June 27, 2012 — A novel peptide analogue, teduglutide (Revestive, Nycomed/Takeda), is the first medical treatment recommended for approval by the European Medicines Agency (EMA) for use in adults with short bowel syndrome.
Teduglutide, a recombinant analogue of human glucagon-like peptide 2, was designated as an orphan medicine in the European Union in 2001. Teduglutide is called Gattex in the United States, and the manufacturer (NPS Pharmaceuticals Inc) submitted a new drug application to the US Food and Drug Administration in November 2011.
Clinical trials demonstrated a reduction in parenteral nutrition requirements with the use of teduglutide in patients with short bowel syndrome.
A review by the EMA's Committee for Medicinal Products for Human Use showed that about two thirds of adverse events associated with teduglutide were mild or moderate in severity and mainly related to the gastrointestinal system; about one third were considered to be severe, however, and were predominately related to hepatobiliary and pancreatic events.
"The Committee considered that the safety profile was manageable and, given the benefits of [teduglutide] in the treatment of a patient population in need of alternative therapeutic options, the Committee recommended granting a marketing authorisation," stated an EMA press release.
The marketing authorization application was submitted in March 2011. The agency's recommendation will be decided on by the European Commission.
The recommendation was based on data from the Study of Teduglutide Effectiveness in Parenteral Nutrition (PN)-Dependent Short Bowel Syndrome Subjects (STEPS) pivotal phase 3 trial. The trial included 86 patients, 43 of whom were randomly assigned to receive a subcutaneous 0.05 mg/kg/day dose of teduglutide, and 43 of whom were randomly assigned to receive placebo for up to 24 weeks.
The proportion of teduglutide-treated patients achieving a 20% to 100% reduction of parenteral nutrition at week 20 and 24 was significantly lower compared with placebo (63% vs 30%; P = .002).
Treatment with teduglutide resulted in a 4.4 L/week reduction in parenteral nutrition requirements vs a 2.3 L/week reduction for placebo at 24 weeks (P < .001). In addition, 21 patients (54%) treated with teduglutide achieved at least a 1-day reduction in parenteral nutrition administration vs 9 patients (23%) receiving placebo (P = .005).
Another phase 3 trial included patients who received a 0.05 mg/kg/day dose of teduglutide (n = 35), a 0.10 mg/kg/day dose (n = 32), or placebo (n = 16) for up to 24 weeks.
The primary efficacy analysis showed no significant difference between the group receiving teduglutide 0.10 mg/kg/day and the placebo group. In contrast, the proportion of patients receiving the recommended teduglutide dose of 0.05 mg/kg/day and achieving at least a 20% reduction of parenteral nutrition at weeks 20 and 24 was significantly better than with placebo (46% vs 6%; P < .005).
Treatment with teduglutide resulted in a 2.5 L/week reduction in parenteral nutrition requirements vs 0.9 L/week for placebo at 24 weeks (P = .08).
At this time, no medical treatments are available for short bowel syndrome.
"Teduglutide represents an important treatment advance that could significantly reduce or even eliminate parenteral nutrition support for patients with short bowel syndrome," said Francois Nader, MD, president and chief executive officer of NPS Pharmaceuticals, in a company press release in support of this recent recommendation.
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Cite this: Teduglutide for Short Bowel Given Positive Response in EU - Medscape - Jun 27, 2012.