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Rilonacept
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Trade namesArcalyst
Other namesIL-1 Trap
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administration		Subcutaneous
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FormulaC9030H13932N2400O2670S74
Molar mass201209.36 g·mol−1
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Rilonacept, sold under the brand name Arcalyst, is a medication used to treat cryopyrin-associated periodic syndromes, including familial cold autoinflammatory syndrome, and Muckle–Wells syndrome; deficiency of interleukin-1 receptor antagonist; and recurrent pericarditis.[1][2][3] Rilonacept is an interleukin 1 inhibitor.[4]

Rilonacept is a dimeric fusion protein consisting of the ligand-binding domains of the extracellular portions of the human interleukin-1 receptor component (IL-1R1) and IL-1 receptor accessory protein (IL-1RAcP) linked in-line to the fragment-crystallizable portion (Fc region) of human IgG1 that binds and neutralizes IL-1.[5]

Rilonacept was given an orphan drug designation by the U.S. Food and Drug Administration (FDA) and is used for the treatment of cryopyrin-associated periodic syndromes (CAPS), including familial cold autoinflammatory syndrome, Muckle–Wells syndrome.[3][6] Rilonacept is the first drug approved by the FDA to treat recurrent pericarditis.[3] Rilonacept was approved for medical use in the United States in February 2008.[7]

On May 8, 2012, an FDA Advisory Panel voted 11–0 against the approval of rilonacept for the treatment of gout, stating that the benefits did not outweigh the risks associated with the drug.[8]

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Rilonacept

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Rilonacept is a dimeric consisting of the ligand-binding domains of the extracellular portions of human interleukin-1 receptor component 1 (IL-1R1) and IL-1 receptor accessory protein (IL-1RAcP) fused to the Fc portion of human immunoglobulin G1 (IgG1), with a molecular weight of approximately 251 kDa, designed to act as a soluble decoy receptor that binds and neutralizes interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β), and interleukin-1 receptor antagonist (IL-1ra). Marketed under the brand name Arcalyst; developed by , Inc., and commercialized by Kiniksa Pharmaceuticals, it is administered via subcutaneous injection and serves as an interleukin-1 (IL-1) blocker to reduce in specific autoinflammatory conditions by preventing IL-1 from interacting with cell-surface receptors. Developed as a targeted biologic for disorders driven by excessive IL-1 production, rilonacept was first approved by the U.S. (FDA) on February 27, 2008, for the treatment of cryopyrin-associated periodic (CAPS), including familial cold autoinflammatory (FCAS) and Muckle-Wells (MWS), in adults and children 12 years and older. Subsequent approvals expanded its indications: in December 2020, it received approval for the maintenance of remission in deficiency of the interleukin-1 (DIRA) in patients weighing at least 10 kg; and on March 18, 2021, for the treatment of recurrent (RP) and reduction in the risk of recurrence in adults and children 12 years and older, marking the first FDA-approved specifically for recurrent . These approvals were based on clinical trials demonstrating significant reductions in inflammatory markers such as (CRP) and (SAA), as well as improvements in symptom control and . In clinical use, for CAPS, MWS, FCAS, and RP, rilonacept is initiated with a of 320 mg (two 160 mg subcutaneous injections) for adults or weight-based (4.4 mg/kg, maximum 320 mg) for pediatric patients 12 years and older, followed by a weekly maintenance dose of 160 mg (or 2.2 mg/kg, maximum 160 mg). For DIRA in patients weighing at least 10 kg, therapy is initiated directly with a weekly dose of 320 mg for adults or 4.4 mg/kg (maximum 320 mg). Its pharmacokinetics show steady-state trough concentrations of approximately 24 μg/mL in CAPS patients and 23 μg/mL in RP patients after weekly 160 mg dosing, with an elimination of about 7 days. Common adverse reactions include injection-site reactions (such as , swelling, pruritus, and bruising) and upper infections, while serious risks involve increased susceptibility to infections, including opportunistic ones, necessitating careful monitoring and avoidance of live vaccines. No specific contraindications are listed, but therapy should be discontinued in cases of serious or active infections.

