Mongersen appears to induce remission in Crohn's disease
Patients with Crohn’s disease achieved remission and clinical response in greater proportions with mongersen, a novel oral SMAD7 antisense oligonucleotide, compared with placebo, according to recent study data.
Researchers performed a phase 2, multicenter, double blind, placebo-controlled trial to assess the safety and efficacy of mongersen (Celgene) for treatment of active Crohn’s disease. From September 2011 to June 2013, patients aged 18 to 75 years (n = 166) were randomly assigned to 10 mg, 40 mg or 160 mg mongersen or placebo daily for 2 weeks. Treatment was completed by 96.4% of patients and 84-day follow-up was completed by 83.1%.
Of the patients who received 40 mg and 160 mg mongersen, respectively, 55% and 65% safely achieved clinical remission by day 15 and remained in remission for at least 2 weeks, compared with 10% who received placebo (P < .001). The difference between the placebo group and the 10-mg group (12%) was not significant. The rate of clinical response was 17% for the placebo group compared with 37% for the 10-mg group (P = .04), 58% for the 40-mg group (P < .001) and 72% for the 160-mg group (P < .001). The majority of adverse events were not related to treatment.
“In conclusion, the data from this phase 2 study provide evidence of the efficacy and adverse-effect profile of mongersen in active Crohn’s disease,” the researchers wrote. “Our results support earlier work showing that SMAD7 has a role in the inflammatory reaction of Crohn’s disease.”
Séverine Vermeire, MD, PhD, from the University Hospitals in Leuven, Belgium, wrote in an accompanying editorial, “The remission rates of between 55% and 65% are unprecedented when compared with those reported in the large pivotal induction studies of infliximab ([Remicade, Janssen Biotech] 32.5% glucocorticoid-free clinical remission at week 6 in the SONIC trial), adalimumab ([Humira, AbbVie] 36% clinical remission at week 4 in the CLASSIC-I trial), and more recently, vedolizumab ([Entyvio, Takeda]14.5% clinical remission at week 6 and 39% at week 54 in the GEMINI 2 trial), all of which also involved patients with moderate-to-severe active Crohn’s disease.” However, she said not requiring endoscopic confirmation of active disease in its inclusion criteria was a limitation of the study. “In conclusion, the impressive clinical effects of mongersen beg for follow-up studies to confirm that we have indeed entered a new phase of Crohn’s disease treatment.” – by Adam Leitenberger
Disclosure: This study was funded by Giuliani, an Italian pharmaceutical company, acting under contract to Nogra Pharma, Milan. Monteleone reports a financial relationship with Giuliani SpA. Vermeire reports financial relationships with AbbVie, Genentech/Roche, Merck Sharp & Dohme, Pfizer and Takeda. Please see the study for a list of all other authors’ relevant financial disclosures.