Shire gets extension of market authorization in Europe for Revestive to treat paediatric patients with SBS

Patients should be stable following a period of intestinal adaptation after surgery.

"We are very pleased to be able to bring Revestive, the first product indicated specifically to treat paediatric SBS patients in Europe," said Ueli Fankhauser, Head, Global Product Strategy.

"This extension of EU Market Authorization for Revestive represents an important advance in the treatment of SBS in paediatric patients."

SBS is a rare gastrointestinal condition characterised by a clinically significant reduction in intestinal absorptive capacity as a consequence of surgical resection of large portions of the intestine, commonly due to congenital abnormalities, disease or trauma.

The European Commission decision to grant extension of Market Authorization for Revestive in the treatment of paediatric patients with SBS follows a positive opinion adopted by the Committee for Medicinal Products for Human Use (CHMP) in May 2016.

Estimates of the prevalence of SBS with Intestinal Failure (SBS-IF) in children vary markedly, largely due to the lack of standardised reporting and rarity of the disease. In a recent cross-sectional study in the Netherlands (the nationwide DRIFT registry study), the prevalence of chronic IF requiring home parenteral support (PS) was 9.6 per million in children. In the DRIFT registry population, 43.2% of children with chronic IF had SBS, which translates into a Dutch national prevalence of paediatric SBS-IF requiring home parenteral nutrition of 4.1 per million.

Supportive Paediatric Data

A 12-week, open-label, multicentre, safety, pharmacokinetic and pharmacodynamic study was conducted in 42 children aged 1-17 years who had SBS-IF for at least one year and had plateaued in parenteral support (PS) reduction with minimal or no advance in enteral nutrition for at least three months. Of the participants, 37 received teduglutide 0.05 mg/kg/day (n=15); 0.025 mg/kg/day (n=14); 0.0125 mg/kg/day (n=8); and five received standard of care.

Of the 42 patients, 40 (95%) completed the study. Most adverse events were related to gastrointestinal complaints and/or central line-related issues. No deaths were reported, no serious drug-related adverse events were observed, and no patient discontinued the study due to adverse events. No safety signals related to fluid overload, obstruction, hepatobiliary system, or colonic polyps were seen in the study.

Although the study was not powered for efficacy, the data showed that children treated with teduglutide 0.05 mg/kg/day and 0.025 mg/kg/day had reductions from baseline to week 12 in PS volume requirements, and increases from baseline in enteral nutrition volume. Four patients achieved independence from PS (three in the teduglutide 0.05 mg/kg/day group, one in the 0.025 mg/kg/day group). Despite PS reductions, clinical and nutritional status remained stable across the teduglutide treatment groups.

About Short Bowel Syndrome (SBS)

SBS is a rare and potentially life-threatening gastrointestinal condition. It is characterized by a clinically significant reduction in intestinal absorptive capacity as a consequence of surgical resection of large portions of the intestine commonly due to congenital abnormalities, disease or trauma.

If intestinal adaptation is inadequate, the absorptive capacity of the residual intestine becomes insufficient to meet the nutritional, fluid and electrolyte needs to sustain the life and growth requirements of a child; this leads to IF, which requires chronic dependence on PS to maintain adequate growth, hydration, protein, electrolyte, and micronutrient balances. SBS is the most common cause of IF in the paediatric population.