Filgotinib induces remission in moderate-to-severe Crohn's disease

Last Updated: 2016-12-21

By Will Boggs MD

NEW YORK (Reuters Health) - The JAK1-selective inhibitor filgotinib induces clinical remission in moderate-to-severe Crohn's disease, according to results from the mid-stage FITZROY study.

"This is the first evidence that JAK inhibitors (as a class) - in this particular case, a selective JAK1 - offers benefit in Crohn's disease," Dr. Severine Vermeire from University Hospitals Leuven, Belgium told Reuters Health by email. "Furthermore, the data in this relatively small phase 2 study were very consistent and observed for all studied outcomes of clinical remission, response, CRP decrease, and mucosal healing."

Janus kinases (JAKs) appear to play a key role in inflammatory bowel disease, but another pan-JAK inhibitor, tofacitinib, was no more effective than placebo in randomized studies in Crohn's disease.

Dr. Vermeire and colleagues examined the efficacy and safety of once-daily oral filgotinib in 174 patients with active, moderate-to-severe Crohn's disease.

At week 10, 47% of patients in the filgotinib group achieved clinical remission, compared with 23% of patients in the placebo group (p=0.0077), according to the December 14th Lancet online report.

Filgotinib appeared to be more effective among anti-TNF-naïve patients (60% achieved clinical remission) than among anti-TNF-experienced patients (37% achieved clinical remission).

More patients in the filgotinib group achieved reductions in the Crohn's Disease Activity Index in excess of 100 points, and there was a greater improvement from baseline in total Inflammatory Bowel Disease Questionnaire scores with filgotinib than with placebo.

Moreover, a greater proportion of patients treated with filgotinib achieved endoscopic responses, endoscopic remission, and deep remission at week 10, although the differences fell short of statistical significance.

Similar proportions of patients in the filgotinib and placebo groups experienced treatment-emergent adverse events.

"I see this drug as an induction and maintenance agent for patients who fail steroids and/or immunosuppressants," Dr. Vermeire said. "Its oral dosing, furthermore, could well place (it) before biologics in the future, on the condition of course that the phase 3 studies confirm the benefit and good safety profile."

"Although I am really excited about the recent progress in drug development for both Crohn's disease and ulcerative colitis, we are still far from a cure," she said, "and, therefore, we need also to invest in translational research defining patient subgroups and profiles who would benefit most from certain drugs or classes of drugs."

Dr. Ashwin N. Ananthakrishnan from Massachusetts General Hospital and Harvard Medical School in Boston, who wrote an editorial related to this report, told Reuters Health by email, "I think the results are interesting because it is a new mechanism of action in Crohn's disease. It is all the more interesting because a previous JAK inhibitor trial (tofacitinib) had shown more equivocal results."

"The other benefit is that this could potentially be a nice oral therapy option in Crohn's disease, which is useful since many of the recently approved therapies (are) IV or injectable options," he said.

Dr. Ole Haagen Nielsen from University of Copenhagen, Herlev, Denmark, who recently reviewed targeted therapies for inflammatory bowel disease, told Reuters Health by email, "None of the existing conventional treatments for managing CD are ideal due to lack of effect, side effects, or cumbersome administration, and both patients and the society are interested in more targeted/personalized medications which are easy to administer without hidden costs associated with intravenous management, encompassing scheduled infusion visits, the need for infusion specialized administrative staff, consumables, and special storage conditions that characterize biologics."

"Accordingly," he said, "more easily administered medications (i.e., oral tablets) are warranted. In this way, filgotinib may be one among several novel oral drugs for future therapy of Crohn's disease."

"Actually, filgotinib is not the only easily administered oral drug in the pipeline for Crohn's disease, but is one among several others at the moment (e.g. mongersen, ozanimod, amiselimod, and laquinimod)," Dr. Nielsen added.

Dr. Laurent Peyrin-Biroulet, head of the inflammatory bowel disease unit at Nancy University Hospital in France, told Reuters Health by email, "Several JAK inhibitors will be approved soon for IBD; JAK selectivity and associated risk-benefit ratio could be the key. We will need to wait for the results of large post-marketing cohorts to better assess their safety profile."

He suggests that anti-TNF treatments may remain first-line, despite lower efficacy, depending on the eventual cost of the JAK inhibitors.

Galapagos NV funded the study, employed 3 of the 15 authors, and had various relationships with the other 12 authors.

According to a Galapagos news release, a phase 3 study in Crohn's disease started last month and a phase 2/3 study of filgotinib for ulcerative colitis began this month.

SOURCE: http://bit.ly/2i1wLLp and http://bit.ly/2hd8bun

Lancet 2016.