Ilaris (canakinumab) - 6 indications

Scroll down for information on each indication:

• Cryopyrin-Associated Periodic Syndrome (CAPS); approved June of 2009
• Systemic Juvenile Idiopathic Arthritis; approved May 2013
• Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS), Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD) and Familial Mediterranean Fever (FMF); approved September 2016
• active Still’s disease, including Adult-Onset Still’s Disease; approved June of 2020

General Information

Ilaris (canakinumab) is a human monoclonal anti-human IL-1ß antibody. Canakinumab binds to human IL­1ß and neutralizes its activity by blocking its interaction with IL-1 receptors, but it does not bind IL-1a or IL-1 receptor antagonist (IL-1ra).

Ilaris is specifically indicated for the following:

• the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), in adults and children 4 years of age and older, including Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS)
• for the treatment of Systemic Juvenile Idiopathic Arthritis (SJIA) in patients aged 2 years and older
• the treatment of Tumor Necrosis Factor (TNF) Receptor Associated Periodic Syndrome (TRAPS) in adult and pediatric patients
• for the treatment of Hyperimmunoglobulin D (Hyper-IgD) Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD) in adult and pediatric patients
• for the treatment of Familial Mediterranean Fever (FMF) in adult and pediatric patients
• for the treatment of active Still’s disease, including Adult-Onset Still’s Disease (AOSD)

Ilaris is supplied as a lyophilized powder for solution for subcutaneous injection. Scroll down to see the recommended dosing/administration for each indication.

Mechanism of Action

Ilaris (canakinumab) is a human monoclonal anti-human IL-1ß antibody. Canakinumab binds to human IL­1ß and neutralizes its activity by blocking its interaction with IL-1 receptors, but it does not bind IL-1a or IL-1 receptor antagonist (IL-1ra).

Side Effects

Adverse effects associated with the use of Ilaris for the treatment of CAPS may include, but are not limited to, the following:

• nasopharyngitis
• diarrhea
• influenza
• rhinitis
• nausea
• headache
• bronchitis
• gastroenteritis
• pharyngitis
• weight increased
• musculoskeletal pain
• vertigo

Adverse effects associated with the use of Ilaris for the treatment of TRAPS, HIDS/MKD, and FMF may include, but are not limited to, the following:

• injection-site reactions
• nasopharyngitis

Adverse effects associated with the use of Ilaris for the treatment of Stills disease may include, but are not limited to, the following:

• infections (nasopharyngitis and upper respiratory tract infections)
• abdominal pain
• injection-site reactions

Indication 1 - Cryopyrin-Associated Periodic Syndrome (CAPS)

approved June of 2009

Dosing/Administration

The recommended dose of Ilaris is 150 mg for CAPS patients with body weight greater than 40 kg. For CAPS patients with body weight greater than or equal to 15 kg and less than or equal to 40 kg, the recommended dose is 2 mg/kg. For children 15 to 40 kg with an inadequate response, the dose can be increased to 3 mg/kg. Ilaris is administered every 8 weeks.

Clinical Trial Results

The FDA approval of Ilaris was based on a three part study in patients 9 to 74 years of age with the MWS phenotype of CAPS. The subjects weighing more than 40 kg received Ilaris 150 mg and those weighing 15 to 40 kg received 2mg/kg. Part 1 was an 8-week open-label, single-dose period where all subjects received Ilaris. Subjects who achieved a complete clinical response and did not relapse by Week 8 were randomized into Part 2, a 24-week randomized, double-blind, placebo-controlled withdrawal period. Subjects who completed Part 2 or experienced a disease flare entered Part 3, a 16-week open-label active treatment phase. The primary endpoint was complete response, defined as ratings of minimal or better for physician’s assessment of disease activity (PHY) and assessment of skin disease (SKD) and serum levels of C-Reactive Protein (CRP) and Serum Amyloid A (SAA) less than 10 mg/L. In Part 1, a complete clinical response was observed in 71% of subjects one week following initiation of treatment and in 97% of subjects by Week 8. In the randomized withdrawal period, a total of 81% of the subjects randomized to placebo flared as compared to none (0%) of the patients randomized to Ilaris. At the end of Part 2, all 15 subjects treated with Ilaris had absent or minimal disease activity and skin disease. Markers of inflammation CRP and SAA normalized within 8 days of treatment in the majority of subjects. Normal mean CRP and SAA values were sustained throughout the study in subjects continuously treated with canakinumab. After withdrawal of canakinumab in Part 2 CRP and SAA values again returned to abnormal values and subsequently normalized after reintroduction of canakinumab in Part 3.

Indication 2 - Systemic Juvenile Idiopathic Arthritis

approved May 2013

Dosing/Administration

The recommended dose of Ilaris for patients with a body weight greater than or equal to 7.5 kg is 4 mg/kg (with a maximum of 300 mg) administered every 4 weeks.