Medical uses

Cryopyrin-associated periodic syndromes

Cryopyrin-associated periodic syndromes (CAPS) are a spectrum of rare, inherited autoinflammatory disorders caused by gain-of-function mutations in the gene, which encodes the protein cryopyrin. These mutations result in overactivation of the complex, leading to excessive production of interleukin-1 (IL-1), a potent proinflammatory cytokine that drives recurrent episodes of . Clinical manifestations typically include episodic fever, urticaria-like rash, , and potential organ involvement such as , , and renal . The CAPS spectrum includes familial cold autoinflammatory syndrome (FCAS), the mildest subtype triggered by cold exposure and featuring short-lived symptoms of rash, fever, and arthralgia; and Muckle-Wells syndrome (MWS), an intermediate form with more frequent and prolonged flares of fever, rash, and joint pain, often complicated by progressive and a substantial of systemic that can lead to renal failure. Rilonacept, a soluble receptor that acts as an IL-1 trap, is indicated for the treatment of CAPS, including FCAS and MWS, in adults and children aged 12 years and older. The standard dosing regimen consists of an initial subcutaneous of 320 mg, followed by a weekly of 160 mg thereafter. For pediatric patients weighing less than 72 kg, weight-based dosing is used: a of 4.4 mg/kg (maximum 320 mg) and weekly doses of 2.2 mg/kg (maximum 160 mg). Efficacy in CAPS has been established through phase 3, randomized, -controlled clinical trials involving 47 patients with FCAS or MWS, where rilonacept significantly reduced the frequency of disease flares (P ≤ 0.0001 for multisymptom and single-symptom flares) and overall symptom scores (P ≤ 0.0001) compared to . Treatment also normalized key inflammatory markers, with marked reductions in high-sensitivity (hsCRP; P ≤ 0.0001) and (SAA; P = 0.006) levels, reflecting control of underlying . Long-term open-label extension studies have demonstrated sustained with rilonacept over 72–96 weeks, maintaining reductions in frequency, symptom severity, and inflammatory markers in CAPS patients. By consistently normalizing SAA levels—a strongly associated with deposition—rilonacept helps prevent the progression to , a potentially life-threatening complication in MWS.

Deficiency of interleukin-1 receptor antagonist

Deficiency of interleukin-1 (DIRA) is a rare autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function mutations in the IL1RN gene, resulting in absent or dysfunctional IL-1 (IL-1Ra) and unopposed IL-1 signaling. This leads to severe, early-onset manifesting as pustular rash, multifocal , , joint swelling, , elevated acute-phase reactants, and potentially life-threatening complications such as . Rilonacept is indicated for the maintenance of remission in adult and pediatric patients with DIRA weighing 10 kg or more. Dosing for adults is 320 mg subcutaneously once weekly. For pediatric patients, the dose is 4.4 mg/kg subcutaneously once weekly (maximum 320 mg). Efficacy was demonstrated in a 2-year open-label study (NCT01801449) involving 6 pediatric patients (aged 3.3 to 6.2 years) with DIRA who had previously achieved remission with . After switching to rilonacept, all patients achieved and maintained clinical and inflammatory remission (defined as diary score <0.5, <0.5 mg/dL, absence of rash or bone lesions) at 6 months, with remission sustained through 2 years without the need for corticosteroids.

Recurrent pericarditis

Recurrent pericarditis is characterized by repeated episodes of inflammation of the pericardium, the sac surrounding the heart, often idiopathic or post-viral in origin, which can lead to symptoms such as sharp chest pain that worsens with deep breathing or lying down, pericardial effusion, and in severe cases, the risk of cardiac tamponade. This condition is defined as a relapse occurring after a symptom-free interval of at least four to six weeks following an initial episode of acute pericarditis. Rilonacept's efficacy in recurrent was demonstrated in the phase 3 RHAPSODY trial, a double-blind, -controlled, randomized withdrawal study involving 61 patients aged 12 years and older with active disease despite standard therapies including nonsteroidal anti-inflammatory drugs (NSAIDs), , or corticosteroids. In the trial, all participants received open-label rilonacept during a 12-week run-in phase, during which median time to resolution of was five days and normalization of (CRP) levels occurred in seven days, followed by randomization to continue rilonacept or switch to . The primary endpoint of time to first pericarditis recurrence showed a 96% reduction in risk with rilonacept compared to (hazard ratio 0.04; 95% CI, 0.01-0.18; P < 0.0001), with recurrence rates of 7% (2/30 patients) versus 74% (23/31 patients), respectively, and median time to recurrence on of 8.6 weeks. Based on these results, the U.S. (FDA) approved rilonacept on March 18, 2021, as the first for the treatment of recurrent and reduction in risk of recurrence in adults and pediatric patients aged 12 years and older, including those refractory to conventional treatments. For adults, dosing begins with a of 320 mg administered subcutaneously as two 160 mg injections, followed by a of 160 mg weekly starting on day 7. In pediatric patients aged 12 to 17 years, the is 4.4 mg/kg of body weight (maximum 320 mg), with maintenance at 2.2 mg/kg weekly (maximum 160 mg). Patient eligibility includes individuals aged 12 years and older who have experienced recurrent episodes despite standard care, with no upper age limit specified. Monitoring for treatment response involves serial to assess resolution and measurement of CRP levels to gauge control, alongside regular evaluation of scores.

