October 31, 2016
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Mongersen trial shows positive results for Crohn's patients

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Interim results from a phase 1b trial show that 12-week treatment with mongersen resulted in endoscopic improvement and clinical response and remission in patients with active Crohn’s disease, the manufacturer announced in a press release last month.

Since then, full trial results were presented at UEG Week 2016.

Mongersen (GED-0301, Celgene) is an investigational oral antisense oligonucleotide targeting Smad7 that was shown to induce clinical remission in about 60% of patients with active Crohn’s disease in a previous phase 2 trial. It is designed to act locally and is thought to reduce inflammation-causing Smad7 levels with minimal systemic exposure, according to a press release.

William Sandborn, MD

William Sandborn

“At this early 12-week time point, we’re looking at the proportion of patients who had a 25% or greater endoscopic improvement, suggesting mucosal healing is underway in these patients,” William Sandborn, MD, professor of medicine, chief of the division of gastroenterology, and director of the Inflammatory Bowel Disease Center at University of California San Diego, said in the press release. “These data support the notion that GED-0301, a potential first-in-class oral antisense therapy, may target an underlying cause of Crohn’s disease, rather than simply improving symptoms.”

The ongoing CD-001 study is a randomized, double blind, multicenter, exploratory phase 1b trial evaluating the effects of three oral mongersen regimens on endoscopic and clinical outcomes in patients with active Crohn’s disease. Patients enrolled in this trial were more diverse than previous mongersen studies, including those with endoscopically confirmed mucosal damage, those with prior surgeries, those who were either exposed or unexposed to biologics, and those with ileitis, ileocolitis or colitis.

Investigators randomly assigned these 63 patients (mean age, 41.5 years) to receive 160 mg mongersen once daily for 4, 8 or 12 weeks. After the treatment phase, patients entered an off-treatment observation phase lasting up to 52 weeks, and an additional 24-week on-treatment extension phase is available for eligible patients.

By week 2 researchers observed clinical improvements, and clinical response and remission was maintained or increased in all dose groups through 12 weeks, with the highest rates occurring in the 12-week group (67% and 48%, respectively). In this group, the mean CDAI reduction from baseline was 133 points at week 12.

Moreover, 52 patients had evaluable endoscopies at week 12, and 37% of them had an endoscopic response, which were comparable across treatment groups. Additionally, 16 patients had greater baseline endoscopic disease activity; 63% of them had at least a 25% reduction in simple endoscopic score, and 31% had at least a 50% reduction.

There were also no new safety signals, and tolerability was comparable to that found in previous studies.

“Given the high unmet need in Crohn’s disease, we are pleased that oral GED-0301 showed both endoscopic improvements and clinically meaningful responses and remission at an early time point in this study,” Scott Smith, president of Celgene Inflammation and Immunology, said in the press release. “These data are particularly encouraging for several reasons, including the difficult-to-treat patient population evaluated in the trial.”

The study will continue until all patients complete the observation phase, according to the press release. Observation phase data are expected next year, and the phase 3 registration program is ongoing.

Reference:

Feagan BG, et al. Presented at: United European Gastroenterology Week; Oct. 15-19, 2016; Vienna.

Disclosures: Smith is employed by Celgene. Sandborn reports consulting for Celgene Cellular Therapeutics, Mesoblast, Salix, AbbVie, Catabasis, Shire, Vertex, Prometheus Laboratories, Takeda, UCB Pharma, Ardelyx, Avaxia, Ferring, Actavis, Seattle Genetics, Medimmune, Kyowa Hakko Kirin Pharmaceuticals, Actogenix, Lipid Therapeutics, Eisai, Sigmoid Biotechnologies, Teva Pharmaceuticals, Lilly, Western University (owner of Robarts Clinical Trials), Torray, Index Pharmaceuticals, Tigenix, Adherion, Ironwood Pharmaceuticals, Tillotts Pharma, Immune Pharmaceuticals, Gilead, Receptos, Janssen, Pfizer, Amgen, Genetech, Chiasma, Gilead and Cosmo.

Editor’s Note: This article was updated on Oct. 31 with additional data presented at UEG Week.