline at week 12 was 133 points.

Patients with evaluable endoscopies at week 12 (n=52), 37% had an endoscopic response (≥25 percent reduction in SES-CD score from baseline) with no meaningful difference across the treatment arms. Of the patients with greater endoscopic disease activity at baseline (SES-CD score of > 12; n=16), 63% exhibited a reduction of ≥25% in SES-CD score, while 31% had a reduction of ≥50%.

“We are encouraged that oral GED-0301 showed meaningful endoscopic improvement and clinical remission at an early time point in this study,” said Scott Smith, president of Celgene Inflammation and Immunology. “The fact that this study included nearly 50% biologic-experienced patients further reflects the potential of GED-0301 as a novel approach for patients with Crohn’s disease searching for alternatives.”

Adverse events (AEs) and serious AEs were found to be low and similar across the treatment arms. Additionally, there were no new safety signals for 160 mg of GED-0301 daily that were reported in the study.

“A significant number of Crohn’s disease patients don’t reach remission with current therapies or will suffer relapses over time and are in need of new treatment options,” said Brian Feagan, MD, director of Robarts Clinical Trials at Robarts Research Institute. “Based on these findings, oral GED-0301 has the potential to provide a new, oral option with a novel mechanism of action designed to act locally.”