Pfizer Announces Results from XELJANZ® XR (tofacitinib) ORAL Shift Study, The First Phase 3b/4 Study to Evaluate Methotrexate Withdrawal with a JAK Inhibitor

Results to be Presented During a Late-Breaking Oral Session at the Annual European Congress of Rheumatology (EULAR 2019)

NEW YORK, NY, USA I June 12, 2019 I Pfizer Inc. (NYSE:PFE) announced today positive results from ORAL Shift, a Phase 3b/4 study in adult patients with moderately to severely active rheumatoid arthritis (RA). Patients who achieved low disease activity (LDA) with XELJANZ® (tofacitinib) extended release (XR) 11 mg once daily (QD) plus methotrexate (MTX) after a 24-week open-label run-in period, were randomized to evaluate the efficacy and safety of XELJANZ XR 11 mg QD as monotherapy after MTX withdrawal compared with XELJANZ XR with continued MTX. The study demonstrated non-inferiority of MTX withdrawal with XELJANZ XR 11 mg QD compared to XELJANZ XR 11 mg QD plus MTX at week 48 as measured by the primary endpoint, the change in the Disease Activity Score (DAS28-4[ESR]) from randomization at week 24 to the end of the double-blind MTX withdrawal phase at week 48. The study results will be presented during a late-breaking oral session at the Annual European Congress of Rheumatology (EULAR 2019) in Madrid, Spain (15 June).

“The results of ORAL Shift provide important information on the use of XELJANZ XR as monotherapy after methotrexate withdrawal, which is significant as some people living with rheumatoid arthritis are unable or unwilling to use methotrexate,” said Stanley Cohen, MD, Metroplex Clinical Research Center, Dallas, TX. “From a clinical perspective, these results give physicians data to help inform the decision to take appropriate patients off methotrexate.”

Efficacy Results

For the primary efficacy analysis, patients who achieved Clinical Disease Activity Index (CDAI) low disease activity at week 24 were randomized into the MTX withdrawal phase resulting in least squares (LS) mean changes in DAS28-4(ESR) from weeks 24 to 48 of 0.33 and 0.03 in the XELJANZ XR monotherapy and XELJANZ XR plus MTX groups, respectively [LS mean difference = 0.3; 95% CI, 0.12-0.48; non-inferiority p<0.0005]. The primary analysis showed that XELJANZ XR 11 mg QD monotherapy was non-inferior to XELJANZ XR 11 mg QD with MTX at week 48.

“ORAL Shift exemplifies Pfizer’s commitment to ongoing JAK research with the goal of meeting the evolving needs of patients living with this chronic inflammatory condition,” said Michael Corbo, Chief Development Officer, Inflammation & Immunology, Pfizer Global Product Development. “We are extremely pleased with the findings from ORAL Shift, which to date is the only non-inferiority study to evaluate and demonstrate the efficacy of a JAK inhibitor after methotrexate withdrawal in adults with moderately to severely active RA who achieved low disease activity after combination therapy.”

Safety Results

The safety findings in ORAL Shift include the most frequently reported adverse events (AEs) for each study group in the double-blind treatment period of nasopharyngitis, upper respiratory tract infection and bronchitis. Rates of AEs, serious AEs (SAEs) and discontinuations due to AEs were generally comparable between treatment arms. In the XELJANZ XR monotherapy group, there were 10 SAEs and 5 discontinuations due to AEs. In the XELJANZ XR plus MTX group, there were 5 SAEs and 5 discontinuations due to AEs. During the double-blind withdrawal phase of the study, AEs were reported in 40.5% of patients (n=107) in the XELJANZ XR monotherapy treatment group and 41.0% of patients (n=109) in the XELJANZ XR plus MTX treatment group. In addition, SAEs were reported in 3.8% of patients (n=10) in the XELJANZ XR monotherapy treatment group and 1.9% of patients (n=5) in the XELJANZ XR plus MTX treatment group. In the double-blind treatment period, there were two deaths reported in the XELJANZ XR plus MTX treatment group. The full Prescribing Information for XELJANZ/XELJANZ XR includes a BOXED WARNING for serious infection and malignancy.

About the Study

ORAL Shift was a 12-month randomized, double-blind, placebo-controlled, non-inferiority, methotrexate (MTX) withdrawal study in subjects with moderate to severe rheumatoid arthritis (RA) who were also inadequate responders to treatment with MTX alone. The study included 694 patients with moderate to severe RA. During the run-in phase, all patients received open-label XELJANZ XR 11 mg QD plus MTX using their previously stabilized MTX dose. At week 24, patients who achieved low disease activity (LDA) as assessed by CDAI (n=530) were randomized into the 24-week double-blind, placebo-controlled MTX withdrawal phase, for a total of 48 weeks. The primary efficacy endpoint was the difference between the two treatment groups in change in DAS28-4(ESR). Change was measured from the time of randomization, at Week 24, to the end of the double-blind MTX withdrawal phase at Week 48. In the double-blind phase, subjects were randomized in a 1:1 ratio to either continue on XELJANZ XR plus MTX (n=266) or to receive XELJANZ XR monotherapy plus blinded matching placebo for MTX (n=264).

About XELJANZ® (tofacitinib)

XELJANZ® (tofacitinib) is approved in the U.S. for adult patients in three indications: moderately to severely active rheumatoid arthritis (RA), active psoriatic arthritis (PsA) and moderately to severely active ulcerative colitis (UC). Globally, XELJANZ is approved in more than 130 countries for the treatment of moderately to severely active RA and has been prescribed to an estimated 205,000 patients.

As the developer of tofacitinib, Pfizer is committed to advancing the science of JAK inhibition and enhancing understanding of tofacitinib through robust clinical development programs in the treatment of immune-mediated inflammatory conditions.

INDICATIONS

Rheumatoid Arthritis

  • XELJANZ/XELJANZ XR (tofacitinib) is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. It may be used as monotherapy or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs).
  • Limitations of Use: Use of XELJANZ/XELJANZ XR in combination with biologic DMARDs or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

Psoriatic Arthritis

  • XELJANZ/XELJANZ XR (tofacitinib) is indicated for the treatment of adult patients with active psoriatic arthritis who have had an inadequate response or intolerance to methotrexate or other disease-modifying antirheumatic drugs (DMARDs).
  • Limitations of Use: Use of XELJANZ/XELJANZ XR in combination with biologic DMARDs or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

Ulcerative Colitis

  • XELJANZ (tofacitinib) is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC).
  • Limitations of Use: Use of XELJANZ in combination with biologic therapies for UC or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

Pfizer Inc.: Breakthroughs that change patients’ lives®

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world's best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com. In addition, to learn more, please visit us on www.pfizer.com and follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.

SOURCE: Pfizer

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