The U.S. Food and Drug Administration (FDA) has approved the oral therapy Xeljanz (tofacitinib), by Pfizer, to treat adults with moderately to severely active ulcerative colitis (UC), the company announced.
The treatment regimen calls for taking Xeljanz twice a day at 10 mg for at least eight weeks, after which patients can continue on the twice-daily therapy, either at 5 mg or 10 mg.
“The FDA approval of XELJANZ is positive news for the ulcerative colitis community, a patient population that can often encounter frequent and debilitating disruptions to their daily lives,” William J. Sandborn, MD, Chief, Division of Gastroenterology at the University of California San Diego School of Medicine and investigator in the trials that supported the approval, said in a press release. “XELJANZ provides people living with ulcerative colitis and their prescribing physicians with a new oral treatment option.”
The approval follows a recent recommendation from FDA’s advisory panel – the Gastrointestinal Drugs Advisory Committee (GIDAC) – whose members voted unanimously (15–0) to extend the induction dosage period of Xeljanz (10 mg twice a day) from eight weeks to 16 weeks for UC patients who have failed to respond fully to the treatment after eight weeks.
Committee members also voted unanimously (15–0) in favor of continuous treatment with Xeljanz, again at 10 mg doses twice daily, for adults who have had a poor response, a loss of response, or are intolerant to anti-tumor necrosis factor (TNF) therapy.
Xeljanz is a Janus kinase (JAK) inhibitor, previously approved by the FDA to treat moderate to severe rheumatoid arthritis (RA) and adults with active psoriatic arthritis (PsA).
The FDA based its decision on results from the OCTAVE global clinical development program that included three Phase 3 studies – OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain.
The placebo-controlled Phase 3 studies, OCTAVE Induction 1 and OCTAVE Induction 2, evaluated the efficacy of oral Xeljanz 10 mg twice daily in inducing remission, defined as a Mayo score of 2 points or lower and a rectal bleeding subscore of 0, in adults with moderately to severely active UC.
Both studies achieved their primary goals: in the OCTAVE Induction 1, a significantly higher percentage of patients treated with Xeljanz achieved remission by week eight – 18.5 percent — versus 8.2 percent in those given placebo.
Likewise, in OCTAVE Induction 2 at week eight, 16.6 percent of tofacitinib-treated patients were in remission compared to 3.6 percent of placebo controls.
In both studies, patients treated with Xeljanz also showed signs of mucosal healing by week eight (a secondary trial goal or endpoint).
Patients who completed and achieved clinical response in either OCTAVE Induction 1 or OCTAVE Induction 2 studies enrolled the OCTAVE Sustain study, where researchers evaluated Xeljanz’s efficacy as maintenance treatment.
The 52-week trial evaluated two daily doses of oral Xeljanz (5 mg and 10 mg) against placebo.
Results showed that a significantly larger proportion of patients achieved remission of ulcerative colitis at week 52, the study’s primary efficacy point, in both dosage groups compared to a placebo.
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.”
“Ulcerative colitis is a chronic inflammatory bowel disease that can significantly impact the lives of patients and has limited therapeutic options available,” said Michael Goettler, Global President, Inflammation and Immunology, at Pfizer. “With the FDA approval of XELJANZ, adults living with moderately to severely active UC now have an oral option that may help achieve and maintain steroid-free remission.”
An ongoing Phase 3 study, OCTAVE Open (NCT01470612), is a large (946 participants) and long-term extension trial assessing the effectiveness and safety of Xeljanz’s two daily doses – 5 mg and 10 mg – taken at least one year.
“What works for one ulcerative colitis patient may not work for another and some struggle with ongoing symptoms. That is why it is so critical that our patients have different treatment options available to them,” said Michael Osso, president & CEO of the Crohn’s & Colitis Foundation. “We are thrilled to have this new treatment option available to ulcerative colitis patients. Every new treatment provides new hope to our community.”
The European Medicines Agency (EMA) is also reviewing Xeljanz as a potential treatment of adults with ulcerative colitis.