FDA approves subcutaneous Actemra for RA patients

The FDA has approved a subcutaneous formulation of tocilizumab for treating adults with moderately to severely active rheumatoid arthritis who did not have adequate response to one or more disease-modifying antirheumatic drugs, Genentech has announced.

Tocilizumab (Actemra), a humanized interleukin-6 receptor-antagonist monoclonal antibody, previously had received FDA approval for intravenous administration. The subcutaneous (SC) formulation may be used as single-agent therapy or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs), according to a press release. The pre-filled syringe (PFS) injection formula for Actemra will be available in November, Genentech reported.

The FDA has recommended dosages of Actemra SC of 162 mg every 2 weeks for patients weighing less than 220 pounds and 162 mg weekly for patients weighing 220 pounds or more.

“Because some patients prefer a subcutaneous injection, it is important for physicians to have this new option,” Alan J. Kivitz, MD, FACR, president of the Altoona Center for Clinical Research, Duncansville, Pa., said in the release. “In clinical trials, Actemra was shown to be effective and have a consistent safety profile — with the exception of injection-site reactions for the subcutaneous formulation — when administered either intravenously or subcutaneously and may be used with or without methotrexate.”

The FDA’s approval was based on results from two phase 3 clinical trials.

Researchers studied 1,262 patients with moderately to severely active rheumatoid arthritis (RA) in a 24-week randomized, double blind, multicenter study (SUMMACTA). The SC formulation of 162 mg tocilizumab weekly plus DMARDs showed comparable efficacy to 8 mg/kg of tocilizumab given intravenously every 4 weeks plus DMARDs in RA patients who had inadequate response to anti-tumor necrosis factor therapy. Safety analysis showed that both patient groups had comparable adverse event profiles, except for the SC injection-site reactions.

In a second study (BREVACTA), researchers randomly assigned 656 patients with RA who had inadequate response to DMARD therapy in a 2:1 ratio to receive tocilizumab SC every 2 weeks administered with a PFS or placebo SC every 2 weeks with a PFS. Background DMARD therapy was continued for all patients.

Patients who received Actemra were significantly more likely to have achieved ACR20 response than those given placebo at 24 weeks (61% vs. 36%, respectively), the release said.

Besides SC injection-site reactions, no new clinically meaningful safety signals for tocilizumab were observed. Upper respiratory tract infections, headache, hypertension and injection-site reactions were common side effects of tocilizumab, Genentech reported. Serious side effects included stomach tears, changes in blood test results, an increased risk for certain cancers, hepatitis B infection, allergic reactions, including death, and nervous system problems, according to the release.