The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has confirmed its opinion to recommend against approval of Pfizer Inc.'s Xeljanz (tofacitinib citrate) for treatment of adult patients with moderate-to-severe active rheumatoid arthritis (RA). After re-examination of the application as requested by Pfizer, the CHMP is of the opinion that Xeljanz does not demonstrate a favourable benefit:risk profile.

While the CHMP considered that treatment with Xeljanz resulted in reduction in the signs and symptoms of RA and improvement in the physical function of patients, it has outstanding concerns on safety, including serious infections.

The company is currently evaluating the feedback from the CHMP and will determine next steps to resubmit a MAA to the EMA.

“We are disappointed in the outcome of the re-examination process. A narrow majority of the CHMP felt there is too limited experience in the patient population to fully characterize the profile of Xeljanz and the Committee did not recommend approval at this time,” said Dr Steven Romano, senior vice president and the head of the Medicines Development Group for Pfizer Specialty Care.  “The clinical experience with Xeljanz to date, which includes data from approximately 5,000 patients treated for RA, demonstrates a consistent efficacy and safety profile across a range of patient types and a risk profile that is familiar to rheumatologists who have experience utilizing the range of treatments available to treat this disease. We believe that the benefit:risk profile of Xeljanz is favourable, and we remain committed to working with the EMA to make Xeljanz available to appropriate patients in Europe.”

The MAA included data from the comprehensive, global, multi-study clinical development programme for Xeljanz, which included approximately 5,000 patients across phase II and phase III trials in more than 40 countries, resulting in 7,000 patient-years of exposure at the time of regulatory submission. The application was based on the same pivotal efficacy and safety data package that was provided to regulatory agencies around the world.

RA is a chronic inflammatory autoimmune disease that typically affects the hands and feet, although any joint lined by a synovial membrane may be affected.

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. Xeljanz is approved in the United States, Japan, Argentina, Kuwait, Russia, Switzerland and the United Arab Emirates for the treatment of adults with moderate-to-severe active RA.

Pfizer strives to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Its global portfolio includes medicines and vaccines as well as many of the world's best-known consumer health care products.