Adverse effects

Common adverse effects

The most frequently reported adverse effects of rilonacept in clinical trials for cryopyrin-associated periodic syndromes (CAPS) and recurrent are injection site reactions and upper respiratory tract infections. Injection site reactions, including pain, , swelling, pruritus, or bruising, occurred in up to 48% of patients in CAPS trials and 34% of rilonacept-treated patients in the phase 3 recurrent pericarditis trial (versus 6% on ). These reactions are typically mild to moderate, self-resolving within 1 to 2 days, and do not show a dose-dependent increase. To manage them, rotation of injection sites is recommended, and with antihistamines may be considered for pronounced pruritus. Upper respiratory tract infections, such as nasopharyngitis and , were reported in 26% of CAPS patients and 23% of rilonacept-treated patients in the recurrent trial (versus 0% on before bailout). These are generally mild and reflect the drug's mild immunosuppressive effects, with no dose-dependent pattern observed across trials. In the small open-label deficiency of interleukin-1 receptor antagonist (DIRA) trial (n=6 patients), upper respiratory tract infections occurred in 100% of patients, rash in 83%, and sinusitis, otitis media, pharyngitis, and rhinorrhea in 50% each. Gastrointestinal effects, including nausea (approximately 4-10%) and diarrhea (approximately 4-7%), along with abdominal pain, occur less commonly but have been noted in CAPS and pericarditis studies. Other effects such as headache (up to 12%), influenza-like symptoms, and fatigue are also reported at frequencies of 5-12% in these populations, remaining mild and manageable on an outpatient basis. Overall, the incidence of these common effects does not increase with dose in CAPS or recurrent pericarditis trials.

Serious adverse effects

Rilonacept, as an interleukin-1 inhibitor, carries risks of serious due to its immunosuppressive effects. Serious have been reported rarely in CAPS clinical trials and post-approval use, with reported cases including bacterial (one fatal), , and Mycobacterium intracellulare . There is also a potential for tuberculosis reactivation, prompting recommendations for screening patients for prior to initiating therapy, in line with current guidelines for biologic agents. Opportunistic , though rare, have been observed in post-marketing reports, and treatment should be discontinued if a serious develops. Hypersensitivity reactions represent another serious risk, occurring rarely in patients in clinical studies. These may manifest as , with symptoms including , urticaria, swelling of the face or throat, and dyspnea, requiring immediate discontinuation of rilonacept and appropriate medical intervention. Injection-site reactions can occasionally progress to severe outcomes like , though this is uncommon. The immunosuppressive nature of rilonacept raises theoretical concerns for increased risk, particularly with long-term use, though causality remains unclear based on available . Post-marketing has included rare reports of lymphomas and other malignancies, but no definitive link has been established in clinical trials. Hematologic and metabolic effects include transient , reported in isolated cases (e.g., one instance of below 1 x 10^9/L following a high-dose administration), without associated infections in those reports. Lipid profile changes are also notable, with mean increases of 19 mg/dL in total , 10 mg/dL in LDL , and 57 mg/dL in triglycerides observed after 6 weeks of treatment in CAPS patients, affecting a subset though exact incidence rates for clinically significant elevations are not precisely quantified in trials. Across clinical trials, discontinuation rates due to serious adverse effects were low, at less than 5%, reflecting the overall tolerability profile despite these risks. All serious adverse events should be reported to the FDA via MedWatch at 1-800-FDA-1088 or www.fda.gov/medwatch to support ongoing .

