The biologic drug canakinumab (Ilaris) is effective in treating acute flares of gouty arthritis but is too risky to warrant approval, members of the FDA's Arthritis Advisory Committee said Tuesday.
In a unanimous vote, the 12-member panel indicated that canakinumab's safety is not good enough, considering that the drug's benefit is mainly in symptomatic relief rather than modification of the underlying disease.
However, members of the panel did largely agree that the efficacy data adequately showed that the symptomatic relief was genuine, by an 11-1 vote.
The panel was more divided on the question of whether the drug reduced frequency of subsequent attacks. Members voted 8-4 that the efficacy data supported such a claim.
On the two key votes -- whether the efficacy and safety together justified approval of the drug as a treatment for acute gouty arthritis attacks and to increase time between future attacks -- the panel decisively turned thumbs down, with votes of 11-1 and 12-0, respectively.
In a briefing document prepared for the committee meeting, FDA staff had raised concerns about increased rates of infections, high triglyceride levels, and elevated uric acid levels in blood seen in the drug's clinical trials for gout and rheumatoid arthritis.
Canakinumab, manufactured by Novartis, is a monoclonal antibody targeting the interleukin-1-beta protein. It is already approved for two rare inflammatory diseases, familial cold autoinflammatory syndrome and cryopyrin-associated period syndromes (also known as Muckle-Wells syndrome).
In several studies reported at recent meetings, the drug was found to reduce pain associated with acute gout attacks and cut the frequency of attacks by about 60% to 70% in patients with a history of six to seven flares a year.
But serious infections were seen in 1.7% of the 691 patients treated with canakinumab in the trials, whereas none occurred in about 400 control patients receiving triamcinolone or colchicine. 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," FDA staff asked in a briefing document for the panel.
Increases in triglycerides were noted in many patients receiving the 150-mg dose of canakinumab. About 40% had levels above the normal range, and 10% had levels 2.5 times the upper limit of normal or more.
Increases in serum uric acid of more than 2 mg/dL affected 36% of patients in one trial and 27% in another, with both proportions higher than in triamcinolone-treated patients.
FDA staff also questioned whether Novartis's proposed dosing recommendation -- a single 150-mg subcutaneous injection followed by additional doses "on demand" -- would more properly be considered chronic treatment, rather than a remedy for acute attacks.