FDA Deems Drug Unsafe for Gout Treatment

June 22, 2011

The Food and Drug Administration has deemed canakinumab unsafe for consumers, despite its effectiveness for treating acute flares of gout.

The Arthritis Advisory Committee, a sector of the United States Food and Drug Administration (FDA), has deemed the biologic drug canakinumab (Ilaris) unsafe for consumers, despite its effectiveness for treating acute flares of gout.

The FDA reported that it was most apprehensive about safety issues observed in the drug clinical trials, such as increased rates of infections, high triglyceride levels, and elevated uric acid levels in blood.

Manufactured by Novartis Pharmaceuticals, canakinumab is a monoclonal antibody targeting the interleukin-1-beta protein. It has gained approval previously for two rare inflammatory diseases—familial cold autoinflammatory syndrome and Muckle-Wells syndrome. For gouty arthritis, canakinumab’s intended purpose is primarily symptomatic relief, not modification of the underlying disease.

The twelve member panel of the Arthritis Advisory Committee unanimously voted that the safety of the drug was not up to acceptable standards, but the panel also agreed by an eleven to one vote that the drug’s effectiveness was not in question, as the data from the drug trials showed that symptomatic relief was genuine in participants.

The members agreed eight to four that the drug reduced the frequency of consequent attacks.

"I found the safety issues to be overwhelmingly concerning," said David Felson, MD, a professor of medicine at Boston University and a member of the advisory panel.

Several studies reported that canakinumab was discovered to reduce pain associated with acute gout attacks in clinical trial participants; it also was reported that the drug decreased the frequency of attacks in patients with a history of six to seven flares per year by roughly 60% to 70%.

Unfortunately, of the 691 participants treated with canakinumab in the clinical trials, severe infections were observed in 1.7% of them while none were observed in the 400 control participants. The rate with canakinumab relative to drug exposure was six serious infections per 100 patient-years.

"Given that [canakinumab] is expected to provide primarily a symptomatic benefit, is the risk of infection still outweighed by the clinical benefits?" queried the FDA staff in a briefing document for the panel.

Rises in triglycerides occurred in numerous patients who received the 150-mg dose of canakinumab; roughly 40% of these patients displayed levels above the normal range, and 10% had levels 2.5 times the upper limit of what is normal.

Increases in serum uric acid were also observed in patients receiving more than 2 mg; these increases affected 36% of patients in one trial and 27% in another.

The FDA also suggested that Novartis's recommended dosing recommendation—a single 150-mg subcutaneous injection followed by additional doses "on demand"—would be more appropriately regarded for chronic treatment instead of a therapy for acute attacks.

Despite these inquiries and roadblocks, however, Novartis’s spirits do not seem too dampened. Trevor Mundel, head of development at Novartis Pharmaceuticals, reported that the company is optimistic because of the committee's "enthusiasm and robust discussion,” and he continued to say that they “will work closely with the FDA to identify the right patient population who will benefit from this therapy".