Regulatory Decision Summary for Xeomin

Xeomin was authorized on the basis of efficacy and safety data provided in the SNDS. There is an unmet need for the treatment of chronic troublesome sialorrhea in pediatric patients with neurological disorders such as cerebral palsy, traumatic brain injury, and/or intellectual disability where existing treatments are inappropriate, note effective or not well tolerated by these patients. Chronic sialorrhea may significantly affect quality of life and result in issues related to wet clothing, skin breakdown, speech and eating difficulties, choking, dehydration, aspiration, and respiratory system infections.

Authorization was based on a phase 3, international, multicenter, study (Study 3091) that included a double-blind, randomized, placebo-controlled, main period (MP) consisting of a single intraglandular injection cycle of 16 weeks duration followed by an open-label extension period (OLEX) period consisting of 3 additional intraglandular injection cycles separated by 16 weeks for a total study duration of 64 weeks. Study participants included 220 children aged 6-17 years with chronic troublesome sialorrhea who were randomized to active treatment or placebo (148 Xeomin and 72 placebo. An additional 35 participants aged 2-5 years were treated with open-label Xeomin only (no placebo group). At the end of the MP, all subjects received open label Xeomin treatment. All subjects received a body weight (BW) based total dose of Xeomin of approximately 2 units/kilogram (U/kg) for subjects with a BW<30 kg, and a fixed dose of 75 units for a BW >30 kg. Subjects with a BW <12 kg were excluded from the study. The total dose of Xeomin was administered by intraglandular injections to the parotid and submandibular glands on both sides with dose divided in a ratio of 3:2 between the parotid and submandibular glands.

The primary analysis consisted of two co-primary endpoints in subjects aged 6-17 years evaluating the change at 4 weeks between Xeomin and placebo treated subjects. The two co-primary endpoints consisted of assessing a change in the unstimulated Salivary Flow Rate (uSFR), which is a standardized procedure of saliva collection during a specified time, and the Global Impression of Change Scale (GICS) scale completed by the child’s caregiver. The uSFR was not obtained in subjects aged 2-5 years as the uSFR method of direct saliva collection was considered inappropriate for children of this age group. Consequently, efficacy in the 2-5 year age group was extrapolated from the results in the 6-17 year old group. Results of the primary analysis for the 6-17 year age group were statistically significant.

The most common adverse reactions (ADRs) reported in at least 1% of Xeomin treated patients (greater than placebo) aged 6-17 years included bronchitis, pharyngitis, headache and vomiting during the MP phase of Study 3091. The most common ADR reported in patients aged 2-5 years after the first Xeomin injection was nasopharyngitis (6%). In the OLEX phase, the most common ADRs were nasopharyngitis and pharyngitis in patients aged 6-17 years, while in patients aged 2-5 years, respiratory tract infection viral, pharyngitis, respiratory tract infection and rhinitis were the most common ADRs. Less common but clinically important ADRs include dysphagia, dry mouth, altered (thickened) saliva. A dental visit at the beginning of treatment is recommended to determine any appropriate measures for dental caries prophylaxis related to Xeomin induced xerostomia.

The recommended dose of Xeomin is based on body weight and the total dose per injection session ranges between 20 Units and maximum of 75 Units. The timing for repeat treatment should be determined based on the actual clinical need of the individual patient, and no sooner than every 16 weeks. See the Product Monograph for details. 

Based on the available information, the benefit-risk assessment appears to be favourable, as the observed benefits can be achieved with effective management of risks as described in the PM and supported by ongoing post-marketing surveillance and pharmacovigilance monitoring.