Drugs Xagena
The Committee for Medicinal Products for Human Use ( CHMP ) has adopted a negative opinion, recommending the refusal of the marketing authorisation for the medicinal product Xeljanz, intended for the treatment of rheumatoid arthritis.
Xeljanz is a medicine that contains the active substance Tofacitinib. It was to be available as tablets ( 5 and 10 mg ).
Xeljanz was expected to be used in the treatment of moderate to severe active rheumatoid arthritis. It was to be used in patients in whom treatment with at least two other medicines known as disease-modifying antirheumatic drugs ( DMARDs ), including so-called biological DMARDs, had been unsuccessful either because patients were unable to tolerate treatment due to side effects, or because they did not respond adequately.
The active substance in Xeljanz, Tofacitinib, is an immunosuppressant that works by blocking the action of enzymes known as Janus kinases. These enzymes play an important role in the process of inflammation and damage of the joints that occurs in rheumatoid arthritis. By blocking the enzymes, Tofacitinib is expected to reduce the inflammation and other symptoms of the disease.
The company presented the results of five main studies of safety and effectiveness involving over 3,300 patients with rheumatoid arthritis. These studies compared Xeljanz ( in a dose of 5 or 10 mg twice daily ) with placebo, either alone or as an addition to other background medicines ( DMARDs ). The main measures of effectiveness were changes in patient scores for signs and symptoms of disease, physical function of the patient, structural damage to joints and disease activity; these were measured after 3 or 6 months, depending on the study.
The Committee considered that, taken together, the data from the five main studies showed that treatment with Xeljanz resulted in an improvement in the signs and symptoms of rheumatoid arthritis 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 Xeljanz and in the target population of patients in whom treatment with at least two other DMARDs has been unsuccessful.
The CHMP had major concerns about the overall safety profile of Xeljanz. There were significant and unresolved concerns about the risk and type of serious infections seen with Tofacitinib, which are related to the immunosuppressant action of the medicine.
These 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 in the blood. It was not clear that these risks could be managed successfully in medical practice.
Therefore, at that point in time, the CHMP was of the opinion that the benefits of Xeljanz did not outweigh its risks and recommended that it be refused marketing authorisation. ( Xagena )
Source: European Medicines Agency, 2013
XagenaMedicine_2013
