The FDA has delayed approval for Actemra pending submission of extra product manufacturing and product label information by the drug manufacturer, Roche Holding AG. This comes a week after requiring ordering label changes for Rituxan, which is manufactured by Genentech and Biogen Idec. Roche is a majority shareholder of Genentech. Genentech also partners with Chugai in Japan to make Actemra.
FDA approval of Actemra is extremely important to the company(s) because it is a novel drug here in the U.S. that will compete both with its own Rituxan and against other manufacturers that make the TNF-Inhibitors (such as Humira and Enbrel). It is projected to make a billion dollars for the company once it is approved and on the market here in the U.S. In its press release, Roche was careful to point out that the FDA has not requested any new clinical studies related to the efficacy or safety of Actemra. Roche also stated that it will work to comply with FDA requests and that once it submits this information, it "does not foresee any issues that would impact the quality, availability and supply of ACTEMRA in the U.S."
Actemra is an injectible drug that inhibits the action of RA by blocking IL-6 proteins that are involved in increasing inflammation in the body. Once approved, it will be indicated to treat people with moderate to severe RA. Rituxan is given by infusion and works to reduce inflammation and inhibit the immune system by killing off B-cells. It is often given in conjunction with methotrexate and is indicated for people with moderate to severe RA that have not responded to TNF inhibitors.
Roche is a co-developer of Actemra with Chugai Pharmaceuticals Co. The drug has been on the market in Japan since June 2005, originally as a treatment for Castleman's disease. In April 2008, the Japanese government also approved the drug for rheumatoid arthritis, juvenile idiopathic arthritis and systemic-onset juvenile idiopathic arthritis. Roche filed the application for FDA approval in November 2007. On July 29, 2008, the Arthritis Advisory Committee of the FDA voted 10-1 to recommend approval of Actemra.
My take: So maybe this isn't a big deal. The clinical trials over the past several years for Actemra have shown positive results either by itself or in combination with methotrexate. Similar to the other immune system inhibitors like the TNF inhibitors and Rituxan, serious adverse reactions have been reported for Actemra, including serious infections, gastrointestinal perforations and hypersensitivity reactions including anaphylaxis. It also carries an increased risk of malignancies. The most common adverse reactions reported in clinical studies were upper respiratory tract infection, nasopharyngitis, headache, hypertension and increased ALT (liver enzymes). Patients also showed increases in lipids (total cholesterol, LDL, HDL, triglycerides) and decreases in neutrophils and platelets.
The request for more information and the final product label may be a function of the increased pressure on the FDA to alter the approval process while it tries to verify that drugs are safe and effective and that marketing materials and product labels are straightforward and include all necessary or relevant information.
Published On: September 19, 2008