FDA Panel Says No to Canakinumab for Gout Attacks

Fran Lowry

June 21, 2011

June 21, 2011 — The US Food and Drug Administration’s Arthritis Advisory Committee has voted against approval of the injectable biologic canakinumab (Ilaris, Novartis) for the treatment of acute gout flares in patients who do not respond to nonsteroidal anti-inflammatory drugs (NSAIDs) or colchicine, saying that it had too many concerns about safety.

The 12-member panel agreed that canakinumab was effective but voted a unanimous "no" when asked if its safety profile was sufficient to support approval for gouty arthritis in patients who do not respond to currently available treatments.

Panel members were equally unconvinced that canakinumab extended the time to the next gout flare and reduced the frequency of subsequent attacks, as the sponsor claimed.

Overall, the panel thought that canakinumab was just too risky to treat a condition that was very painful but not life-threatening. Infection, cardiovascular and renal function risks, and worries about the pharmacokinetics in older patients headed the list of safety concerns.

Sponsor’s Patients Not Representative of the 'Real World'

David Felson, MD, MPH, from Boston University School of Medicine, Boston Medical Center, in Massachusetts, said he found the safety issues very concerning.

"Many of the patients I see are not representative of the patients that were in the sponsor's study. Mine are older and often have other comorbidities and renal dysfunction, and are at high risk of infection," he said. "We’re in a situation where we don't have a life-threatening disease, and yet we’re giving therapy that in many cases might be life-threatening and I’m nervous about that."

Despite the negative votes, the panel agreed that there is a serious need for alternative treatment for patients who do not respond to current therapies for painful gout flares.

"Having taken care of many of these patients, I really believe there is an unmet need for people who have problems with NSAIDs or colchicine. This happens on a daily basis in our clinics. We need something for these patients," said Ted R. Mikuls, MD, from the University of Nebraska Medical Center in Omaha.

Allan Gibofsky, MD, JD, from Cornell University Medical College, New York, NY, agreed.

"Given the dramatic problems that occur in this population of patients who really do not have alternatives available to them...in that niche population, I think this drug has demonstrated efficacy," Dr. Gibofsky said.

Follow-up Time Too Short

Committee chair Katherine O'Neil, MD, from the University of Oklahoma College of Medicine, Oklahoma City, thought the 43 participants who were given repeated doses of canakinumab made up too small a sample and that the follow-up time of 6 months was too short. "We have not met the burden of proof of showing that this is a safe drug for that population," she said.

Lenore Buckley, MD, MPH, from Virginia Commonwealth University School of Medicine in Richmond, said more data are needed on patients with comorbid conditions that predispose to infection, such as chronic kidney disease; those with diabetes; transplant recipients; and patients with conditions such as psoriasis who are receiving methotrexate.

"There is a huge population of patients who would be candidates for this drug who are already immunosuppressed, and we don’t know the effect of giving them additional immunosuppression," she noted.

FDA Arthritis Advisory Committee. Hyattsville, Maryland, June 21, 2011.

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