Pfizer, Inc., recently announced that its investigational oral drug tofacitinib has met primary and key secondary endpoints in two Phase 3 studies evaluating its efficacy and safety in inducing remission in adult patients with moderately to severely active ulcerative colitis (UC). The results were given in oral presentations at the recent 11th Congress of the European Crohn’s and Colitis Organisation (ECCO).
The OCTAVE (Oral Clinical Trials for tofAcitinib in ulceratiVE colitis) global clinical development program includes three Phase 3 studies, OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain. The program also includes a long-term extension trial, the OCTAVE Open. OCTAVE Induction 1 and OCTAVE Induction 2, two identical placebo-controlled Phase 3 studies, aimed to evaluate the efficacy of oral tofacitinib 10 mg twice daily in inducing remission, as defined by a Mayo score of 2 points or lower and a rectal bleeding subscore of 0, in adults with moderately to severely active UC. The disease is complicated to treat as many patients are unresponsive or become intolerant to traditional therapies.
Both studies’ primary endpoints were met. In OCTAVE Induction 1, at week eight, significantly more patients (18.5 percent) receiving tofacitinib achieved remission in comparison to those receiving placebo (8.2 percent). Likewise, in OCTAVE Induction 2 at week eight, significantly more patients (16.6 percent) receiving tofacitinib were in remission than those receiving placebo (3.6 percent).
Moreover, a greater number of patients under the drug treatment in both studies achieved mucosal healing at week eight, the secondary key endpoint. In OCTAVE Induction 1, 31.3 percent of those receiving tofacitinib, and 15.6 percent of patients treated with placebo, achieved mucosal healing. The results in OCTAVE Induction 2 were consistent, with 28.4 percent of patients under tofacitinib treatment achieving mucosal healing, compared to 11.6 percent of patients receiving a placebo.
Rates of adverse events (AEs) and serious AEs (SAEs) in OCTAVE Induction 1 were 56.5 percent and 3.4 percent, respectively, in the tofacitinib group compared to 59.8 percent and 4.1 percent in the placebo group. In OCTAVE Induction 2, rates of AEs and serious AEs were 54.1 percent and 4.2 percent in the tofacitinib group, compared to 52.7 percent and 8.0 percent in the placebo group.
“We are encouraged by the results from the OCTAVE Induction studies, as they showed that in these trials oral tofacitinib reduced the symptoms of moderate to severe ulcerative colitis and induced remission of the disease. What’s more, these results were seen in patients who were previously treated with tumor necrosis factor inhibitors (TNFis) as well as those who had not received treatment with TNFis. And, improvements in symptoms were observed as early as week 2, the first time point it was measured,” the study investigator, Dr. Geert D’Haens, MD, professor of Gastroenterology at The Academic Medical Center, University of Amsterdam, said in a press release.
Results from OCTAVE Sustain are expected in late 2016.
Pfizer’s oral drug tofacitinib, available under the brand name Xeljanz, is already approved in the U.S. and elsewhere as a second-line treatment for adults with moderately to severely active rheumatoid arthritis who fail to respond to methotrexate.