One year after asking the Roche group to submit additional data for its monoclonal antibody tocilizumab, the FDA has approved the biologic agent for the treatment of moderate to severe rheumatoid arthritis (see story).
Although the drug, to be marketed under the name Actemra, is entering a somewhat crowded biologics market—it is joining abatacept, adalimumab, anakinra, etanercept, infliximab, and rituximab —it is the first and so far only interleukin-6 (IL-6) receptor inhibitor to be approved for the indication, and clinicians are cautiously optimistic that it will improve the lives of patients who have not responded to therapy with methotrexate alone or in combination with other disease modifying antirheumatic drugs (DMARDS).
In fact, tocilizumab has been approved specifically for those adult patients who have failed methotrexate and one or more tumor necrosis factor antagonist, according to an announcement released today by the drug’s manufacturer, Roche Holding AG.
The FDA approval is a much-anticipated development, according to Dr. Larry Greenbaum, a rheumatologist in private practice in Indianapolis. “It’s very exciting. Actually, one of the drug representatives has been stopping by my office for the last year or two, dropping hints about this product, although the company has not been allowed to “detail” the drug before release. And of course, there have been many drug company ads creating a crescendo of drum beats before the official release date,” he said in an interview.
The novelty of tocilizumab lends to the excitement. “There are multiple anti-TNF medications currently, and the reps for those drugs are trying very hard to convince clinicians to choose one medication over another, even though they are probably more similar than different,” Dr. Greenbaum commented. As an IL-6 blocker, tocilizumab IS different, which is why the industry is buzzing, he noted.
The new-drug hype notwithstanding, there are still a number of questions to be answered before clinicians can consider the potential clinical impact of tocilizumab, according to Dr. Greenbaum. “The main questions for me are: Is this medication any safer or more dangerous than the current biologic drugs? Is this medication more or less affordable (or accessible) than the current biologics? Where does this medication belong in the treatment algorithm?
“Undoubtedly, the company is going to try and convince doctors to use this medication immediately after methotrexate failure, but they will first have to convince doctors (and insurers) that this strategy is warranted,” Dr. Greenbaum said.
Of particular concern are the side effects. Biologic agents are powerhouse drugs, and powerhouse drugs often have the potential for causing serious adverse effects. Among the serious tocilizumab-related adverse events that have been reported in pivotal clinical trials include infections that lead to hospitalization or death, including tuberculosis, bacterial, invasive fungal, viral and other infections; gastrointestinal perforations; hypersensitivity reactions; and cellulitis. In March 2009, Roche’s Chugai Pharmaceuticals reported that among nearly 5,000 rheumatoid arthritis patients in Japan who had been treated with tocilizumab between April 2008 and February 2009, 15 deaths occurred and the possibility of a link to the drug could not be denied, although the exact causes of the deaths were unknown, according to a press release issued by the company.
Some of the common side effects associated with tocilizumab include upper respiratory infections, including pneumonia, inflammation of the nose and throat, headache, high blood pressure, increased liver enzymes, increased cholesterol levels, neutrophil decreases, and platelet decreases, according to the company.
The drug’s approval comes with a Risk Evaluation and Mitigation Strategy (REMS), which includes a medication guide, communication plan, and timetable for submission of assessments. The drug itself will be available the week of January 18, 2010.
—Diana Mahoney (on Twitter @dmpm1)