Pfizer Inc. (NYSE: PFE) announced today that the European Commission (EC) has approved XELJANZ? (tofacitinib) for the treatment of active polyarticular juvenile idiopathic arthritis (JIA) and juvenile psoriatic arthritis (PsA) in patients two years of age and older who have responded inadequately to previous therapy with disease modifying antirheumatic drugs (DMARDs). Two formulations were approved, a tablet and a new oral solution (weight-based dosing). XELJANZ is the first and only Janus kinase (JAK) inhibitor approved in Europe for the treatment of polyarticular JIA and juvenile PsA and has received regulatory approval in four indications in the European Union, the most of any JAK inhibitor.

In addition, the EC has approved XELJANZ prolonged-release 11 mg once-daily tablets for the treatment of adult patients with active PsA who have had an inadequate response or intolerance to methotrexate or other DMARDs. This once-daily treatment is an alternative to the currently approved XELJANZ 5 mg twice-daily treatment of PsA.

"Many patients living with polyarticular juvenile idiopathic arthritis and juvenile psoriatic arthritis require an injection or an infusion when receiving treatment, which can be challenging for both these children and their caretakers," said Ana Paula Carvalho, International Developed Markets Regional President, Inflammation & Immunology at Pfizer. "We are proud to make these new options available in the EU as Pfizer continues to advance the science and understanding of medicines like XELJANZ, which has been studied in more than 50 trials across clinical programs worldwide."

JIA is a chronic inflammatory disease of unknown etiology and is defined as arthritis that begins before 16 years of age and persists for at least six weeks. Polyarticular JIA and juvenile PsA are subtypes of JIA. The polyarticular JIA subtype is characterized by arthritis in five or more joints and affects both the small joints of the hands and feet and large joints like the knees, hips and ankles.i People living with the juvenile PsA subtype can have joint symptoms and a scaly rash of the skin.i It is estimated that JIA impacts approximately 60,000 children in Europe.ii

PsA in adults is a chronic, immune-mediated, inflammatory disease that may include inflammation in peripheral joints, tendons or skin.iii PsA may include a variety of symptoms such as joint pain and stiffness, swollen toes and/or fingers and reduced range of motion.iv

About the JIA Study

The polyarticular JIA and juvenile PsA approval is based on data from a Phase 3 pivotal study in patients with polyarticular JIA as well as other JIA subtypes, including juvenile PsA. The study had two phases: an 18-week open-label, run-in phase (including 225 patients), followed by a 26-week double-blind, placebo-controlled, randomized, withdrawal phase (including 173 patients) for a total duration of 44 weeks. The study evaluated the efficacy and safety of tofacitinib taken as either a 5 mg tablet or as a 1 mg/mL oral solution twice daily based on the subject's body weight (<40 kg for the oral solution) and/or patient preference. The trial met its primary endpoint showing that in patients with polyarticular JIA who achieved a JIA American College of Rheumatology (ACR) 30 response at the end of the run-in phase, the occurrence of disease flare in patients treated with tofacitinib (31 percent; n/M=27/88) was statistically significant (p=0.0007) lower than patients treated with placebo (55 percent; n/N=47/85) at week 44. Efficacy in the juvenile PsA subtype population was consistent with polyarticular JIA. In this study, disease flare was defined as a 30 percent or more worsening in at least three of the six variables of the JIA ACR core set, with no more than one of the remaining JIA core response variables improving by 30 percent or more (outcome measures used in JIA clinical trials) after randomization.v,vi,vii

In general, the types of adverse drug reactions in patients with polyarticular JIA and juvenile PsA were consistent with the known safety profile of XELJANZ. Please see important safety information below.

About XELJANZ? (tofacitinib) and XELJANZ Prolonged Release

XELJANZ (film-coated immediate release tablet, twice daily dosing) is the first and only oral JAK inhibitor approved in the European Union in four indications: adults with moderately to severely active rheumatoid arthritis (RA) after DMARD failure or intolerance, adults with active PsA after DMARD failure or intolerance, adults with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic agent, and active polyarticular JIA and juvenile PsA in patients two years of age and older who have responded inadequately to previous therapy with DMARDs. See Limitations of Use below. In addition, in the European Union, the prolonged release tablet is approved as a once-daily treatment alternative for RA and PsA.

XELJANZ has been studied in more than 50 clinical trials worldwide, including more than 20 trials in RA patients, and prescribed to over 300,000 adult patients (the majority of whom were RA patients) worldwide since 2012.viii,ix,x 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.

In June 2021, the Committee for Medicine Products for Human Use of the European Medicines Agency adopted a recommendation from the Pharmacovigilance Risk Assessment Committee following its review of XELJANZ in the European Union, which states that in patients over 65 years of age, patients who are current or past smokers, patients with other cardiovascular (CV) risk factors, and patients with other malignancy risk factors, XELJANZ should only be used if no suitable treatment alternatives are available. The CHMP-endorsed PRAC recommendation is applicable to all EU member states and is in the process of being implemented in the XELJANZ summary of product characteristics.

Pfizer is also continuing to work with the U.S. Food and Drug Administration (FDA) and other regulatory agencies to review the full results and analysis of the ORAL Surveillance data that has formed the basis of this CHMP-endorsed PRAC recommendation.