New Biologic Drug for RA Earns FDA Committee Approval
July 30--The Arthritis Advisory Committee of the Food and Drug Administration’s Center for Drug Evaluation and Research voted 10-1 on Tuesday to recommend approval for a new biologic drug to treat rheumatoid arthritis in adults.
Tocilizumab, brand-named Actemra, is the first medication to block a protein called interleukin-6 (IL-6), which triggers inflammation.
Yesterday’s vote was a significant step toward making this drug available in the United States. The FDA usually follows the recommendation of its advisory committees when deciding whether to allow new pharmaceuticals to be marketed to the public. The agency is expected to issue a final decision on tocilizumab this fall.
The lone dissenter on the committee was the consumer representative, Diane Aronson. Aronson said she was excited about the possibilities of the drug but is "still concerned about the safety problems and want more information about the long- term impact on the liver."
Arthritis Today spoke with David Felson, M. D., MPH, a professor of medicine and epidemiology at Boston University School of Medicine. Dr. Felson was a temporary voting member of the Arthritis Advisory Committee during its review of tocilizumab.
– Brenda Goodman
AT: You voted to recommend approval of tocilizumab. Can you discuss the thinking behind your decision?
Dr. David Felson: I think it’s a pretty effective treatment overall, based on the company’s presentation yesterday. I thought the toxicity issues were similar to what we’ve seen for the other biologics. But this drug does have some side effects, and at this point in the development of the drug, it’s impossible know if the little signals that you see are scary and dangerous or if they are manageable and unlikely to cause significant harm. But in the end, the benefits seemed to outweigh the risks.
AT: Many people with RA are hoping this drug might succeed where other treatments have failed.
Dr. Felson: It showed efficacy in people who had even failed TNF-inhibitors, which is this new subpopulation that we’re encountering that we didn’t expect. This is a group, that even though we put them on the best medicine available, just isn’t doing very well. And this drug seemed to help some of them.
AT: Let’s talk about some of the major side effects. The clinical trials showed that tocilizumab raised levels of LDL cholesterol.
Dr. Felson: That’s the thing that concerns me the most. It does look like it’s different from most of the other treatments that we use for rheumatoid arthritis. The other biologics raise HDL cholesterol, the “good” cholesterol. This raises LDL, the “bad” cholesterol, so that’s bad. The overall percentage of [cardiovascular] events with patients with RA is just not known. There’s just not enough data to know if the lipid change would be great enough to put them at risk for heart attack or stroke.
RA patients tend to be older patients and their major cause of mortality is cardiovascular events, so we’re not looking at a low risk population. We’re looking at a high-risk population, so that’s bad.
AT: Study participants who took tocilizumab had a higher risk of serious infections compared to study participants who were treated with methotrexate alone or with a combination of a disease modifying anti-rheumatic drug and a placebo.
Dr. Felson: Yes. Pneumonia and cellulitis [a potentially serious bacterial skin infection] were the most commonly occurring serious infections, but all immunosuppressant drugs can increase the risk of infection, so this was about the same as other options out there.
AT: The data also showed a small number of study participants, 15 out of 4700, according to data compiled by Roche, the manufacturer, suffered gastrointestinal perforations.
Dr. Felson: I didn’t know what to make of that. Every patient with perforations was also on NSAIDs [non-steroidal anti-inflammatory drugs], which are known to cause upper GI perforations. There was no way to tell whether this drug added to that risk. But GI perforations, where an ulcer becomes so bad that it eats through the wall of the stomach or the intestine, these are life threatening. It’s not a trivial matter.
AT: How do you think doctors will begin to use tocilizumab in adult patients with RA?
Dr. Felson: It’s going to be used late among all of these different options, methotrexate, TNF-inhibitors, then somewhere after those, this. Given its toxicity profile it should not be used early.
Dr. Felson said he has not received funding from the drug’s manufacturer, Roche.
To read more about biologic drugs, including their benefits and risks, check out Arthritis Today's Drug Guide.
