The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the extension of the approval of Shire's Revestive (teduglutide) 5 mg powder and solvent for solution for injection in paediatric patients (aged one to 17 years) with short bowel syndrome (SBS). Teduglutide is an analogue of human glucagon like peptide 2 (GLP-2) that enhances key structural and functional adaptations in the intestinal mucosa.
The European Commission (EC) will now consider the CHMP positive opinion in its final decision of whether to extend marketing authorisation for teduglutide in paediatric patients with SBS in the European Union; a final decision from the EC is expected in August 2016.
“We are delighted that the CHMP has rendered a favorable recommendation for teduglutide in paediatric patients based on their evaluation of the data and benefit-to-risk balance,” said Philip J. Vickers, Ph.D., head of research and development, Shire. “We await the final decision of the EMA and the potential to bring a new treatment option for children and adolescents suffering from SBS in Europe.”
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.
Revestive is currently indicated in Europe for the treatment of adult patients with SBS, who should be stable following a period of intestinal adaptation after surgery, in Canada for the treatment of adult patients with SBS who are dependent on parenteral support (PS), and in the United States under the name Gattex (teduglutide [rDNA origin]) for injection for the treatment of adult patients with SBS who are dependent on PS.
A 12-week, open-label, multicentre, safety, pharmacokinetic and pharmacodynamic study was conducted in 42 children aged 1-17 years who had SBS with Intestinal Failure (SBS-IF) for at least one year and had plateaued in 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.
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 Intestinal Failure (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.