FDA Issues Complete Response Letter to Roche for ACTEMRA® (tocilizumab) Biologics License Application

--No New Clinical Studies Requested--

Roche today announced that the U.S. Food and Drug Administration (FDA) has issued a complete response letter for the Biologics License Application (BLA) for ACTEMRA® (tocilizumab), the first interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody studied for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA).

The FDA has not requested any new clinical studies surrounding the efficacy or safety of ACTEMRA as a prerequisite for approval. The FDA has requested additional documentation related to the manufacturing of ACTEMRA and certain other outstanding components, such as final labeling. Roche is committed to working with the FDA to promptly address any outstanding matters. Upon satisfactory completion of the FDA’s requests and an approved label, Roche does not foresee any issues that would impact the quality, availability and supply of ACTEMRA in the U.S.

“Roche is committed to working with the FDA to make this important new therapy available to RA patients as soon as possible,” said George Abercrombie, CEO and president of Roche. “We will continue to work closely with the agency to address its questions and define the path forward for ACTEMRA. We are confident that we will be able to resolve any outstanding matters in the near future.”

Roche submitted the BLA for ACTEMRA to the agency on November 18, 2007. The BLA for ACTEMRA is based on the results of an extensive multi-national clinical development program, which included more than 4,000 patients in 41 countries, including the U.S. These studies demonstrated that treatment with ACTEMRA – alone or combination with methotrexate or other DMARDs (disease modifying anti-rheumatic drugs) – significantly reduced RA signs and symptoms, regardless of previous therapy or disease severity, compared with DMARDs alone. On July 29, 2008, the Arthritis Advisory Committee of the FDA voted 10-1 to recommend approval of ACTEMRA.

About ACTEMRA (tocilizumab)
ACTEMRA is the first humanized interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody for RA. Studies demonstrate that reducing the activity of IL-6, one of several key cytokines involved in the inflammatory process, relieves both inflammation of the joints and certain systemic effects of RA. The extensive clinical development program conducted by Roche includes five clinical studies and has enrolled more than 4,000 patients in 41 countries, including the United States. Four Phase III studies are completed and have reported meeting their primary endpoints. The fifth Phase III study, the LITHE trial evaluating ACTEMRA in RA is an ongoing two-year study, which is expected to report complete data evaluating the effects of ACTEMRA on the inhibition of structural joint damage in 2009. ACTEMRA is under review in the United States and Europe.

ACTEMRA is part of a co-development agreement with Chugai Pharmaceuticals Co. In June 2005, ACTEMRA was launched by Chugai in Japan as a therapy for Castleman’s disease; in April 2008, additional indications for rheumatoid arthritis, juvenile idiopathic arthritis and systemic-onset juvenile idiopathic arthritis were also approved in Japan.

The serious adverse reactions reported in ACTEMRA clinical studies include serious infections, gastrointestinal perforations and hypersensitivity reactions including anaphylaxis. The most common adverse reactions reported in clinical studies were upper respiratory tract infection, nasopharyngitis, headache, hypertension and increased ALT. Increases in liver enzymes (ALT and AST) were seen in some patients; these increases were generally mild and reversible, with no evidence of hepatic injuries. Laboratory changes, including increases in lipids (total cholesterol, LDL, HDL, triglycerides) and decreases in neutrophils and platelets, were seen in some patients without association with clinical outcomes. Treatments that suppress the immune system, such as ACTEMRA, may cause an increase in the risk of malignancies.