The European Commission has approved the use of Orencia (abatacept) by intravenous infusion and injection in combination with methotrexate (MTX) to treat highly active and progressive rheumatoid arthritis (RA) in adults not previously treated with MTX.
The EC approval allows Bristol-Myers Squibb to expand RA marketing of Orencia in the 28 European Union countries.
The U.S. Food and Drug Administration (FDA) originally approved Orencia by IV infusion for adults with RA in December 2005, and by a self-injectable formulation in 2011.
The latest European Commission approval was based on two Phase 3 clinical trials conducted for Orencia in adults with high disease activity (a mean Disease Activity Score, or DAS28-CRP, of 5.4) and poor prognostic factors for rapidly progressive disease, such as the presence of anti-CCP antibodies or RF+, as well as the presence of baseline joint erosions.
The first study, called AGREE, was a multinational trial following MTX-naive patients with early and progressive RA for one year.
Researchers observed that, compared to MTX alone, the combination of Orencia (intravenous) with MTX induced significant efficacy in patients with moderate to severe RA. In other words, after one year of treatment, more patients in the Orencia plus MTX group achieved DAS28-defined remission of the disease and presented less radiographic progression, meeting the endpoint of the study.
The most common side effects reported in the AGREE trial were headaches, infections of the upper respiratory tract (nose, pharynx, and larynx), colds and nausea. These side effects were reported in fewer than 10 percent of the patients.
The second Phase 3 study, called AVERT, followed 351 adult patients with moderate to severe early RA for one year. Patients were divided into one of three experimental groups: combination of Orencia 125 mg subcutaneous with MTX; Orencia 125 mg subcutaneous alone; and MTX alone. These patients had never been treated with MTX or other disease-modifying, anti-rheumatic drugs (DMARDs).
After one year of treatment, compared to MTX alone, significantly more patients achieved DAS28-defined remission, as well as in other indexes of RA remission (Boolean, CDAI, and SDAI), when treated with the combined therapy of Orencia and MTX.
In addition to these two trials, results from X-rays and MRI evaluations of structural and inflammatory markers of disease severity were also obtained to support the approval of Orencia as a treatment for RA in the European Union.
Orencia can be used alone or combined with DMARDs by adults and children ages 6 and older, but is not recommended to be used simultaneously with other RA therapies, such as anakinra, or tumor necrosis factor (TNF) antagonists.
“Across the globe we remain committed to advancing care for those living with RA,” Brian Gavin, a BMS vice president and Orencia development lead, said in a news release. “The European Commission’s approval of Orencia in the EU for MTX-naive RA patients who have highly active and progressive disease is a testament to Bristol-Myers Squibb’s commitment to advancing the science of earlier identification of patients with progressive RA prior to their suffering debilitating joint damage.”