Contraindications and precautions

Contraindications

Per the U.S. (FDA), there are no contraindications for rilonacept. However, the (EMA) lists to rilonacept or its excipients and active severe s as contraindications. Treatment should not be initiated in patients with active s, and if a serious develops during , rilonacept must be discontinued. If a reaction occurs during treatment, rilonacept should be immediately discontinued, and appropriate medical initiated.

Precautions in special populations

No formal pharmacokinetic studies of rilonacept have been conducted in patients with renal or hepatic impairment, and no dose adjustments are recommended based on available data. In patients undergoing dialysis, general monitoring for infections is advised due to the immunosuppressive effects of interleukin-1 blockade, though specific data are lacking. In elderly patients, the efficacy, safety, and tolerability of rilonacept are generally similar to those in younger adults, with limited data from 78 patients aged 65 years or older. However, this population may face a higher of serious infections, including a reported case of fatal bacterial in a 71-year-old during studies; initiation should proceed with caution and close monitoring for signs of . Rilonacept may cause fetal harm based on its , though human data are limited and insufficient to inform a drug-associated . Animal reproduction studies revealed no evidence of fetal malformations at doses up to 11 times the maximum recommended human dose, but skeletal variations such as supernumerary occurred at doses of 2 times or greater; the background of major birth defects is 2-4% and of is 15-20%. Effective contraception is recommended during treatment and for at least 6 weeks afterward. For lactating women, it is unknown whether rilonacept is present in human milk, affects breastfed infants, or impacts milk production; the benefits of should be weighed against the mother's need for treatment and any potential adverse effects on the infant from rilonacept or the underlying condition. Rilonacept is approved for use in pediatric patients aged 12 years and older for cryopyrin-associated periodic syndromes (CAPS) and recurrent , and in those weighing at least 10 kg for deficiency of the interleukin-1 (DIRA); safety and effectiveness are not established in younger children or those below 10 kg for DIRA. Growth and development should be monitored in pediatric patients, as interleukin-1 blockade may affect bone ossification or other developmental processes, though specific long-term data are limited. Concurrent administration of live vaccines should be avoided with rilonacept, as the immunosuppressive effects of IL-1 inhibition may diminish vaccine efficacy and increase the risk of infection from the live attenuated organism. Patients should complete all recommended vaccinations, including non-live ones, prior to starting therapy in accordance with current immunization guidelines. Caution is advised in patients with a history of , as treatment with immunosuppressants like rilonacept may increase the risk of developing malignancies, though the specific impact is unknown. In patients with comorbid autoimmune or autoinflammatory conditions beyond approved indications, the immunosuppressive effects warrant careful risk-benefit assessment; additionally, lipid profiles should be monitored 2-3 months after initiation and periodically thereafter, with consideration of lipid-lowering therapy if indicated by cardiovascular risk factors, as increases in total , LDL, HDL, and triglycerides have been observed. Prior to initiating rilonacept, patients should receive all recommended vaccinations according to current guidelines, including inactivated vaccines such as pneumococcal and ; live vaccines should be avoided during treatment due to potential risks of infection and lack of data on response or secondary transmission.

Rilonacept is a dimeric consisting of the ligand-binding domains of the human interleukin-1 receptor type I (IL-1RI) and the IL-1 receptor accessory protein (IL-1RAcP), fused to the Fc portion of human immunoglobulin G1 (IgG1). This structure enables it to function as a soluble receptor, capturing interleukin-1 (IL-1) ligands in the and preventing their binding to cell surface receptors. Rilonacept exhibits high-affinity binding to both IL-1α and IL-1β, with equilibrium dissociation constants (Kd) of approximately 1.4 pM for IL-1α and 0.5 pM for IL-1β, which is significantly higher than the affinities of cell surface receptors. It also binds the IL-1 (IL-1Ra) with somewhat lower affinity (Kd ≈ 6.1 pM), though this interaction does not interfere with the antagonist's function in a clinically significant manner. By sequestering these ligands, rilonacept selectively inhibits IL-1 signaling without affecting the processing of pro-IL-1β to its mature form by the . The blockade of IL-1 binding to its receptor complex prevents the recruitment of intracellular signaling molecules, thereby inhibiting downstream activation of the pathway and (MAPK) pathways, including p38, p42/p44 (ERK), and JNK. This interruption reduces the production of pro-inflammatory cytokines such as IL-6 and alpha (TNF-α), attenuating the overall inflammatory response. In clinical contexts, this mechanism leads to rapid normalization of acute-phase reactants like (CRP) and (SAA) in conditions such as cryopyrin-associated periodic syndromes (CAPS) and recurrent .

