Four years after the EMA first approved Novartis AG's Ilaris (canakinumab) for the treatment of adult-onset Still’s disease (AOSD), the FDA has followed suit, giving it a green light in the indication following a priority review. The rare rheumatic condition usually affects younger adults and can occur as infrequently as once, but also intermittently or chronically.

Robust epidemiologic data on adult-onset Still's disease (AOSD) don't exist, possibly due in part to its status as what Orphanet calls "a diagnosis of exclusion," meaning that it's only identified once other possible diagnoses have been ruled out. Nonetheless, its prevalence is estimated to be more than one out of 100,000 people. Three medicines are approved for the indication globally, including Ilaris, Swedish Orphan Biovitrum AB's Kineret (anakinra) in Europe and Roche Holding AG's Actemra (tocilizumab) in Japan.

AOSD can include symptoms such as painful arthritis, fevers and rash. Most people with the condition also have elevated C-reactive protein levels and an elevated erythrocyte sedimentation rate. As it progresses, the disease can lead to chronic arthritis and other complications. "In general, treatments aim to control inflammation, and prevent joint damage and other complications," according to the NIH Genetic and Rare Diseases Information Center. "Depending on severity and whether long-term management is needed, medications used may include nonsteroidal inflammatory drugs, glucocorticoids, nonbiologic or biologic disease-modifying antirheumatic drugs."

Though the cause of AOSD is unknown, the role of interleukin-1 (IL-1), a type of cytokine important in regulating the body’s immune system is well-established in both AOSD and systemic juvenile idiopathic arthritis (SJIA), the FDA said. Ilaris, like Kineret, works by blocking the effects of IL-1 and suppressing inflammation in patients with the diseases. Actemra, by contrast, works as an IL-6 receptor antagonist. All three medicines are approved to treat SJIA, which has significant overlap in symptoms AOSD, suggesting the indications are part of "a disease continuum rather than two separate disease," the FDA said. Both SJIA and AOSD, are referred to as Still’s disease. Ilaris landed its FDA approval for SJIA in May 2013.

The FDA said that Novartis established the medicine's safety and efficacy for AOSD patients using comparable pharmacokinetic exposure and extrapolation of established efficacy of the drug in patients with SJIA, as well as data on its safety in patients with AOSD and other diseases.

Furthermore, scientists from Italy, the Netherlands, and the U.S. have investigated Ilaris' efficacy as first-line biologic in AOSD. In 2019, they reported that all patients in a small study treated with Ilaris showed "striking clinical responses, within days of initiation. Fever and skin rash disappeared first, followed by progressive improvement in arthritis." Furthermore, "if present, inflammatory organ involvement also responded to treatment," they wrote in Arthritis Research & Therapy. Later data, presented at the 83rd American College of Rheumatology annual meeting, indicated that half of the 10 patients enrolled in the study saw complete responses to the drug.

First launched in 2009, Ilaris generated global revenue of $671 million for Novartis in 2019, primarily from musculoskeletal and pain indications, according to DRG. Sales in that therapeutic category, in which Ilaris is also approved for the treatment of cryopyrin-associated periodic syndromes, have grown year over year. Approvals for SJIA in the U.S. and EU, an additional indication for gouty arthritis in the EU, and other label expansions have helped grow the drug's market.

Though the U.S. AOSD market is likely to be small, at least for now, it doesn't appear that Novartis will face any immediate officially sanctioned competition from Kineret and Actemra. According to Clinicaltrials.gov, Sobi appears to have terminated its Anastills study (NCT03265132) in SJIA and AOSD because meeting the 81-patient enrollment target "will not be feasible within reasonable time," suggesting that it may succumb to the common trial recruitment difficulties drug developers have faced across the globe due to COVID-19. It’s unclear whether Roche has plans to seek U.S. approval for Actemra is AOSD.

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