Shares of Kiniksa Pharmaceuticals Ltd. (NASDAQ:KNSA) hit a 52-week high on June 29 as pivotal phase III results showed that Arcalyst (rilonacept), a medicine it licensed from Regeneron Pharmaceuticals Inc., led to a 96% reduction in risk of recurrent pericarditis events among 61 people not helped by standard-of-care (SOC) treatments. Kiniksa now plans to submit an sBLA with the FDA in recurrent pericarditis later this year. Shares in the company closed 12.9% higher on Monday, at $26 each.

A once-weekly IL-1 alpha and IL-1 beta cytokine trap, Arcalyst is already FDA-approved for the treatment of cryopyrin-associated periodic syndromes (CAPS). But it faces tough competition in that indication from Novartis AG's Ilaris (canakinumab), according to DRG, as well as challenges from Swedish Orphan Biovitrum AB's Kineret (anakinra). An sBLA approval secured by Kiniksa could both expand rilonacept's U.S. market and revenues and provide people with recurrent pericarditis the first FDA-approved therapy for the indication.

The Lexington, Mass.-based company, officially domiciled in Hamilton, Bermuda, has been advancing its rilonacept program in pericarditis since at least September 2017. It initially licensed it from Regeneron for $5 million up front plus a pledge of up to $27.5 million in regulatory milestone payments. Should its sBLA win FDA approval, it could potentially see an ongoing return.

A regulatory approval in the indication would automatically expand Kiniksa's license to the drug to include certain rights in CAPS as well as deficiency of the interleukin‑1 receptor antagonist, an indication for which Regeneron filed a separate sBLA in June. Kiniksa would also assume from Regeneron the sales and distribution of rilonacept for approved indications in the U.S. and Japan, evenly splitting profits on sales of the drug in those territories.

Recurrent pericarditis, a painful inflammatory cardiovascular disease, affects a relatively small group of people. Kiniksa estimates there are about 40,000 patients seeking and receiving medical treatment in the U.S., with about 14,000 patients falling into the three main subgroups most likely to benefit from rilonacept: refractory, multiple relapsing and steroid-dependent patients.

But with a breakthrough therapy designation from the FDA in hand and just one other company having disclosed a recurrent pericarditis program, Russia's R-Pharm, rilonacept could be well-positioned to address the market.

On Monday, Kiniksa added strength to its case for the drug's use with new data from its global Rhapsody phase III study. Co-investigators for the trial, from Cleveland Clinic and the University of Torino in Italy, found that, in patients not helped by SOC treatment, rilonacept offered a 96% reduction in risk of recurrent pericarditis events, with a hazard ratio of 0.04 and a “p” value of less than 0.0001.

Patients who were taking nonsteroidal anti-inflammatory drugs, colchicine, or corticosteroids who enrolled in the study were put on rilonacept treatment during a run-in period, then discontinued background medications. Median time to pericarditis recurrence for rilonacept recipients in the randomized withdrawal period of the study could not be estimated due to the low number of recurrences in the rilonacept treatment arm, the company said. The median time-to-recurrence for placebo recipients was 8.6 weeks (hazard ratio = 0.04, p<0.0001).

Kiniksa also reported that, on a major secondary endpoint of the study, 81% of rilonacept recipients maintained clinical response at week 16 of the randomized withdrawal period, compared to 20% of placebo recipients (p=0.0002). Furthermore, the proportion of rilonacept recipients with absent or minimal pericarditis symptoms at week 16 of the randomized withdrawal period was 81% compared to 25% for placebo recipients (p=0.0006).

In addition to rilonacept, Kiniksa's clinical-stage candidates include mavrilimumab, a monoclonal antibody (MAb) targeting GM-CSF receptor; vixarelimab, a MAb targeting oncostatin M receptor beta; and KPL-404, a MAb which inhibits CD40/CD40L interaction.

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