Pharmacokinetics

Rilonacept is administered via subcutaneous injection and exhibits approximately 50% . Peak plasma concentrations are achieved 2 to 3 days following administration. As a large (molecular weight approximately 251 ), rilonacept is primarily confined to the compartment. Rilonacept undergoes proteolytic degradation typical of therapeutic proteins, with no involvement of hepatic enzymes. Elimination occurs primarily through by the , with a terminal of approximately 7 days and clearance of 0.53 mL/h/kg. Steady-state concentrations are reached after approximately 6 weeks in CAPS patients or 2 weeks in recurrent (RP) patients with weekly dosing, and are linear over the therapeutic dose range. Steady-state trough concentrations are approximately 24 μg/mL in CAPS patients and 23 μg/mL in RP patients following weekly 160 mg doses. No clinically significant differences in the pharmacokinetics of rilonacept were observed based on age, body weight, or . Data on race are limited, with studies primarily in Caucasian patients. No pharmacokinetic studies have been conducted in patients with renal or hepatic impairment; however, no dose adjustment is needed for renal impairment, and hepatic impairment is not expected to significantly affect .

Chemistry

Molecular structure

Rilonacept is a dimeric composed of two identical polypeptide chains. Each chain consists of the ligand-binding domains from the extracellular portions of human interleukin-1 receptor type 1 (IL-1R1, residues 1–333) and interleukin-1 receptor accessory protein (IL-1RAcP, residues 1–354), fused in tandem to the Fc region of human immunoglobulin G1 (IgG1) through short linker peptides. The Fc domain promotes homodimerization of the fusion proteins via disulfide bonds, which enhances binding avidity to interleukin-1 ligands. This structural design allows rilonacept to function as a soluble decoy receptor. Rilonacept is produced recombinantly in ovary (CHO) cells and undergoes N-linked at multiple sites, contributing to its stability and . The of rilonacept is \ceC9030H13932N2400O2670S74\ce{C9030H13932N2400O2670S74}. It is supplied as a sterile, lyophilized for reconstitution prior to and remains stable when stored at 2–8°C in its original carton.

Physical properties

Rilonacept is supplied as a sterile, white to off-white, preservative-free lyophilized in single-use vials, with each vial containing 220 mg of the . For administration, the is reconstituted by adding 2.3 mL of preservative-free , to yield a deliverable volume of approximately 2.75 mL at a concentration of 80 mg/mL. The resulting solution is viscous, clear, and colorless to pale yellow, and it must be free of visible particulates before use. The reconstituted solution is buffered with 46 mM , 50 mM L-arginine, and includes excipients such as (10 mg/mL), (20 mg/mL), and (30 mg/mL), at a of 6.5. This formulation ensures solubility in sterile and provides an isotonic solution suitable for . The product contains no preservatives, necessitating single-use handling to maintain sterility. Unreconstituted vials should be stored refrigerated at 2°C to 8°C (36°F to 46°F) in their original carton to protect from light, and they remain stable until the expiration date printed on the packaging. After reconstitution, the solution is stable for up to 3 hours when stored at (up to 25°C or 77°F) and protected from light, but it must not be frozen or shaken vigorously to avoid denaturation. Any unused portion should be discarded immediately following administration. For delivery, rilonacept is administered via subcutaneous injection, with a maximum volume of 2 mL per injection site to minimize discomfort. Injection sites should be rotated among the , , or , avoiding areas that are bruised, , tender, or hardened, and aseptic technique is required throughout preparation and administration.

