January 23, 2009 — The European Commission has approved Roche's first-in-class therapeutic tocilizumab (RoACTEMRA) for the treatment of moderate-to-severe rheumatoid arthritis (RA). Tocilizumab is the first interleukin 6 (IL-6) receptor–inhibiting monoclonal antibody developed for the treatment of RA. It is indicated in combination with methotrexate (MTX) for the treatment of adult patients with moderate-to-severe RA who have either responded inadequately to or were intolerant to therapy with other disease-modifying antirheumatic drugs (DMARDs) or tumor necrosis factor-alpha (TNF-alpha) antagonists. Reducing IL-6 reportedly relieves inflammation of the joints and some systemic effects of RA.
The European Commission approved tocilizumab on the basis of results from several phase 3 studies, including the Actemra versus Methotrexate double-Blind Investigative Trial In mONotherapy (AMBITION) and the RheumAtoiD ArthritIs Study in Anti-TNF FailurEs (RADIATE), demonstrating that treatment with tocilizumab — either alone or in combination with MTX or other DMARDs — significantly reduced RA signs and symptoms compared with treatment with current DMARDs alone, regardless of previous therapy or disease severity.
The AMBITION study showed for the first time that treatment with a single biologic agent was superior to MTX for the treatment of RA at 6 months. The RADIATE trial illustrated that 30% of patients who received tocilizumab in combination with MTX achieved disease remission compared with 1.6% of patients who received MTX alone. The RADIATE results are particularly promising for RA patients who have failed to achieve adequate pain and symptom relief with anti-TNF-alpha therapies, according to the study's principal investigator, Paul Emory, MD, professor of rheumatology, University of Leeds, United Kingdom.
Tocilizumab, known as Actemra outside of the European Union, was previously approved in Japan, India, and Switzerland. In July 2008, the US Food and Drug Administration (FDA) Arthritis Advisory Committee recommended approval of tocilizumab. Since then, the FDA has defined several criteria with which Roche must comply. Among these are a Risk Evaluation and Mitigation Strategy plan aimed at ensuring that healthcare professionals prescribe and administer tocilizumab correctly and that patients understand the potential benefits and risks associated with the medication. The FDA has also asked Roche for additional animal data to confirm that tocilizumab does not affect peri- and postnatal development and fertility, but it has not requested additional clinical studies. The FDA Office of Compliance has completed its evaluation of Roche's manufacturing facility in Japan and has indicated that it is acceptable for manufacturing the RA therapeutic.
A Roche spokesperson confirmed that the company is currently working to fulfill the FDA's requirements, and it anticipates submitting all data and materials necessary to satisfy the FDA's complete response requirements in the third quarter of this year.
Roche's clinical development of tocilizumab has included 5 phase 3 clinical studies and has enrolled more than 4000 patients in 41 countries. Four studies are complete, and the fifth is expected to report its final 2-year outcomes on inhibition of structural joint damage this year.
Serious adverse reactions reported in tocilizumab clinical studies include serious infections, gastrointestinal perforations, and hypersensitivity reactions including anaphylaxis. The most common adverse reactions reported were upper respiratory tract infection, nasopharyngitis, headache, hypertension, and mild and reversible increases in alanine aminotransferase enzymes.
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Cite this: Rochelle Nataloni . Tocilizumab Approved for Rheumatoid Arthritis in Europe - Medscape - Jan 23, 2009.