FDA Approves Subcutaneous Form of RA Biologic

A subcutaneous formulation of abatacept that patients can inject themselves has been approved by the Food and Drug Administration, according to a statement issued July 29 by the manufacturer, Bristol-Myers Squibb.

Like the intravenous formulation, this preparation is approved for treatment of adults with moderate to severe rheumatoid arthritis and can be used as monotherapy or in combination with disease-modifying antirheumatic drugs, other than tumor necrosis factor antagonists. Intravenous abatacept is also approved as a treatment for children aged 6 years and older who have moderately to severely active polyarticular juvenile idiopathic arthritis. The subcutaneous formulation has not been studied in pediatric patients, according to the Bristol-Myers Squibb statement.

The IV formulation of abatacept, a selective T-cell costimulator modulator marketed as Orencia, was approved in 2005.

The approved dosing of subcutaneous abatacept is a fixed 125 mg dose, administered once a week after a single IV loading dose of approximately 10 mg/kg. Patients who are not able to receive an infusion may start weekly subcutaneous injections of abatacept, without the IV loading dose. Those switching from IV abatacept to subcutaneous therapy should administer the first subcutaneous dose instead of the next IV dose, according to the revised prescribing information.

The efficacy of subcutaneous therapy was similar to IV therapy in the ACQUIRE (Abatacept Comparison of Sub(Qu)cutaneous vs. Intravenous in Inadequate Responders to Methotrexate) study of almost 1,500 patients with moderately to severely active RA, most of whom had not had adequate responses to methotrexate alone, according to Bristol-Myers Squibb. The study, a phase III noninferiority study, compared treatment with subcutaneous abatacept plus methotrexate (after a single IV loading dose of about 10 mg/kg of abatacept) to IV abatacept plus methotrexate on days 1, 15, 29, and then every 4 weeks.

At 6 months, 76% of patients in both groups had achieved an ACR 20 response. ACR 50 and ACR 70 responses, as well as pain, physical, function, and global assessments for disease activity – and the safety profile –were also comparable between the two groups. Side effects included headache, nasopharyngitis, and upper respiratory tract infections; 2.6% of those who received the subcutaneous injections had injection-site reactions.

The rate of serious adverse events was 4.2% among those on subcutaneous (SC) abatacept and 4.9% of those in the IV group, and included serious infections (0.7% of those on subcutaneous dosing and 1.4% of those on the IV dose) and malignancies (under 1% in both groups).

Immunogenicity was seen in 1.1% of those on SC treatment and 2.3% of those on IV therapy, but this did not correlate with effects on pharmacokinetics, efficacy, or safety, the statement said.

The SC formulation will be marketed as Orencia SC and will be available in September, according to Bristol-Myers Squibb. The price is not yet available, a company spokesperson said.