Tofacitinib is a Janus Kinase inhibitor under development for the treatment of moderate to severe active rheumatoid arthritis (RA). The Janus Kinases play an important role in the process of inflammation and damage of the joints that occurs in RA. Tofacitinib was expected to be used in patients in whom treatment with at least two other disease-modifying antirheumatic drugs (DMARDs), including biological DMARDs, had been unsuccessful either because patients were unable to tolerate treatment due to side effects, or because they did not respond adequately.
There has been considerable interest in the development of this agent as it is an oral formulation that could potentially be used before biological agents, such as the anti TNFs, which are administered parenterally (sub-cutaneous or intravenous).
The CHMP acknowledged that data from the five main studies showed that treatment with tofacitinib resulted in an improvement in the signs and symptoms of RA and the physical function of patients. However, the studies were not sufficient to show a consistent reduction in disease activity and structural damage to joints, particularly at the lower 5-mg dose of the drug and in the target population of patients in whom treatment with at least two other DMARDs has been unsuccessful. The CHMP also had significant concerns about the overall safety profile of tofacitinib, including unresolved concerns about the risk and type of serious infections observed with the drug. Safety concerns also included an increased risk of other severe side effects including certain cancers, gastro-intestinal perforations, liver damage and problems with increased lipid levels.
According to PharmaTimes, the company (Pfizer) has stated that it intends to appeal this decision and "immediately seek a re-examination of the opinion by the CHMP". A spokesperson for Pfizer told PharmaTimes that 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".
Tofacitinib was approved in the United States for RA in November 2012. The drug has been added to technology appraisal guidance workplan for NICE (expected date TBC).