The FINANCIAL — Bristol-Myers Squibb Company on September 5 announced that the European Commission has approved ORENCIA (abatacept) intravenous (IV) infusion and subcutaneous (SC) injection, in combination with methotrexate (MTX), for the treatment of highly active and progressive disease in adult patients with rheumatoid arthritis (RA) not previously treated with MTX.
With this approval, ORENCIA is the first biologic therapy with an indication in the European Union (EU) specifically applicable to the treatment of MTX-naive RA patients with highly active and progressive disease. Studies of ORENCIA involving adult patients with high disease activity (mean DAS28-CRP of 5.4) accompanied by poor prognostic factors for rapidly progressive disease (positive for anti-CCP antibodies (also known as ACPA), and/or RF+, presence of baseline joint erosions) provided the clinical trial evidence supporting the recommendation. This approval allows for the expanded marketing of ORENCIA in all 28 Member States of the EU, according to Bristol-Myers Squibb Company.
“Across the globe we remain committed to advancing care for those living with RA. 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,” said Brian J. Gavin, Vice President, ORENCIA Development Lead at Bristol-Myers Squibb.
The approval was based on data from two Phase 3 studies: In a 12 month, multinational, double-blind, randomized, Phase 3B study of MTX-naive patients with early, rapidly progressing RA, ORENCIA IV + MTX demonstrated significant efficacy vs MTX alone for those with moderate to severe RA. The study, AGREE (Abatacept study to Gauge Remission and joint damage progression in MTX-naive patients with Early Erosive RA), met its co-primary endpoints as defined by the proportion of patients achieving DAS28-CRP < 2.6 at 1 year (41% vs 23%, P<0.001) and inhibition of radiographic progression at 1 year (mean change in total Sharp score: 0.6 vs 1.1, P=0.04). Headache, upper respiratory tract infection, nasopharyngitis, and nausea were the most commonly reported adverse events occurring at a rate of ≥ 10% in patients taking ORENCIA in the adult RA clinical studies.
The second Phase 3 data is from the AVERT (Assessing Very Early Rheumatoid Arthritis Treatment) study, which compared ORENCIA 125 mg subcutaneous + MTX combination therapy, ORENCIA 125 mg subcutaneous monotherapy, and MTX monotherapy in induction of DAS28-defined remission following 12 months of treatment in 351 adult patients with moderate to severe active, early RA (mean DAS28-CRP of 5.4; mean symptom duration less than 6.7 months) who had not been treated with MTX or other DMARDs earlier (MTX-naive).2 Patients also had poor prognostic factors for rapidly progressive disease (positive for anti-CCP antibodies, and/or RF+, presence of baseline joint erosions).2 The co-primary endpoints compared the proportion of patients with DAS28-defined remission (DAS28 CRP <2.6) at month 12 and both months 12 and 18 for ORENCIA + MTX versus MTX alone.2 At 12 months, significantly more patients on ORENCIA combination therapy achieved DAS28-defined remission than MTX alone (60.9%, ORENCIA + MTX; 45.2%, MTX alone).2 Similar results at 12 months were seen with other measures of efficacy including Boolean remission (37.0%, ORENCIA + MTX; 22.4%, MTX alone), CDAI remission (42%, ORENCIA + MTX; 27.6% MTX alone), and SDAI remission (42%, ORENCIA + MTX; 25% MTX alone). The European Commission’s approval is based on clinical response to ORENCIA as well as X-Ray and MRI assessments of structural and inflammatory measures of disease severity.