Genentech, Biogen Idec: FDA approves Rituxan for rheumatoid arthritis

By E. Janene Geiss

Philadelphia, March 1 - Genentech Inc. and Biogen Idec Inc. announced late Tuesday that the Food and Drug Administration has approved, following priority review, the therapeutic antibody Rituxan (rituximab) in combination with methotrexate to reduce signs and symptoms in adult patients with moderately-to-severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor antagonist therapies.

Rituxan is the first treatment for rheumatoid arthritis that selectively targets immune cells known as CD20-positive B-cells. Through this unique mechanism of action, Rituxan may affect multiple pathways by which B-cells are believed to contribute to the initiation and development of rheumatoid arthritis, according to a company news release.

"The FDA approval of Rituxan for [rheumatoid arthritis] provides an important new treatment approach for patients who do not respond adequately to TNF antagonist therapy," Stephen Paget, chairman, professor of medicine and physician-in-chief at the department of medicine, division of rheumatology, at the Hospital for Special Surgery in New York, said in the release.

"In clinical trials, Rituxan demonstrated significant improvement in joint pain, inflammation and physical function from a single course of therapy in this difficult-to-treat patient population," Paget added.

The FDA based its approval decision for Rituxan for rheumatoid arthritis on data from three randomized, double-blind, placebo-controlled studies of patients with active rheumatoid arthritis.

Results of the pivotal phase 3 trial known as Reflex showed that a significantly greater proportion of patients who received a single treatment course of two infusions of Rituxan (1,000 mg on days one and 15) with a stable dose of methotrexate achieved American College of Rheumatology 20, 50 and 70 response rates compared to patients who received a placebo and methotrexate.

The study included patients with active rheumatoid arthritis who had an inadequate response or were intolerant to prior treatment with one or more TNF antagonist therapies and current methotrexate therapy, officials said.

At 24 weeks, patients receiving Rituxan displayed clinically and statistically significant improvements in rheumatoid arthritis signs and symptoms, including pain and disability.

In patients receiving Rituxan, 51% achieved ACR 20, the primary endpoint of the study, versus 18% of placebo patients; 27% achieved ACR 50, versus 5% of placebo patients; and 12% achieved ACR 70, versus 1% of placebo patients, officials said.

Rituxan also was shown to reduce biologic markers of inflammation, officials added.

In the study, the most frequently reported adverse events that occurred with Rituxan were primarily infusion-associated. Serious adverse events occurred in 7% of patients receiving Rituxan and methotrexate compared to 10% in patients receiving a placebo and methotrexate.

Less than 1% of acute infusion reactions were serious. The incidence of serious infections was 2% in Rituxan-treated patients and 1% in placebo-treated patients.

The companies said they are committed to monitoring long-term safety of the drug.

"The FDA approval of Rituxan for [rheumatoid arthritis] marks an important milestone in our ongoing efforts to advance the understanding of B-cell-mediated autoimmune diseases," Hal Barron, Genentech's senior vice president, development and chief medical officer, said in the release.

"This milestone, coupled with the additional new indication for Rituxan in diffuse large B-cell lymphoma, further establishes the companies at the forefront of novel B-cell research," Barron added.

Rheumatoid arthritis is a debilitating autoimmune disease that affects more than 2 million Americans and hinders the daily activities of sufferers.

Rituxan is a therapeutic antibody that targets and selectively depletes CD20-positive B-cells without targeting stem cells or existing plasma cells. In patients with rheumatoid arthritis, Rituxan is given as two 1,000 mg IV infusions separated by two weeks, in combination with methotrexate. It is recommended to administer the steroid methylprednisolone 100 mg IV 30 minutes prior to each infusion.

In addition to rheumatoid arthritis, Rituxan is being studied in other autoimmune diseases with significant unmet medical needs, including systemic lupus erythematosus, lupus nephritis, multiple sclerosis and ANCA-associated vasculitis.

Rituxan, discovered by Biogen Idec, received FDA approval in November 1997 for the treatment of relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma.

It also was approved in the European Union under the trade name MabThera in June 1998.

In addition, Rituxan received FDA approval in February for the treatment of DLBCL in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or other anthracycline-based chemotherapy regimens in previously untreated patients.

Genentech and Biogen Idec co-market Rituxan in the United States, and Roche markets MabThera in the rest of the world, except Japan, where Rituxan is co-marketed by Chugai and Zenyaku Kogyo Co. Ltd.

Rituxan is the top-selling oncology therapeutic in the United States with more than 730,000 patient exposures worldwide, officials said.

Genentech is a South San Francisco biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for significant unmet medical needs.

Biogen Idec is a Cambridge, Mass., biotechnology company that develops, manufactures and commercializes new therapies for oncology, neurology and immunology.

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