Bristol-Myers Squibb Company (NYSE: BMY) today announced 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 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. ORENCIA should not be administered concomitantly with TNF antagonists. ORENCIA is not recommended for use concomitantly with other biologic RA therapy, such as anakinra.
“Delivering medicines that meet the needs of patients and physicians is core to Bristol-Myers Squibb's mission and commitment”
ORENCIA is the first and only biologic for the treatment of RA available in self-injectable (SC) and also an intravenous (IV) infusion formulation. 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 intravenous therapy to subcutaneous administration should administer the first subcutaneous dose instead of the next scheduled intravenous 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® (abatacept) 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, 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. "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 four 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 three studies primarily evaluated safety and immunogenicity in three 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.
"Delivering medicines that meet the needs of patients and physicians is core to Bristol-Myers Squibb's mission and commitment," said Anthony Hooper, senior vice president, commercial operations, and president U.S., Japan and Intercontinental, Bristol-Myers Squibb. "The continued development of ORENCIA exemplifies our company's focus on areas of serious diseases and biologics drug development."
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 endpoint 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 randomized 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.
Comparable ACR 20 response rates of 76% (95% confidence interval [CI]: -4.2, 4.8 [based on prespecified margin for non-inferiority of -7.5%] for the SC group) were seen in both groups of patients receiving SC injections plus MTX or IV infusions plus MTX at month 6. ACR 50 and ACR 70 responses were comparable between ORENCIA SC and IV as were improvements in all patient-reported outcomes studied - pain, physical function and global assessment of disease activity for ORENCIA SC and IV at 6 months. High retention rates were seen at month 6: 94% of patients receiving SC injections plus MTX and 94% of patients receiving ORENCIA IV plus MTX remained in the study.
The safety experience and immunogenicity for ORENCIA SC was consistent with the profile for IV therapy. Local subcutaneous injection-site reactions occurred in 2.6% of patients receiving ORENCIA SC plus MTX and 2.5% of patients receiving SC placebo plus MTX. All injection-site reactions (including hematoma, pruritus and erythema) were mild (83%) to moderate (17%) and none necessitated drug discontinuation. Immunogenicity was observed in 1.1% and 2.3% of ORENCIA® (abatacept) SC plus MTX and ORENCIA IV plus MTX patients, respectively. There was no correlation of immunogenicity with effects on pharmacokinetics, efficacy or safety.
The most common adverse events reported in greater than 5% of patients in either the SC or IV ORENCIA groups were headache, nasopharyngitis, upper respiratory tract infection, diarrhea and nausea. Serious adverse events occurred in 4.2% of patients in the ORENCIA SC plus MTX group and 4.9% of patients in the ORENCIA IV plus MTX group. Of those, serious infections occurred in 0.7% of patients in the ORENCIA SC plus MTX group versus 1.4% of patients in the ORENCIA IV plus MTX group while malignancies occurred in 0.4% of patients in the ORENCIA SC plus MTX group versus 0.7% of patients in the ORENCIA IV plus MTX group.
ORENCIA SC will be commercially available in the U.S. in September 2011.
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