What Changed FDA’s Mind About Ilaris for Gout?

The FDA quietly approved the interleukin (IL)-1 inhibitor canakinumab (Ilaris) for gout 10 days ago, with no announcement from either the agency or the drug’s manufacturer, Novartis — leaving outsiders to guess at what changed in the dozen years since the company’s first attempt to gain approval fell short.

Canakinumab has been approved in the U.S. for a variety of rare conditions, including periodic fever syndromes and systemic juvenile idiopathic arthritis, but Novartis has kept its sights on broader markets. But when the FDA initially considered the firm’s application for a gouty arthritis indication in 2011, an advisory committee voted to recommend against approval, citing inadequate safety data and evidence the drug provided only symptomatic relief rather than actual disease modification; the agency then rejected the application. (The European Medicines Agency was less picky about the data, approving the gouty arthritis indication in 2013.)

Since that time, few studies have appeared publicly that directly supported canakinumab for gout. The most prominent was a substudy from a trial called CANTOS, reported in 2017, which focused primarily on cardiovascular disease prevention. (Novartis also sought, but failed to obtain, approval in that indication too.) Many CANTOS participants also had gout, and the investigators sought to determine whether the drug helped prevent gout flares.

It did, but not by very much — an absolute risk reduction of just a few percentage points, leading one observer to estimate a number needed to treat of 5,200.

It’s unclear what new data Novartis provided to change the FDA’s mind after the 2011 rejection. Of the 12 trials listed on ClinicalTrials.gov involving gout, most were conducted prior to that time; two commenced in and around 2011, one with the aim of winning approval in China. The other, completed in 2013, was an 18-month extension of previous extension studies, showing modest efficacy but double the rate of overall and serious adverse events relative to triamcinolone.

Nevertheless, on August 25, the FDA notified Novartis that its supplemental biologics license application had been approved. Another 5 days elapsed before anyone in the media noticed that an approval letter was posted. As of September 5, Novartis still hadn’t updated the drug’s official label nor canakinumab’s dedicated website to reflect the new indication.

According to the approval letter, canakinumab can be prescribed for “gout flares in adults in whom non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine are contraindicated, are not tolerated, or do not provide an adequate response, and in whom repeated courses of corticosteroids are not appropriate.”

The approval also raises questions of affordability, given that canakinumab is an expensive branded biologic drug. A single dose lists for nearly $18,000; whether insurers will cover it is uncertain, given that gout flares aren’t life-threatening in and of themselves. It also must compete with anakinra (Kineret), another anti-IL-1 treatment, which reportedly costs less than $1,400 per dose. It’s not approved for gout flare therapy but is widely recommended as an off-label alternative to colchicine, NSAIDs, and steroids. Of course, Novartis has patient assistance programs that may defray some or all of canakinumab’s out-of-pocket expense.