Xeljanz (tofacitinib) has become the first medication in its class to be approved by the U.S. Food and Drug Administration (FDA) as a treatment for polyarticular juvenile idiopathic arthritis (pJIA).
The FDA approved two formulations of Pfizer‘s medication — a tablet and an oral solution — for use in people, age 2 and older, with active pJIA. The tablet will be available to patients in the U.S. immediately, with the solution expected to become available in early 2021. Dosing is determined based on an individual’s weight.
“Many children and adolescents living with polyarticular course juvenile idiopathic arthritis, or pcJIA, are in need of advanced oral treatment options, so we are proud to now offer XELJANZ to this patient community,” Michael Corbo, PhD, chief development officer of inflammation and immunology at Pfizer Global Product Development, said in a press release.
The approval “reinforces [Xeljanz’s] utility in the treatment of immune-mediated inflammatory conditions,” he added.
Xeljanz is an oral small molecule designed to inhibit janus-activated kinase (JAK), an enzyme that plays a central role in the activation of certain inflammatory signals. The therapy has previously been approved in the U.S. and the European Union for the treatment of adults with rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis.
The new approval is based on results from a Phase 3 clinical trial (NCT02592434), sponsored by Pfizer, which included 225 children and adolescents with JIA, among which 184 had pJIA.
In the first 18 weeks of the trial, all participants were treated with Xeljanz. At that point, only the 173 participants who had a clinical response to the treatment were randomly assigned to continue on Xeljanz or to take a placebo for the next 26 weeks, while patients who did not respond to Xeljanz discontinued the study.
Clinical response was defined as fulfilling the ACR30 criteria, meaning a 30% improvement or reduction in three of the following: patient/parent assessment of overall well-being, physician assessment of disease activity, functional ability, number of tender and swollen joints or those with limited range of motion, and inflammation. Also, only one variable could worsen by more than 30%.
In turn, pJIA flares were defined as 30% or more worsening in at least three of the six ACR variables, with no more than one remaining variable improving by at least 30%.
The study met its primary goal: the occurrence of JIA flares at the end of the 44-week study was significantly lower in participants treated with Xeljanz than in patients given a placebo (31% vs. 55%).
Treatment also led to stable disease, in contrast to the worsening seen in the placebo group.
Adverse reactions were similar to what has previously been seen in adults with rheumatoid arthritis. Common adverse events in both Xeljanz and placebo groups included nasopharyngitis (the common cold), upper respiratory tract infection, nausea, and headache.
Xeljanz is now the first and only JAK inhibitor approved to treat pJIA in the U.S.
“Although there are already several advanced treatments available, tofacitinib [Xeljanz] will be an appealing new option given it does not require injections or infusions. These can be quite burdensome to both children with pcJIA and their caretakers,” said Hermine Brunner, MD, director of the division of rheumatology at Cincinnati Children’s Hospital Medical Center, who served as an investigator on the Phase 3 clinical trial.
“The FDA approval of Xeljanz for pcJIA is positive news for this community as it provides a new advanced treatment option in an oral formulation,” she added.