FDA Panel Votes Against Biologic for Gouty Arthritis Flares

ADELPHI, MD. – A Food and Drug Administration advisory panel on June 21 voted 11-1 that the data on canakinumab did not support its approval as a treatment for gouty arthritis attacks, in patients who have not responded adequately to nonsteroidal anti-inflammatory drugs or colchicine.

Members of the FDA’s Arthritis Advisory Committee considered canakinumab a promising treatment, and all but one panelist agreed that the 150-mg subcutaneous dose that was studied in two phase III trials was shown to be effective in treating an attack of gouty arthritis in this population.

But, in another vote, the panel unanimously agreed that the safety profile of canakinumab did not support approval for this indication, because of concerns that included the lack of long-term safety data including the potential long-term risk of infections and the lack of data on the effects of recurrent treatment. (Only 43 patients in the studies had received three or more injections and most had been treated only once.)

The need for more data in likely patient candidates who are less healthy than those in the trials, such as those with advanced renal disease, was another concern cited by the panel. Several panelists also expressed concern that unless use was restricted in some way, canakinumab might be used to treat a broader population than described in the proposed indication.

Canakinumab (Ilaris), a monoclonal antibody that neutralizes interleukin-1beta, was approved in June 2009 for the treatment of a rare disorder, cryopyrin-associated periodic syndromes (CAPS). The new indication proposed by the manufacturer, Novartis Pharmaceuticals, is for the treatment of gouty arthritis attacks in patients who cannot obtain an adequate response with NSAIDs or colchicine.

The company described canakinumab as the first targeted anti-inflammatory treatment for gout, which could be used to treat about 6% of the patients with gouty arthritis, an estimated 300,000 patients in the United States.

In the two phase III trials of approximately 450 patients, most of whom were male and white, (mean age was early 50s) with at least three gouty arthritis attacks a year, a single 150-mg injection of canakinumab, was compared with an intramuscular injection of triamcinolone (40 mg) in treating an acute attack.

Those treated with canakinumab had significantly greater reductions in pain intensity of the affected joint, as measured by changes in a visual pain scale (a primary end point) 72 hours after the injection, compared with those treated with triamcinolone. The risk of having another gouty arthritis flare over the 12 weeks after treatment – the other primary end point – was also significantly reduced among those treated with canakinumab, compared with those on triamcinolone.

The rates of adverse events, including serious adverse events, were higher among those treated with canakinumab, compared with those on triamcinolone and included infections (19% vs. 13%, respectively) and serious infections (2% vs. 0%, respectively). Treatment with canakinumab also was associated with an increase in serum triglycerides levels, declines in renal function, and elevations in serum uric acid, and hypertension. There were three cases of renal failure among gout patients treated with canakinumab, who had predisposing factors, according to the company.

Canakinumab is under review in the European Union for the same indication.

The FDA usually follows the recommendations of its advisory panels. Members of FDA advisory panels have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally they may be given a waiver, but not at this meeting.

ADELPHI, MD. – A Food and Drug Administration advisory panel on June 21 voted 11-1 that the data on canakinumab did not support its approval as a treatment for gouty arthritis attacks, in patients who have not responded adequately to nonsteroidal anti-inflammatory drugs or colchicine.

Members of the FDA’s Arthritis Advisory Committee considered canakinumab a promising treatment, and all but one panelist agreed that the 150-mg subcutaneous dose that was studied in two phase III trials was shown to be effective in treating an attack of gouty arthritis in this population.

But, in another vote, the panel unanimously agreed that the safety profile of canakinumab did not support approval for this indication, because of concerns that included the lack of long-term safety data including the potential long-term risk of infections and the lack of data on the effects of recurrent treatment. (Only 43 patients in the studies had received three or more injections and most had been treated only once.)

The need for more data in likely patient candidates who are less healthy than those in the trials, such as those with advanced renal disease, was another concern cited by the panel. Several panelists also expressed concern that unless use was restricted in some way, canakinumab might be used to treat a broader population than described in the proposed indication.

Canakinumab (Ilaris), a monoclonal antibody that neutralizes interleukin-1beta, was approved in June 2009 for the treatment of a rare disorder, cryopyrin-associated periodic syndromes (CAPS). The new indication proposed by the manufacturer, Novartis Pharmaceuticals, is for the treatment of gouty arthritis attacks in patients who cannot obtain an adequate response with NSAIDs or colchicine.

