FDA approves subcutaneous formulation of abatacept for treatment of RA

FDA has approved a subcutaneous (SC) formulation of abatacept (Orencia, Bristol-Myers Squibb) for the treatment of adults with moderate-to-severe rheumatoid arthritis (RA). It is the first biologic available in both SC and intravenous (IV) formulations for the treatment of RA.

Orencia is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis. Orencia may be used as monotherapy or concomitantly with disease-modifying antirheumatic drugs (DMARDs) other than tumor necrosis factor (TNF) antagonists. Since the majority of RA patients initiating therapy with a biologic receive their treatment by SC injection, the approval of Orencia SC offers physicians a choice for more of their patients.

The new self-injectable formulation is a fixed 125-mg dose administered weekly through an injection under the skin following a single IV loading dose of approximately 10 mg/kg. Patients who are unable to receive an infusion may initiate weekly injections of subcutaneous Orencia without an intravenous loading dose. Patients transitioning from Orencia IV therapy to SC administration should administer the first SC dose instead of the next scheduled IV dose.

Orencia SC demonstrated similar efficacy (non-inferior for ACR 20 responses at 6 months) and safety to Orencia IV in a large non-inferiority trial. Concurrent therapy with Orencia and a biologic DMARD is not recommended. In controlled clinical trials, patients receiving concomitant Orencia and TNF antagonist therapy experienced more infections (63%) and serious infections (4.4%) compared to patients treated with only TNF antagonists (43% and 0.8%, respectively), without an important enhancement of efficacy. In the cumulative clinical trial program for IV, serious infections were 3% in Orencia vs. 1.9% in placebo, while malignancies were 1.3% in Orencia vs. 1.1% in placebo.

“Physicians now have a new option of a non-anti-TNF, with a different mechanism of action, when administering a biologic in a subcutaneous formulation,” said Mark C. Genovese, MD, professor of medicine and co-chief, Division of Immunology and Rheumatology, Stanford University Medical Center, and lead investigator of the registrational study supporting the approval. “The Orencia subcutaneous formulation demonstrated efficacy and safety consistent with the IV formulation. This choice is important for both patients and physicians when managing moderate to severe RA.”

The Orencia SC development program is composed of 4 clinical trials which studied nearly 2,000 patients. The phase 3 comparative trial studied 1,457 patients, making it the single largest phase 3 registrational trial of biologics in RA patients. The other 3 studies primarily evaluated safety and immunogenicity in 3 clinical scenarios: patients receiving Orencia as a monotherapy, patients withdrawn from and re-introduced to Orencia SC therapy and patients switching from Orencia IV to Orencia SC therapy.

ACQUIRE (Abatacept Comparison of Sub(Qu)cutaneous vs. Intravenous in Inadequate Responders to MethotrexatE), the phase 3 registrational trial, was a randomized, double-blind, double-dummy, multinational study. The primary end point of ACQUIRE was to determine non-inferiority of Orencia SC plus methotrexate (MTX) to Orencia IV plus MTX by difference in ACR 20 response at 6 months. The study included 1,457 patients with moderately to severely active RA, most of whom had an inadequate response to MTX. Patients were randomly assigned to weekly injections of a 1-mL solution containing a 125-mg dose of Orencia SC plus MTX, following a single IV loading dose (approximately 10 mg/kg) on Day 1, or Orencia IV (approximately 10 mg/kg) plus MTX on days 1, 15, 29, and every 4 weeks thereafter, for 6 months.

Orencia SC has not been studied in pediatric patients. Orencia should not be administered concomitantly with TNF antagonists. It is not recommended for use concomitantly with other biologic RA therapy, such as anakinra.

Orencia SC will be commercially available in the United States in September 2011.