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Currently Enrolling Trials

General Information

Arcalyst (rilonacept) is a recombinant fusion protein that blocks interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β) signaling.

Arcalyst is specifically indicated for the following:

for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Auto-inflammatory Syndrome (FCAS), and Muckle-Wells Syndrome (MWS) in adults and pediatric patients 12 years and older;
for the maintenance of remission of Deficiency of Interleukin-1 Receptor Antagonist (DIRA) in adults and pediatric patients weighing at least 10 kg;
for the treatment of recurrent pericarditis (RP) and reduction in risk of recurrence in adults and pediatric patients 12 years and older

Arcalyst is supplied as an injection for subcutaneous use. The recommended dose schedule is as follows:

CAPS and Recurrent Pericarditis:

Adults: Initiate treatment with a loading dose of 320 mg delivered as two, 2-mL, subcutaneous injections of 160 mg each, administered on the same day at two different injection sites. Continue dosing with a once-weekly injection of 160 mg administered as a single, 2-mL, subcutaneous injection.
Pediatric patients 12 years to 17 years: Initiate treatment with a loading dose of 4.4 mg/kg, up to a maximum dose of 320 mg, administered as one or two subcutaneous injections, not to exceed single-injection volume of 2 mL per injection site. If the initial dose is given as two injections, administer on the same day at two different sites. Continue dosing with a once-weekly injection of 2.2 mg/kg, up to a maximum of 160 mg, administered as a single subcutaneous injection, up to 2 mL.
If a once weekly dose is missed, instruct the patient to administer the injection within 7 days from the missed dose and then resume the patient’s original schedule. If the missed dose is not administered within 7 days, instruct the patient to administer the dose, starting a new schedule based on this date.

DIRA:

Adults: The recommended dose of Arcalyst is 320 mg, once weekly, administered as two subcutaneous injections on the same day at two different sites with a maximum single-injection volume of 2 mL. Arcalyst should not be given more often than once weekly.
Pediatric patients weighing 10 kg or more: The recommended dose of Arcalyst is 4.4 mg/kg (up to a maximum of 320 mg), once weekly, administered as one or two subcutaneous injections with a maximum single-injection volume of 2 mL. If the dose is given as two injections, administer both on the same day, each one at a different site. When switching from another IL-1 blocker, discontinue the IL-1 blocker and begin Arcalyst treatment at the time of the next dose.

Clinical Trials

The FDA approval of Arcalyst for the treatment of CAPS was demonstrated in a randomized, double-blind, placebo-controlled study with two parts (A and B) conducted sequentially in the same patients with FCAS and MWS. Part A was a 6-week, randomized, double-blind, parallel-group period comparing Arcalyst at a dose of 160 mg weekly after an initial loading dose of 320 mg to placebo. Part B followed immediately after Part A and consisted of a 9-week, patient-blind period during which all patients received Arcalyst 160 mg weekly, followed by a 9-week, double-blind, randomized withdrawal period in which patients were randomly assigned to either remain on Arcalyst 160 mg weekly or to receive placebo. Patients were then given the option to enroll in a 24-week, open-label treatment extension phase in which all patients were treated with Arcalyst 160 mg weekly. Arcalyst -treated patients had a larger reduction in the mean symptom score in Part A compared to placebo-treated patients. In Part B, mean symptom scores increased more in patients withdrawn to placebo compared to patients who remained on Arcalyst. In Part A, patients treated with Arcalyst experienced more improvement in each of the five components of the composite endpoint (joint pain, rash, feeling of fever/chills, eye redness/pain, and fatigue) than placebo-treated patients. In Part A, a higher proportion of patients in the Arcalyst group experienced improvement from baseline in the composite score by at least 30% (96% vs. 29% of patients), by at least 50% (87% vs. 8%) and by at least 75% (70% vs. 0%) compared to the placebo group.

The FDA approval of Arcalyst for the maintenance of remission of DIRA was demonstrated in a 2-year, open label study of 6 pediatric patients who previously experienced clinical benefit from daily injections of an IL-1 receptor antagonist, anakinra. The study population included patients with a loss-of-function IL1RN mutations. Patients had a median age at baseline of 4.8 years (range 3.3 to 6.2), and stopped anakinra treatment 24 hours before initiation of Arcalyst. Remission was defined using the following criteria: diary score of < 0.5 (reflecting no fever, skin rash and bone pain), acute phase reactants (<0.5 mg/dL CRP), absence of objective skin rash, and no radiological evidence of active bone lesions. Following an Arcalyst loading dose of 4.4 mg/kg subcutaneously, patients received a once-weekly maintenance dose of 2.2 mg/kg (up to a maximum 160 mg), and were assessed for remission and possible dose escalation. During the first 3 months of Arcalyst administration at the 2.2 mg/kg dose, five of 6 patients exhibited recurrence of pustular rash and therefore the dose was escalated to 4.4 mg/kg once-weekly (up to a maximum of 320 mg). One patient remained on the 2.2 mg/kg once-weekly dose. All patients met the primary end point of the study, remission at 6 months and sustained the remission for the remainder of the 2-year study. No patient required steroid use during the study.

The FDA approval of Arcalyst for recurrent pericarditis was based on the phase 3 study RHAPSODY, a double-blind, placebo-controlled, randomized withdrawal, multinational study. The study consisted of a 12-week run-in followed by a double-blind, placebo-controlled, randomized withdrawal period. In the run-in period, adult patients received a loading dose of Arcalyst 320 mg followed by 160 mg weekly. Patients between 12 and 17 years of age received a loading dose of Arcalyst 4.4 mg/kg (up to 320 mg) followed by 2.2 mg/kg (up to 160 mg) weekly. During the run-in period, patients tapered and discontinued standard of care therapies. In the withdrawal period, patients were randomized 1:1 to remain on Arcalyst 160 mg weekly or to receive placebo. The randomized withdrawal period continued until the prespecified number of primary efficacy endpoint events (pericarditis recurrence) had accrued. Patients recorded scores for pericarditis pain in a daily diary using the 0 to 10 NRS scale. Measurements of CRP, electrocardiograms, and echocardiograms were conducted at intervals during study visits and to assess pericarditis recurrence. RHAPSODY met its prespecified primary endpoint of time-to-first adjudicated pericarditis recurrence in the randomized withdrawal period and all major secondary efficacy endpoints with statistical significance. The data showed that Arcalyst treatment in the trial improved clinically meaningful outcomes associated with the significant unmet medical need in recurrent pericarditis. There were rapid and sustained reductions in both reported pain and inflammation as early as after the first dose. Median time to treatment response was 5 days, with a 97% treatment response rate. Patients randomized to Arcalyst experienced a 96% reduction in the risk for a recurrent pericarditis event, with 92% of trial days being pain free or at most experiencing minimal pain, compared to 40% of trial days on placebo.

Side Effects

Adverse effects associated with the use of Arcalyst may include, but are not limited to, the following:

injection-site reactions
upper respiratory tract infections

Mechanism of Action

Arcalyst (rilonacept) is an interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β) cytokine trap. Rilonacept blocks IL-1 signaling by acting as a soluble decoy receptor that binds both IL-1α and IL-1β and prevents its interaction with cell surface receptors. Rilonacept also binds interleukin-1 receptor antagonist (IL-1ra).