Regulatory Decision Summary for BELKYRA

The data from 18 Phase 1 to Phase 3 studies with 1,575 subjects exposed to deoxycholic acid for up to 4 years of follow-up post-treatment were submitted. Efficacy and safety were supported by two pivotal phase 3, randomized, placebo-controlled, double-blind trials enrolling 515 adult subjects with moderate to severe submental fat (SMF) treated with Belkyra for up to 6 sessions one month apart, each consisting of up to 50 injections of 0.2 mL each, administered into SMF and spaced 1 cm apart for a duration of 44 weeks including 24 weeks of follow-up post-treatment.

The co-primary composite efficacy endpoint, the proportion of subjects with a least 1 and 2 grade improvements on the clinician and patient-reported SMF rating scales 12 weeks after final treatment, demonstrated statistically significant results favouring Belkyra (68.2% and 16% for Belkyra subjects compared to 20.5% and 1.5% of placebo subjects, respectively). The primary efficacy results were supported by the secondary efficacy endpoints, the proportion of subjects who achieved at least 10% reduction in submental volume assessed by Magnetic Resonance Imaging (MRI), and change in patient-reported submental fat impact score (PR-SMFIS) from baseline to 12 weeks post-treatment.

Most adverse events (AEs) observed in the clinical trials were local treatment-area associated reactions, the majority being mild and self-limited.

Risk mitigation was achieved through accurate labeling of safety issues and a Risk Management Plan reviewed by the Marketed Health Products Directorate (MHPD).

Important limitations of use, as stated in the labelling, include prevention of use for body areas other than SMF, use in patients with mild or extreme amounts of SMF, and a requirement for health professional training prior to use.

The Risk Management Plan includes requirements for a registry, a healthcare professional (HCP) training program and a restrictive distribution only to trained HCPs.

Overall, the data support a favourable benefit/risk profile for Belkyra for improvement in the appearance of moderate to severe convexity or fullness associated with SMF in adults.