One of the landmark rites of passage for any closely watched therapy is the point that Phase II data is published in a journal and given a once-over by an expert, critical eye. And Celgene ($CELG) just got both an endorsement as well as a few challenges in a review of the midstage study for mongersen, an experimental drug for Crohn's disease that will soon be part of the big biotech's late-stage pipeline, with a Phase III study looming.
Based on these Phase II numbers, Celgene paid $710 million upfront to partner with the unknown Nogra on mongersen in a deal package worth upwards of $2.6 billion--one of the richest single-product partnership deals in the industry. And the independent review makes clear that Celgene has a shot at beating out some of the biggest blockbusters on the market, including Remicade and Enbrel.
Writing in The New England Journal of Medicine, Severine Vermeire from University Hospitals, Leuven, Belgium noted that the Phase II data were remarkable for a variety of reasons, including the high rate of remission that was seen among patients receiving the two highest doses of the drug and evidence that the drug may be incredibly durable, with remission maintained for three months after 14 days of treatment.
"If confirmed in future studies," writes Vermeire, "this durable effect of mongersen would be unprecedented and would represent a first step toward curing the disease."
The data were released earlier, but it's worth repeating. In the 40-mg and 160-mg mongersen groups, 55% and 65% of the patients hit the primary endpoint, compared to only 10% in the placebo arm and a statistically equivalent 12% response in the low-dose 10-mg arm.
The Crohn's expert also noted that "the remission rates of between 55 and 65% for the two highest doses are unprecedented when compared with those reported in the large pivotal induction studies of infliximab (Remicade) (32.5% glucocorticoid-free clinical remission at week 6 in the SONIC trial), adalimumab (Humira) (36% clinical remission at week four in the CLASSIC-I trial), and more recently, vedolizumab (Entyvio) (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."
But the review doesn't come without some concerns that Celgene will have to address in Phase III, if it wants to get through its FDA review in one piece.
Roughly four out of 10 patients in the study had normal levels of C-reactive protein, a biomarker for the severity of the disease. Vermeire thought that figure was unusually high, indicating that the investigators were able to clear the bar on efficacy with a patient group that may have been skewed to milder cases more likely to go into remission. She also questioned the inclusion criteria used for the 160 patents in the study while puzzling out why an endpoint like mucosal healing was excluded. In addition, she noted that there was a high remission rate with a relatively low reduction in C-reactive protein levels, a contrast in results on a key biomarker that needs to be explored.
Overall, the review confirms the promise that drew Celgene in, and the hurdles that remain in the big Phase III that awaits investigators.
"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."
- here's the release
- read the review