FDA Approves Subcutaneous Formulation Of ORENCIA (Abatacept) For Adults With Moderate To Severe Rheumatoid Arthritis

Editor's Choice
Main Category: Arthritis / Rheumatology
Also Included In: Regulatory Affairs / Drug Approvals
Article Date: 03 Aug 2011 - 7:00 PDT


Bristol-Myers Squibb Company announced today that the U.S. Food and Drug Administration (FDA) has approved a subcutaneous (SC) formulation of ORENCIA® (abatacept) for the treatment of adults with moderate to severe rheumatoid arthritis (RA).

ORENCIA is a medication aimed at reducing signs and symptoms, inducing major clinical response, control progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis.

ORENCIA can be administered as monotherapy or alongisde disease-modifying antirheumatic drugs (DMARDs) other than tumor necrosis factor (TNF) antagonists. It should not be used together with TNF antagonists and is not recommended concomitantly with other biologic RA therapy, such as anakinra.

As the first and only biologic RA treatment available as a self-injectable (SC) and as intravenous (IV) infusion, the approval of abatacept offers physicians a wider choice for treating patients, as the majority of RA patients start their therapy with a biologic SC injection.

The new SC formulation consists of a fixed 125 mg dose given weekly through injection under the patient's skin, followed by a single IV load dose of approximately 10 mg/kg. Those patients unable to receive infusions may receive weekly injections of subcutaneous ORENCIA without an intravenous loading dose. Patients changing from ORENCIA intravenous therapy to subcutaneous administration should take the first subcutaneous dose instead of the next scheduled intravenous dose.

In a large non-inferiority trial, ORENCIA SC showed similar effectiveness (non-inferior for ACR 20 responses at 6 months) and safety to ORENCIA IV. It is not recommended to use ORENCIA and a biologic DMARD simultaneously. Controlled clinical trials revealed, that patients who received ORENCIA and TNF antagonist simultaneously, developed 63% more infections and 4.4% more serious infections compared to patients treated with only TNF antagonists (43% and 0.8%, respectively), without an increase in efficacy. The cumulative clinical trial program for IV revealed that serious infections were 3% in ORENCIA® (abatacept) vs. 1.9% in placebo while malignancies were 1.3% in ORENCIA vs. 1.1% in placebo.

Mark C. Genovese, M.D., 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 said:

"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. 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 constituted four clinical trials, studying nearly 2,000 patients. Phase 3 of a comparative trial studied 1,457 patients, making it the single largest Phase 3 registrational trial of biologics in RA patients. The remaining three studies primarily evaluated safety and immunogenicity in three different 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.

Anthony Hooper, senior vice president of commercial operations, and president of U.S. Japan and Intercontinental at Bristol-Myers Squibb stated:

"Delivering medicines that meet the needs of patients and physicians is core to Bristol-Myers Squibb's mission and commitment. The continued development of ORENCIA exemplifies our company's focus on areas of serious diseases and biologics drug development."

Phase 3 of the registrational trial for ACQUIRE (Abatacept Comparison of Sub(Qu)cutaneous vs. Intravenous in Inadequate Responders to MethotrexatE) was a randomized, double-blind, double-dummy, multinational study. The primary goal of ACQUIRE was to evaluate non-inferiority of ORENCIA SC plus methotrexate (MTX) to ORENCIA IV plus MTX by difference in ACR 20 response at 6 months. The study consisted of 1,457 patients with moderately to severely active RA, of which most had an inadequate response to MTX. Patients were randomized to weekly injections of a 1 mL solution containing a 125 mg dose of ORENCIA SC plus MTX, followed by 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.

Both patient groups receiving SC injections plus MTX or IV infusions plus MTX at month 6 had a comparable ACR 20 response rate of 76% (95% confidence interval [CI]: -4.2, 4.8 [based on pre-specified margin for non-inferiority of -7.5%] for the SC group). ACR 50 and ACR 70 responses between ORENCIA SC and IV at 6 months were comparable as well as improvements in all patient-reported outcomes - pain, physical function and global assessment of disease activity. At month 6, high retention rates were seen in 94% of patients remaining in the study who received SC injections plus MTX and 94% of patients receiving ORENCIA IV plus MTX.

ORENCIA SC was consistent with ORIANA IV in terms of safety and immunogenicity. 2.6 percent of patients who received ORENCIA SC plus MTX showed local subcutaneous reactions to the injection site compared to 2.5 percent of patients who received SC placebo plus MTX. All injection-site reactions (including hematoma, pruritus and erythema) were mild (83%) to moderate (17%) and none required termination of drug treatment. Immunogenicity was observed in 1.1% and 2.3% of ORENCIA® (abatacept) SC plus MTX and ORENCIA IV plus MTX patients, respectively. No correlation of immunogenicity with effects on pharmacokinetics, efficacy or safety was detected.

The most common adverse effects discovered in more than 5% of patients in either the SC or IV ORENCIA groups were headache, nasopharyngitis, upper respiratory tract infection, diarrhea and nausea. 4.2% of patients in the ORENCIA SC plus MTX group and 4.9% of patients in the ORENCIA IV plus MTX group developed serious adverse effects. Serious infections developed in 0.7% of patients in the ORENCIA SC plus MTX group versus 1.4% of patients in the ORENCIA IV plus MTX group whilst malignancies appeared in 0.4% of patients in the ORENCIA SC plus MTX group versus 0.7% of patients in the ORENCIA IV plus MTX group.

Written by Grace Rattue


Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

• Additional
• References
• Citations