Celgene Corporation recently presented data regarding studies of its investigational oral antisense therapy called GED-0301 (mongersen) for the treatment of active Crohn’s disease at the Digestive Disease Week (DDW), which took place in Washington, D.C. The company conducted a double-blind, placebo-controlled, randomized, multicenter phase II trial and presented its post-hoc subgroup analysis.
The clinical trial was designed to evaluate the therapy, which is an oligonucleotide expected to target the messenger RNA (mRNA) for Smad7 and, consequently, decrease the levels of Smad7 protein, in 166 adults who suffer from moderate-to-severe Crohn’s disease, as well as inflammatory lesions in the terminal ileum and/or right colon. The high levels of Smad7 cause abnormal function of the TGF-β1 anti-inflammatory pathways in the gut, worsening inflammation.
“For patients with Crohn’s, disease severity and duration can influence the therapeutic effect of certain medicines,” explained in a press release professor Giovanni Monteleone from the 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.”
Celgene researchers focused on the Crohn’s Disease Activity Index (CDAI) scores >220 to ≤400 as primary findings of the phase II study, results that were published last March in The New England Journal of Medicine. Crohn’s disease patients received treatment with placebo or three doses of GED-0301 for two weeks, and were followed during 10 weeks after that. At the DDW, the investigators presented data on patients’ subgroups enrolled in the study.
“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 the president of Celgene Inflammation and Immunology, Scott Smith. “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.”
The patients were divided in groups according to disease duration, baseline CDAI score and baseline levels of C-reactive protein inflammatory marker, to conduct the subgroup analysis, which included evaluation of clinical remission and response at the second and fourth weeks. The investigators concluded that none of the parameters influenced the clinical remission rates in patients administered with GED-0301, while the rates were higher, compared to patients treated with placebo, which validated the continuation of the studies towards a phase III program.
62.5% of the patients sick for more than five years being treated with GED-0301 160 mg achieved clinical remission at the second week, and 66.7% at the fourth week, while from the ones treated with placebo only 15.4% at week 2 and 4 reached it. Regarding clinical response rates, the researchers verified achievement of 70.8% and 79.2% at the two time indicators respectively from the first group, compared to 19.2% and 26.9% from the second one.
In addition, 62.5% of the patients with a baseline CDAI score of more than 260 reached clinical remission at week 2 through the treatment with GED-0301 160 mg, and 75% at week 4, while the from patients receiving placebo, 13.6% entered clinical remission at week 2 and 4.5% at week 4. The rates of clinical response were 87.5% for the GED-0301 group, compared to 22.7% for the placebo group, at both weeks. The most common adverse effects reported were abdominal pain, Crohn’s disease worsening, urinary tract infection and CRP increase.
The company has also presented results from a phase II clinical trial that evaluated another oral, topically active Smad7 antisense oligonucleotide in patients with active Crohn’s disease. The drug is called Mongersen and was designed to be released at the extremity of the small intestine (the terminal ileum) and near colon extremity (right colon), common areas affected in CD patients. The presentation took place at the United European Gastroenterology Week in Vienna, Austria, in the Section dedicated to New drugs for Inflammatory Bowel Disease.