Regulatory Decision Summary for Kineret

Assessment of the efficacy and safety of Kineret (anakinra) for the treatment of CAPS (including NOMID, MWS and FCAS) was primarily based on a single long-term, prospective, phase 1/2, open-label uncontrolled study of 43 adult and pediatric patients with NOMID. Additionally, a literature search identified 5 published prospective studies, 4 retrospective chart reviews and 98 case reports in patients with NOMID, MWS and FCAS. The benefit/risk ratio of Kineret was considered as follows:

Benefit: In the phase 1/2 study, NOMID symptoms were assessed with a disease-specific diary symptom sum score (DSSS) that included the prominent disease symptoms fever, rash, joint pain, vomiting and headache. The range of possible scores was zero to 20. A total of 43 NOMID patients, ranging in age from 8 months to 46 years, were treated with Kineret at an initial dose of 1 to 2 milligrams per kilogram per day (mg/kg/day) administered subcutaneously, with individualized dose adjustments of 0.5 to 1 mg/kg allowed in patients who were not in clinical remission. The average maintenance dose was 3 to 4 mg/kg daily. The maximum dose administered was 8.2 mg/kg/day. In the ITT analysis set (n=29), mean baseline DSSS was 4.5 (minimum 0.5, maximum 14.5). The primary endpoint (the estimated change in DSSS from baseline to Month 3-6, based on a repeated measures analysis of covariance model) was: -3.5 (95% CI -3.7 to -3.2). Improvement was observed in serum markers of inflammation. For 11 patients who went through a withdrawal phase, disease symptoms and serum markers of inflammation worsened after withdrawal and responded to reinstitution of Kineret treatment. In the absence of a control group, the efficacy of Kineret in preventing disease-associated organ damage could not be confirmed.

Results of the published studies and case reports in NOMID, MWS and FCAS could not be validated.

Risk: The safety profile of Kineret in NOMID was consistent overall with the known safety profile in other patient populations. No new safety signals were identified, but long term safety data were limited especially for children < 2 years of age.

The benefit/risk assessment was considered favourable for the treatment of NOMID patients aged 8 months and older with a body weight of 10 kg or above. Although a targeted treatment is currently authorized in Canada for the treatment of all three forms of CAPS, children < 2 years of age are not included. Given the onset of NOMID in early infancy and the severity of this rare, debilitating disease, the need for effective treatment is therefore especially great in this group. Adequate evidence for the benefit of Kineret treatment was provided for the NOMID population, with an acceptable safety profile. It is further noted that easy titratability due to the daily administration of Kineret may be advantageous for some patients.

A favourable benefit/risk assessment was not established for MWS and FCAS, which are less severe forms of CAPS. In the absence of verifiable study results, it was not possible to confirm a benefit of Kineret treatment in these populations to balance the known risks of treatment, which include the high proportion of serious infections observed in NOMID patients and in other populations, including opportunistic serious infections.

To ensure that the benefit continues to outweigh any risk after authorization, Health Canada has required several post-approval activities to monitor long-term safety.