The European Commission has approved Pfizer‘s Xeljanz (tofacitinib) for the treatment of adults with moderate to severe active ulcerative colitis (UC) who have failed to fully respond to other therapies.
The approved regimen is 10 mg of oral Xeljanz twice a day for at least eight weeks, after which patients can continue on the twice-daily therapy, either at 5 mg or 10 mg.
Approval in the EU follows that of the U.S. Food and Drug Administration for the same indication.
The European Medicines Agency’s Committee for Human Medicinal Products, responsible for assessing the quality, safety, and efficacy of investigational therapies, said that Xeljanz had a clear benefit over other therapies for UC treatment.
“Ulcerative colitis is a chronic disease that can develop at any age, be difficult to manage and affect multiple aspects of daily life,” Angela Lukin, Pfizer’s regional president of inflammation and immunology, said in a press release. “The EC approval of Xeljanz provides an additional treatment option that can help improve the care of adults in Europe living with this debilitating inflammatory bowel disease.”
Xeljanz is a Janus kinase (JAK) inhibitor, which was first approved as a treatment for moderate to severe rheumatoid arthritis and adults with active psoriatic arthritis.
The EC’s decision was based on positive results from the Phase 3 OCTAVE trials — a global clinical program that included three studies, OCTAVE Induction 1 (NCT01458574), OCTAVE Induction 2 (NCT01465763), and OCTAVE Sustain (NCT01458951).
Adults with moderately to severely active UC recruited to the OCTAVE Induction 1 and OCTAVE Induction 2 trials were randomized to a placebo or 10 mg of oral Xeljanz twice daily.
Results from OCTAVE Induction 1 showed that treatment with Xeljanz led to a significantly higher percentage of remission by week eight – 18.5% — compared with patients on a placebo, where remission was only 8.2%.
The OCTAVE Induction 2 trial also showed 16.6% of patients treated with Xeljanz were in remission by the eighth week, compared with the placebo group, at 3.6%.
In both studies, Xeljanz improved mucosal healing by the eighth week.
Patients who responded to the therapy in either one of the trials were invited to enroll in the OCTAVE Sustain study. This trial’s goal was to assess Xeljanz’s effectiveness as a maintenance treatment. Participants received one of two daily doses of oral Xeljanz — 5 mg or 10 mg — or a placebo.
The 52-week trial showed that a significantly larger proportion of patients in both dosage groups achieved remission, compared with the placebo group.
The complete results from the OCTAVE clinical program were published in The New England Journal of Medicine, in a study titled “Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis.”
An ongoing Phase 3 extension study called OCTAVE Open (NCT01470612) is evaluating the effectiveness and safety of Xeljanz’s administered in one of two daily doses — 5 mg or 10 mg — for at least one year.
“Until now, people living with moderately to severely active ulcerative colitis have not had an oral treatment available that can both induce and maintain steroid-free remission,” said Silvio Danese, head of the IBD Center in the department of gastroenterology Humanitas Research Hospital in Milan, Italy, and president of the European Crohn’s and Colitis Organisation Governing Board. “This approval of Xeljanz, the first JAK inhibitor to be approved for this condition, offers the ulcerative colitis community an additional treatment option.”