PHASE 3 OCTAVE STUDIES OF ORAL TOFACITINIB IN ULCERATIVE COLITIS RESULTS PUBLISHED IN THE NEW ENGLAND JOURNAL OF MEDICINE
Data Demonstrated Tofacitinib was Effective as Both Induction and Maintenance Therapy in the Treatment of Moderate to Severe Ulcerative Colitis
Wednesday, May 3, 2017 - 5:25pm EDT “This robust data set provides evidence that tofacitinib, if approved, could be an important new oral treatment option with the potential to help patients with moderate to severe active ulcerative colitis achieve and maintain remission.”
Pfizer Inc. (NYSE:PFE) announced today that detailed results from the Phase 3 Oral Clinical Trials for tofAcitinib in ulceratiVE colitis (OCTAVE) clinical program were published in The New England Journal of Medicine (NEJM).
Data from all three pivotal Phase 3 studies – OCTAVE Induction 1, OCTAVE Induction 2 and OCTAVE Sustain – met their respective primary endpoints, demonstrating that tofacitinib citrate was more effective than placebo in inducing and maintaining remission in patients with moderate to severe ulcerative colitis (UC).1a,1b Remission was defined as a Mayo score* of 2 points or lower, with no individual subscore exceeding 1 point, and a rectal bleeding subscore of 0.1c
“The publication of results from the full Phase 3 OCTAVE clinical program is a significant milestone,” said William J. Sandborn, MD, Chief, Division of Gastroenterology, Professor of Medicine at the University of California San Diego School of Medicine and study investigator. “This robust data set provides evidence that tofacitinib, if approved, could be an important new oral treatment option with the potential to help patients with moderate to severe active ulcerative colitis achieve and maintain remission.”
__________ *Mayo score is a measurement index comprised of four categories (stool frequency, rectal bleeding, findings on endoscopy, physician global assessment) that are each rated from 0 (normal) to 3 (most severe) for a total score that ranges from 0-12.
OCTAVE Induction 1 & 2
OCTAVE Induction 1 and OCTAVE Induction 2 each evaluated induction of remission by oral tofacitinib 10 mg twice-daily (BID) compared to placebo in adult patients with moderate to severe UC.1d The studies enrolled 598 and 541 patients, respectively.1d Eligible patients were randomly assigned to receive eight weeks of therapy with oral tofacitinib 10 mg BID (476 and 429 patients, respectively) or placebo (122 and 112 patients, respectively).1e,1f
In OCTAVE Induction 1, a statistically significant and greater proportion of patients receiving tofacitinib 10 mg BID (18.5%) were in remission at Week 8, compared to 8.2% receiving placebo (p=0.007).1g Similar results were observed in OCTAVE Induction 2, with 16.6% of patients receiving tofacitinib 10 mg BID achieving remission at Week 8, compared to 3.6% receiving placebo (p<0.001).1h
In addition, across each study, a statistically significant and greater proportion of patients receiving tofacitinib 10 mg BID achieved the key secondary endpoint of mucosal healing at Week 8, including 31.3% of patients compared to 15.6% receiving placebo in OCTAVE Induction 1, and 28.4% of patients compared to 11.6% receiving placebo in OCTAVE Induction 2 (p<0.001 across both studies).1i,1j
OCTAVE Sustain
The OCTAVE Sustain study evaluated the efficacy of tofacitinib as maintenance therapy compared to placebo in adult patients with moderate to severe UC.1k It included patients who had completed one of the OCTAVE Induction studies and had achieved at least clinical response (≥3 points reduction and ≥30% decrease from baseline Mayo score plus a decrease in rectal bleeding subscore of ≥1 or absolute rectal bleeding subscore ≤1).1l A total of 593 participants were randomized to receive maintenance treatment with tofacitinib 5 mg BID (198 patients), tofacitinib 10 mg BID (197 patients) or placebo (198 patients) for 52 weeks.1m
In OCTAVE Sustain, 34.3% and 40.6% of patients achieved remission at Week 52 with tofacitinib 5 mg BID and tofacitinib 10 mg BID, respectively, compared to 11.1% taking placebo (p<0.001).1n In addition, both doses of tofacitinib met the key secondary endpoints of the study, mucosal healing and sustained steroid-free remission among baseline remitters.1o Across tofacitinib 5 mg BID, tofacitinib 10 mg BID and placebo arms, mucosal healing was achieved by 37.4%, 45.7% and 13.1% of patients (p<0.001), respectively, and sustained steroid-free remission was achieved by 35.4%, 47.3% and 5.1% (p<0.001), respectively.1o
“Ulcerative colitis is a debilitating disease that affects all aspects of patients’ lives. We are pleased to share the results of this promising clinical trial of tofacitinib as part of our efforts to improve the lives of patients through our research with Janus kinase inhibitors," said Michael Corbo, PhD, Chief Development Officer, Inflammation & Immunology, Global Product Development, Pfizer, Inc. "If approved for this indication, tofacitinib could potentially be an important new oral treatment option for people living with UC.”