Clinical Trial Results

The FDA approval of Ilaris for SJIA was based on two studies, (SJIA Study 1 and SJIA Study 2). Subjects enrolled were aged 2 to less than 20 years with a confirmed diagnosis of SJIA at least 2 months before enrollment. The subjects were allowed to continue their stable dose of methotrexate, corticosteroids, and/or NSAIDs without change, except for tapering of the corticosteroid dose as per study design in SJIA Study 2.
SJIA Study 1
This randomized, double-blind, placebo-controlled, single-dose 4-week study assessed the short term efficacy of Ilaris in 84 subjects who were randomized to receive a single subcutaneous dose of 4 mg/kg Ilaris or placebo. The primary endpoint was the superiority of Ilaris versus placebo in the proportion of patients who achieved at least 30% improvement in an adapted pediatric American College of Rheumatology (ACR) response criterion which included both the pediatric ACR core set (ACR30 response) and absence of fever (temperature less than or equal to 38°C in the preceding 7 days) at Day 15. At Day 15 the ACR30 was 84% versus 10% in the Ilaris versus placebo arms, respectively. At Day 29 the ACR30 rates were 81% versus 10%, respectively. Among the patients who returned for a Day 15 visit, the mean change in patient pain score (0-100 mm visual analogue scale) was -50.0 mm on Ilaris, as compared to +4.5 mm on placebo. The mean change in pain score among Ilaris treated patients was consistent through Day 29. All patients treated with laris had no fever at Day 3 compared to 87% of patients treated with placebo.
SJIA Study 2
This randomized, double-blind, placebo controlled, withdrawal study evluated flare prevention by Ilaris. Flare was defined by worsening of greater than or equal to 30% in at least 3 of the 6 core Pediatric ACR response variables combined with improvement of greater than or equal to 30% in no more than 1 of the 6 variables, or reappearance of fever not due to infection for at least 2 consecutive days. The study consisted of two major parts. 177 patients were enrolled in the study and received 4mg/kg Ilaris subcutaneously every 4 weeks in Part I and 100 of these patients continued into Part II to receive either Ilaris 4mg/kg or placebo subcutaneously every 4 weeks. Of the total 128 patients who entered the open-label portion taking corticosteroids, 92 attempted corticosteroid tapering. Fifty-seven (62%) of the 92 patients who attempted to taper were able to successfully taper their corticosteroid dose and 42 (46%) discontinued corticosteroids. Part II was a randomized withdrawal design to demonstrate that the time to flare was longer with Ilaris than with placebo. Follow-up stopped when 37 events had been observed resulting in patients being followed for different lengths of time. The probability of experiencing a flare over time in Part II was statistically lower for the Ilaris treatment group than for the placebo group. This corresponded to a 64% relative reduction in the risk of flare for patients in the Ilaris group as compared to those in the placebo group.

Indications 3, 4 and 5 - Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS), Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD) and Familial Mediterranean Fever (FMF)

approved September 2016

Dosing/Administration

The recommended dose of Ilaris for TRAPS, HIDS/MKD, and FMF patients is based on body weight. For patients with body weight less than or equal to 40 kg, the recommended dose is 2 mg/kg administered every 4 weeks. The dose can be increased to 4 mg/kg every 4 weeks if the clinical response is not adequate. For patients with body weight greater than 40 kg, the recommended dose is 150 mg administered every 4 weeks. The dose can be increased to 300 mg every 4 weeks if the clinical response is not adequate.

Clinical Trial Results

The efficacy and safety of Ilaris for the treatment of TRAPS, HIDS/MKD, and FMF was demonstrated in a 4-Part study (TRAPS, HIDS/MKD, and FMF Study 1) consisting of three separate, disease cohorts (TRAPS, HIDS/MKD, and FMF) which enrolled 185 patients aged greater than 28 days. Patients in each cohort entered a 12-week screening period (Part 1) during which they were evaluated for the onset of disease flare. Patients aged 2 to 76 years were then randomized at flare onset into a 16-week double-blind, placebo-controlled treatment period (Part 2) where they received either 150 mg Ilaris (2 mg/kg for patients weighing less than or equal to 40 kg) subcutaneously or placebo every 4 weeks. Part 3 and Part 4 of this study are ongoing. Randomized patients in Part 2 treated with Ilaris whose disease flare did not resolve, or who had persistent disease activity from Day 8 up to Day 14 (Physician’s Global Assessment [PGA] greater than or equal to 2 or C-reactive Protein [CRP] greater than 10 mg/L and no reduction by at least 40% from baseline) received an additional dose of 150 mg (or 2 mg/kg for patients weighing less than or equal to 40 kg). Patients treated with Ilaris whose disease flare did not resolve, or who had persistent disease activity from Day 15 up to Day 28 (PGA greater than or equal to 2 or CRP greater than 10 mg/L and no reduction by at least 70% from baseline), also received an additional dose of 150 mg (or 2 mg/kg for patients weighing less than or equal to 40 kg). On or after Day 29, patients treated with Ilaris in Part 2 with PGA greater than or equal to 2 and CRP greater than or equal to 30 mg/L were also up-titrated. All up-titrated patients remained at the increased dose of 300 mg (or 4 mg/kg for patients weighing less than or equal to 40 kg) every 4 weeks. The primary efficacy endpoint of the randomized, 16-week treatment period (Part 2) was the proportion of complete responders within each cohort as defined by patients who had resolution of their index disease flare at Day 15 and did not experience a new disease flare during the remainder of the 16-week treatment period. For the primary efficacy endpoint, Ilaris was superior to placebo in the proportion of TRAPS, HIDS/MKD, and FMF patients who resolved their index disease flare at Day 15 and had no new flare over the 16 weeks of treatment from the time of the resolution of the index flare.

Indication 6 - active Still’s disease, including Adult-Onset Still’s Disease

approved June of 2020

Dosing/Administration

The recommended dose of Ilaris for patients with a body weight greater than or equal to 7.5 kg is 4 mg/kg (with a maximum of 300 mg) administered every 4 weeks.

Clinical Trial Results

The efficacy of Ilaris in adults with AOSD is based on the pharmacokinetic exposure and extrapolation of the established efficacy of Ilaris in SJIA patients.  Efficacy of Ilaris was also assessed in a randomized, double-blind, placebo-controlled study that enrolled 36 patients (22 to 70 years old) diagnosed with AOSD. The efficacy and safety data in AOSD were generally consistent with the results of a pooled analysis of SJIA patients.