Regulatory Decision Summary for Kirsty

Kirsty (insulin aspart injection, or continuous subcutaneous infusion with authorized pump) is a biosimilar to the Canadian reference product NovoRapid (insulin aspart).

Comparable pharmacokinetics (PK) and pharmacodynamics (PD) between Kirsty and NovoRapid were established in a comparative PK and PD study conducted in healthy participants. Pre-defined comparability margins of 80.0% to 125.0% for 90% and 95% confidence intervals (CIs) for PK and PD parameters, respectively, were met.

Non-clinical studies comparing Kirsty to reference insulin aspart included in vitro PD studies as well as in vivo toxicity studies. The in vitro studies demonstrated comparable physiochemical properties and biological activity between test articles. The repeat-dose toxicity study did not show toxicity or tolerability concerns for Kirsty that differed from those of the reference insulin aspart.

The efficacy and safety of Kirsty was compared to NovoLog (insulin aspart) in a 24 week, multi-centre, randomized, open-label, parallel group supportive study. The efficacy analysis included 478 patients (238 Kirsty, 240 NovoLog). The primary endpoint, Treatment Emergent Antibody response (TEAR rate), was similar between Kirsty (24.9%) and NovoLog (27.8%) subjects being TEAR positive after 24 weeks of treatment. Secondary endpoints glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), prandial, basal-, and total daily insulin, as well as 7-point self monitored blood glucose (SMBG) were similar between both groups. Numerical differences existed for TEAR positive subjects’ change in HbA1c within the Kirsty group from baseline to 24 weeks, and between the Kirsty and NovoLog group at 24 weeks. These differences were not clinically meaningful. Overall, the efficacy profile of Kirsty is similar to NovoLog following up to 24 weeks of treatment.

The safety profile of Kirsty is similar to that of NovoLog, with comparable numbers of adverse events, treatment related adverse events, and serious adverse events (SAE). There was a slight increase in SAE hypoglycemia for subjects treated with Kirsty compared to NovoLog, but the difference between treatment groups was not clinically meaningful, with similar numbers of treatment discontinuation and subject rescue (with no subject needing rescue medication) in both groups. The development of anti-drug antibodies, neutralizing antibodies, and cross-reactive antibodies were similar in both groups.

The sponsor also sought authorization for an extension of indications; including the use of Kirsty in pediatric populations, and with continuous subcutaneous insulin infusion pump systems. These are both authorized for the Canadian reference biologic. Based on similarity demonstrated through quality, non-clinical, and clinical data, additional studies in support of these extensions to indication were deemed unnecessary, and the aforementioned indications were granted – consistent with the Canadian reference product.

Overall, based on the totality of evidence derived from comparative structural, analytical and functional, nonclinical data, and clinical data, similarity between Kirsty and NovoRapid has been demonstrated. The benefit/risk profile of Kirsty is considered to be similar to the reference product and favourable for the authorized indications.

For more information on Health Canadas decision, please view the Summary Basis of Decision.