SUMMIT, N.J.—Last month, Celgene Corp. released interim top-line study data regarding the effects of oral GED-0301 (mongersen) on both endoscopic and clinical outcomes in patients with active Crohn’s disease. The ongoing, randomized, double-blind, multicenter, exploratory Phase 1b trial, CD-001, is currently evaluating the use of GED-0301 in a 12-week course of treatment followed by 52 weeks of off-treatment observation. Some eligible patients will also receive a 24-week on-treatment extension phase.
The trial, which enrolled 63 candidates in various countries, includes patients with endoscopically confirmed mucosal damage at entry and those who had previous surgeries, reportedly making it one of the most diverse studies of its kind to date. Designed to explore how GED-0301 acts in a difficult-to-treat, moderate-to-severe patient population, the study also included both biologic-exposed and biologic-naïve patients, as well as patients with a diagnosis of ileitis, ileocolitis or colitis.
“At this early 12-week timepoint, we’re looking at the proportion of patients who had a 25-percent or greater endoscopic improvement, suggesting mucosal healing is underway in these patients,” said Dr. William Sandborn, a professor of medicine and chief of Division of Gastroenterology and director of the University of California, San Diego Inflammatory Bowel Disease Center. “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.”
Estimated to affect as many as three out of every 1,000 people in Europe and North America, Crohn’s disease is an immune-mediated, chronic inflammatory condition of the gastrointestinal tract, and it is becoming more common for all ethnic groups. Symptoms include abdominal pain, diarrhea, fatigue, fever, weight loss and malnutrition, and generally appear between the ages of 13 and 30, although the disease can strike at any age. The cause of Crohn’s disease is unknown, and there is no cure.
“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 timepoint in this study,” said Scott Smith, president of Celgene Inflammation and Immunology. “These data are particularly encouraging for several reasons, including the difficult-to-treat patient population evaluated in the trial.”
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. It has not yet been approved for use in any country.
Top-line data from CD-001 show that in a proportion of patients treated with oral GED-0301, there was endoscopic improvement and clinical response and remission across all treatment groups at week 12, and that thus far, safety and tolerability results have been consistent with past studies. The study will continue until all patients have completed the observation phase— estimated for some time in 2017—but full results from the 12-week course have been submitted for review at a scientific conference later in the year, and registration for Phase 3 is underway.
Celgene also recently reported strong second quarter earnings for four of its current products—Revlimid, Pomalyst/Imnovi, Abraxane and Otezla—making what CEO Mark J. Alles called “outstanding” progress.
“We believe Celgene’s success with Otezla also bodes well for a launch of GED-0301 (should it be approved), whose oral formulation will likely be a strong value driver in and of itself, as opposed to on efficacy alone,” stated Canaccord Genuity healthcare analyst Dr. John Newman. “Such an oral therapy would not only be of benefit to patients looking to avoid systemic, infused biologics due to cost and side effects, but would also allow Celgene some flexibility with its pricing, a critical advantage in today’s reimbursement environment.”
In other news, it was also recently reported that Celgene expects to submit an New Drug Application to the U.S. Food and Drug Administration for AG-221, a first-in-class, oral, selective, potent inhibitor of mutant IDH2 in relapsed and/or refractory AML based on data from another study related to advanced hematologic malignancies with an IDH2 mutation. The submission is expected by the end of the year.