History

Development

Rilonacept, a recombinant designed as an interleukin-1 (IL-1) trap, was developed by in the early 2000s to target autoinflammatory diseases driven by excessive IL-1 signaling, particularly cryopyrin-associated periodic syndromes (CAPS). The molecule combines the ligand-binding domains of the IL-1 receptor and IL-1 receptor accessory protein fused to the Fc portion of human IgG1, enabling high-affinity binding to IL-1α (Kd = 1.4 pM), IL-1β (Kd = 0.5 pM), and IL-1 receptor antagonist (Kd = 6.1 pM), thereby neutralizing these cytokines before they can activate inflammatory pathways. Preclinical evaluation focused on demonstrating rilonacept's ability to inhibit IL-1-mediated . In vitro binding assays confirmed its potent blockade of IL-1 signaling by acting as a soluble receptor. Animal models, including pyrogenicity tests, showed that rilonacept effectively prevented IL-1-induced fever and acute-phase responses, supporting its potential to mitigate IL-1-driven autoinflammation without impairing in murine analogs at doses up to 200 mg/kg weekly (approximately sixfold the exposure). No long-term have been conducted to evaluate the carcinogenic potential of rilonacept. The drug has not been evaluated for effects on or reproduction in non- primates. Mutagenicity has not been formally tested. Early clinical development included phase 1 studies assessing safety and in healthy volunteers, which established that subcutaneous rilonacept was well-tolerated with a long supporting weekly dosing. Phase 1/2 trials from 2004 to 2006 advanced to open-label evaluations in CAPS patients. A pilot study in five adults with familial cold autoinflammatory syndrome (FCAS), a CAPS subtype, administered 300 mg followed by 100-160 mg weekly subcutaneously; symptoms such as rash, fever, and joint pain/swelling resolved within days, with normalization of acute-phase reactants like (CRP) and (SAA) by week 2, and no serious adverse events reported over 3-6 months. These findings supported dose selection for larger trials, showing rapid flare reduction in open-label settings. The pivotal phase 3 trial, known as the RAPID study (NCT00288704), enrolled 47 CAPS patients (aged 12-78 years) in a randomized, double-blind, -controlled design with two parts. In part A (6 weeks), 23 patients received 160 mg weekly rilonacept after a 320 mg , achieving an 84% reduction in mean composite symptom scores (from baseline 4.1 to 0.5) compared to 13% in 24 patients (p<0.0001); 87% of rilonacept-treated patients were flare-free responders versus 24% on . Part B (9-week randomized withdrawal) confirmed sustained efficacy, with minimal symptom worsening (score increase of 0.1) in rilonacept continuers versus 0.9 in switchers (p=0.0003). CRP and SAA levels normalized in nearly all rilonacept patients by week 3. Safety was favorable, with injection-site reactions as the most common . Post-approval research expanded rilonacept's evaluation to other IL-1-mediated conditions. In , Regeneron licensed rights to rilonacept to Kiniksa Pharmaceuticals for evaluation in certain IL-1 mediated diseases, including recurrent . The RHAPSODY phase 3 trial (NCT03737110), completed in 2020, assessed rilonacept in 61 adults with recurrent refractory to standard therapies. After a 6-week open-label lead-in (320 mg loading, then 160 mg weekly), responders entered randomized withdrawal; rilonacept reduced pericarditis recurrence risk by 96% versus ( 0.04, p<0.001), with rapid symptom resolution ( score reduction from 5.7 to 0.3 by day 3) and CRP normalization in 89% by week 1. This supported broader indications for autoinflammatory pericardial disease. Key milestones included U.S. designation for CAPS on December 20, 2004, recognizing its potential for this rare condition (prevalence ~1 in 1 million). Regeneron's initial collaboration with for ended in 2004, redirecting focus to CAPS.

Regulatory approvals

Rilonacept, marketed as Arcalyst, was first approved by the U.S. (FDA) on February 27, 2008, for the treatment of Cryopyrin-Associated Periodic s (CAPS), including Familial Cold Autoinflammatory (FCAS) and Muckle-Wells (MWS), in adults and children aged 12 years and older. This approval included a in the product labeling regarding the increased risk of serious infections, advising against initiation in patients with active infections and recommending discontinuation if serious infections occur. As part of the initial approval, the sponsor committed to post-marketing studies, including establishing a pediatric registry to assess the long-term safety of rilonacept in children with CAPS and other rare diseases, focusing on risks such as infections and potential impacts on growth and development. Subsequent supplemental approvals expanded rilonacept's indications in the United States. On December 21, 2020, the FDA approved rilonacept for the maintenance of remission of Deficiency of Interleukin-1 (DIRA) in adults and pediatric patients weighing at least 10 kg. This was followed by approval on March 18, 2021, for the treatment of recurrent and reduction in the risk of recurrence in adults and children aged 12 years and older, extending its use to this pediatric population for the new indication. In December 2024, rilonacept received approval in for the treatment of recurrent . In the , rilonacept received marketing authorization from the (EMA) on October 23, 2009, for the treatment of CAPS in adults and children aged 12 years and older. However, the marketing authorization was voluntarily withdrawn by the marketing authorization holder on October 24, 2012, for commercial reasons, and rilonacept is no longer authorized in the EU. Outside the and former markets, rilonacept has limited regulatory approvals and availability, often through compassionate use or special access programs for indications in select jurisdictions.

