The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a negative opinion for Pfizer's Xeljanz (tofacitinib citrate) for the treatment of adult patients with moderate-to-severe active rheumatoid arthritis (RA). The CHMP is of the opinion that Xeljanz does not demonstrate a favourable risk:benefit profile at this time and recommended against marketing authorization. Pfizer intends to appeal this opinion and immediately seek a re-examination of the opinion by the CHMP.

The Committee considered that treatment with Xeljanz resulted in an improvement in the signs and symptoms of rheumatoid arthritis and the physical function of patients, but did not believe that a consistent reduction in disease activity and structural damage to joints had been sufficiently demonstrated. The CHMP also raised questions about the serious infections, gastrointestinal perforations and malignancies observed in Xeljanz trials.

The Marketing Authorization Application (MAA) included data from the comprehensive, global, multi-study clinical development programme for Xeljanz, which included approximately 5,000 patients across Phase 2 and 3 trials in more than 40 countries, resulting in 7,000 patient-years of exposure. The application was based on the same pivotal efficacy and safety data package that was provided to regulatory agencies around the world. Xeljanz is approved in the United States, Japan and Russia for the treatment of adults with moderate-to-severe active RA.

“We have confidence in Xeljanz and believe our application to the EMA demonstrates that Xeljanz has a favorable risk:benefit profile. Xeljanz’s safety profile is well-characterized, and the issues raised by the EMA, including serious infections, gastrointestinal perforations and malignancies, are familiar to rheumatologists who are experienced working with treatments for patients to manage this difficult disease,” said Dr Yvonne Greenstreet, senior vice president and the head of the Medicines Development Group for Pfizer Specialty Care. “Each regulatory authority will review and interpret applications individually and different assessments are not uncommon. The re-examination process will enable us to seek to address the CHMP’s questions, and we will continue to work closely with the EMA with the goal of making this medicine available to appropriate patients in Europe.”

Xeljanz is a novel, oral Janus kinase (JAK) inhibitor for the treatment of RA. Unlike recent therapies for RA, which are directed at extracellular targets such as pro-inflammatory cytokines, Xeljanz takes a novel approach targeting the intracellular pathways that operate as hubs in the inflammatory cytokine network.