During the OCTAVE Induction studies, overall infection and serious infection rates were higher with tofacitinib than placebo.1p In OCTAVE Induction 1, 23.3% and 1.3% of patients receiving tofacitinib 10 mg BID had infections and serious infections, respectively, compared to 15.6% and 0 receiving placebo.1p In OCTAVE Induction 2, 18.2% and 0.2% of patients receiving tofacitinib 10 mg BID had infections and serious infections, respectively, compared to 15.2% and 0 receiving placebo.1p
During OCTAVE Sustain, serious infection rates were similar across treatment groups (1.0%, 0.5% and 1.0% across tofacitinib 5 mg BID, 10 mg BID and placebo groups, respectively).1q Overall infection rates were higher with tofacitinib than placebo (35.9%, 39.8% and 24.2% across tofacitinib 5 mg BID, 10 mg BID and placebo groups, respectively). Cases of herpes zoster were more frequently observed with tofacitinib 10 mg BID compared to other treatment groups (1.5%, 5.1% and 0.5% across tofacitinib 5 mg BID, 10 mg BID and placebo groups, respectively).1q
Across all studies, five tofacitinib-treated patients had adjudicated non-melanoma skin cancer, five had adjudicated cardiovascular events and there were increases in lipids with tofacitinib.1r,1s,1t,1u There were two cases of malignancy in the control groups limited to one case of non-melanoma skin cancer and one case of invasive ductal breast carcinoma during OCTAVE Sustain.1t
The manuscript of full study results, which indicate that tofacitinib citrate was more effective than placebo in inducing and maintaining remission in patients with moderate to severe active UC, is available at http://www.nejm.org/doi/full/10.1056/NEJMoa1606910.
About Ulcerative Colitis
UC is a chronic, often debilitating inflammatory bowel disease that affects millions of people worldwide.2,3 While the exact cause of UC is unknown, it is believed that UC is the result of complex interactions between multiple factors that include genetic predisposition and an exaggerated immune response to a microbial trigger.4 It can cause chronic diarrhea with blood and mucus, abdominal pain and cramping, fever and weight loss.5 UC can have a significant effect on work, family and social activities.6 In up to one-third of patients with UC, treatment is not completely successful or complications may arise.7 Under these circumstances, surgery to remove the colon (colectomy) may be considered.7
About XELJANZ® (tofacitinib citrate)
XELJANZ® (tofacitinib citrate) is a prescription medicine called a Janus kinase (JAK) inhibitor. XELJANZ is approved in more than 80 countries around the world for the treatment of moderately to severely active rheumatoid arthritis (RA). XELJANZ is being investigated for the treatment of moderate to severe UC and is not currently approved for this indication.
As the developer of XELJANZ, Pfizer is a leader in JAK innovation. Pfizer is committed to advancing the science of JAK inhibition and enhancing understanding of XELJANZ through robust clinical development programs in the treatment of immune-mediated inflammatory conditions.
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