Society and culture

Brand names

Rilonacept is primarily marketed under the brand name Arcalyst by , Inc. in the and . Internationally, Arcalyst is available in limited markets, with no generic versions due to its biologic status, which precludes simple generic replication and requires development. The is supplied as 220 mg of rilonacept in single-dose vials containing lyophilized powder for reconstitution prior to subcutaneous injection. Production is handled by Kiniksa Pharmaceuticals (UK), Ltd., under license from Regeneron, with distribution limited to specialty pharmacies to ensure proper handling and patient support. Patent protections have provided market exclusivity, with composition-of-matter patents expiring around 2022 for core uses like cryopyrin-associated periodic syndromes (CAPS), while method-of-use patents and orphan drug exclusivity extend protection for newer indications, such as recurrent pericarditis, until at least 2028 and potentially 2039. Rilonacept is available by prescription only and is not classified as a under the . As a recombinant biologic, it falls under the regulatory oversight of the FDA's Center for Biologics Evaluation and Research. The drug carries a for serious infections due to its interleukin-1 blockade, requiring on infection risks, though no formal Risk Evaluation and Mitigation Strategy (REMS) program is mandated. Rilonacept has received designations from the FDA for cryopyrin-associated periodic syndromes (CAPS) in 2005, deficiency of interleukin-1 receptor antagonist (DIRA) in 2017, and recurrent in 2020, conferring seven years of market exclusivity upon approval for these indications along with tax credits for . In the , rilonacept is primarily covered under , with coverage varying by plan and requiring for certain indications. For eligible patients with limited or no , the Kiniksa OneConnect program provides free medication for up to 12 months, along with support for injection training and financial assistance. Internationally, rilonacept was granted marketing authorization by the for CAPS in 2009 but was withdrawn from the EU market in 2012 at the sponsor's request; orphan designation for recurrent was granted in 2021, but a marketing authorisation application for the treatment of idiopathic pericarditis was withdrawn in February 2025 for business reasons. It is not approved by Australia's and thus unavailable there, limiting access to specialist-prescribed use in jurisdictions like the where it holds approvals. As of November 2025, no biosimilars to rilonacept have been approved worldwide, owing to ongoing patent protections extending into the late and the technical challenges of developing interchangeable biologics.

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  34. https://investors.kiniksa.com/news-releases/news-release-details/kiniksa-announces-fda-approval-arcalyst-r-rilonacept-recurrent
  35. https://pubmed.ncbi.nlm.nih.gov/18668591/
  36. https://investor.regeneron.com/news-releases/news-release-details/key-studies-published-supporting-fda-approval-regenerons
  37. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/125249s000_MedR.pdf
  38. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=196904
  39. https://pubmed.ncbi.nlm.nih.gov/19649332/
  40. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/125249s000_Approv.pdf
  41. https://www.globalreachhealth.com/arcalyst-receives-new-indication-for-rare-inflammatory-disorder/
  42. https://pmc.ncbi.nlm.nih.gov/articles/PMC12379981/
  43. https://www.ema.europa.eu/en/medicines/human/EPAR/rilonacept-regeneron
  44. https://www.drugs.com/history/arcalyst.html
  45. https://investor.regeneron.com/news-releases/news-release-details/arcalysttm-rilonacept-first-and-only-fda-approved-treatment
  46. https://www.drugs.com/ingredient/rilonacept.html
  47. https://www.drugpatentwatch.com/p/biologics/tradename/arcalyst
  48. https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=human&query=Rilonacept
  49. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=649718
  50. https://www.drugs.com/mtm/rilonacept.html
  51. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=561616
  52. https://investors.kiniksa.com/news-releases/news-release-details/kiniksa-announces-us-orphan-drug-designation-rilonacept
  53. https://www.goodrx.com/arcalyst/medicare-coverage
  54. https://arcalysthcp.com/access-and-support
  55. https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu-3-20-2390
  56. https://www.ema.europa.eu/en/medicines/human/EPAR/rilonacept-fgk-representative-service-gmbh
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