Celgene announced that its investigational Crohn’s disease drug was successful in its mid-stage trial, meeting the primary endpoint of clinical remission.
The company said that results from the Phase II trial of three doses of GED-0301 (mongersen) in patients with active Crohn’s disease were published in The New England Journal of Medicine (NEJM). In addition to positive study results, NEJM published an accompanying editorial by an expert which said the clinical effects of the drug were impressive and suggests that mongersen could herald a “new phase of Crohn’s disease treatment.” However, the review did include a few challenges and questions that need to be addressed in future trials.
The Phase II trial enrolled 166 adult patients with moderate-to-severe Crohn’s disease, defined as Crohn’s Disease Activity Index (CDAI) ranging from 220 to 400 at least one week prior to enrollment, with documented inflammatory lesions in the terminal ileum and/or right colon. The results from this study showed that a significantly greater proportion of patients with active Crohn’s disease achieved the primary endpoint of clinical remission at both day 15 and day 28 with once-daily mongersen 40 mg (55 percent) or 160 mg (65 percent) than with mongersen 10 mg (12 percent) or placebo (10 percent).
In the accompanying editorial, Severine Vermeire from the University Hospitals, Leuven, Belgium, said that these remission rates for the two highest doses are unprecedented when compared to those reported in the large pivotal induction studies of Remicade and Humira. However, Vermeire noted that patients in Celgene’s study may have had more moderate disease, making it easier to induce remissions. Additionally, she said that the median level of C-reactive protein, a biomarker for the severity of the disease, among patients at the beginning of the study was surprisingly low, and 39 percent of patients did not have elevated levels. She said that, although not all Crohn’s disease patients have elevated C-reactive protein levels, 39 percent of trial participants with normal levels seem unusually high.
She also questioned the choice of study endpoints. While clinical response and remission are endpoints recommended by regulatory authorities for patients with inflammatory bowel disease, there has been increasing emphasis on endpoints such as mucosal healing, which was excluded from Celgene’s trial.
Overall, in her review Vermeire confirms the promise of Celgene’s drug but says that follow-up studies are needed to confirm results.
“A significant number of Crohn’s disease patients don’t reach remission with current therapies and are looking for additional options,” said Scott Smith, President of Celgene Inflammation and Immunology. “GED-0301 offers a completely different mechanism of action that has the potential to transform the Crohn’s treatment landscape. We are encouraged by the phase II data and are committed to bringing innovative medicine to patients with Crohn’s disease, starting with advancing the phase III trial for GED-0301.”
In April 2014, Celgene entered into a global license agreement with privately-held Nogra Pharma Limited, to develop and commercialize mongersen. For the treatment of Crohn’s disease and other indications. Celgene paid Nogra $710 million upfront, with a promise of up to $815 million in milestone payments.
Sources: Celgene Corporation; New England Journal of Medicine
Last updated: 3/19/15; 12:15pm EST