The company described canakinumab as the first targeted anti-inflammatory treatment for gout, which could be used to treat about 6% of the patients with gouty arthritis, an estimated 300,000 patients in the United States.

In the two phase III trials of approximately 450 patients, most of whom were male and white, (mean age was early 50s) with at least three gouty arthritis attacks a year, a single 150-mg injection of canakinumab, was compared with an intramuscular injection of triamcinolone (40 mg) in treating an acute attack.

Those treated with canakinumab had significantly greater reductions in pain intensity of the affected joint, as measured by changes in a visual pain scale (a primary end point) 72 hours after the injection, compared with those treated with triamcinolone. The risk of having another gouty arthritis flare over the 12 weeks after treatment – the other primary end point – was also significantly reduced among those treated with canakinumab, compared with those on triamcinolone.

The rates of adverse events, including serious adverse events, were higher among those treated with canakinumab, compared with those on triamcinolone and included infections (19% vs. 13%, respectively) and serious infections (2% vs. 0%, respectively). Treatment with canakinumab also was associated with an increase in serum triglycerides levels, declines in renal function, and elevations in serum uric acid, and hypertension. There were three cases of renal failure among gout patients treated with canakinumab, who had predisposing factors, according to the company.

Canakinumab is under review in the European Union for the same indication.

The FDA usually follows the recommendations of its advisory panels. Members of FDA advisory panels have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally they may be given a waiver, but not at this meeting.

ADELPHI, MD. – A Food and Drug Administration advisory panel on June 21 voted 11-1 that the data on canakinumab did not support its approval as a treatment for gouty arthritis attacks, in patients who have not responded adequately to nonsteroidal anti-inflammatory drugs or colchicine.

Members of the FDA’s Arthritis Advisory Committee considered canakinumab a promising treatment, and all but one panelist agreed that the 150-mg subcutaneous dose that was studied in two phase III trials was shown to be effective in treating an attack of gouty arthritis in this population.

But, in another vote, the panel unanimously agreed that the safety profile of canakinumab did not support approval for this indication, because of concerns that included the lack of long-term safety data including the potential long-term risk of infections and the lack of data on the effects of recurrent treatment. (Only 43 patients in the studies had received three or more injections and most had been treated only once.)

The need for more data in likely patient candidates who are less healthy than those in the trials, such as those with advanced renal disease, was another concern cited by the panel. Several panelists also expressed concern that unless use was restricted in some way, canakinumab might be used to treat a broader population than described in the proposed indication.

Canakinumab (Ilaris), a monoclonal antibody that neutralizes interleukin-1beta, was approved in June 2009 for the treatment of a rare disorder, cryopyrin-associated periodic syndromes (CAPS). The new indication proposed by the manufacturer, Novartis Pharmaceuticals, is for the treatment of gouty arthritis attacks in patients who cannot obtain an adequate response with NSAIDs or colchicine.

The company described canakinumab as the first targeted anti-inflammatory treatment for gout, which could be used to treat about 6% of the patients with gouty arthritis, an estimated 300,000 patients in the United States.

In the two phase III trials of approximately 450 patients, most of whom were male and white, (mean age was early 50s) with at least three gouty arthritis attacks a year, a single 150-mg injection of canakinumab, was compared with an intramuscular injection of triamcinolone (40 mg) in treating an acute attack.

Those treated with canakinumab had significantly greater reductions in pain intensity of the affected joint, as measured by changes in a visual pain scale (a primary end point) 72 hours after the injection, compared with those treated with triamcinolone. The risk of having another gouty arthritis flare over the 12 weeks after treatment – the other primary end point – was also significantly reduced among those treated with canakinumab, compared with those on triamcinolone.

The rates of adverse events, including serious adverse events, were higher among those treated with canakinumab, compared with those on triamcinolone and included infections (19% vs. 13%, respectively) and serious infections (2% vs. 0%, respectively). Treatment with canakinumab also was associated with an increase in serum triglycerides levels, declines in renal function, and elevations in serum uric acid, and hypertension. There were three cases of renal failure among gout patients treated with canakinumab, who had predisposing factors, according to the company.

Canakinumab is under review in the European Union for the same indication.

The FDA usually follows the recommendations of its advisory panels. Members of FDA advisory panels have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally they may be given a waiver, but not at this meeting.