Takeda Pharmaceutical Company Limited and NPS Pharmaceuticals, Inc. , jointly announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product teduglutide (Revestive in Europe) as a once-daily treatment for adult patients with short bowel syndrome (SBS).
SBS is a rare but debilitating disease characterized by the body's severely impaired ability to absorb nutrients and fluids through the gastrointestinal tract in people who have had a significant portion of their small intestine removed. Short bowel syndrome typically arises after extensive surgical resection of the bowel due to Crohn's disease, ischemia or other conditions. Many patients with SBS depend on chronic parenteral nutrition (PN) and/or intravenous (IV) fluids to survive. There are currently no therapies approved for the treatment of SBS in Europe.
Teduglutide (Revestive) is a recombinant analogue of human glucagon-like peptide 2 (GLP-2), a naturally occurring protein involved in the rehabilitation of the intestinal lining. Teduglutide has received orphan drug designation for the treatment of SBS from the European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA).
"Short bowel syndrome patients suffer from malnutrition and diarrhoea, and often parenteral nutrition is necessary to maintain life," said Professor Palle Bekker Jeppesen, M.D., Ph.D, Department of Medical Gastroenterology, Rigshospitalet, University Hospital of Copenhagen, Denmark. "Revestive is a new, unique and important treatment option for our patients and is adding important value to the limited treatment armamentarium."
The CHMP opinion was based upon data from STEPS, the pivotal phase-3 double-blind, placebo-controlled study in patients with SBS, who required parenteral nutrition; 43-patients were randomised to a subcutaneous 0.05-mg/kg/day dose of teduglutide and 43-patients to placebo for up to 24-weeks.
The proportion of teduglutide treated subjects achieving a 20% to 100% reduction of parenteral nutrition at Week-20 and 24 was statistically significantly different from placebo, (63% versus 30%, p=0.002). Treatment with teduglutide resulted in a 4.4-l/week reduction in parenteral nutrition requirements versus 2.3-l/week for placebo at 24-weeks (p<0.001). 21 patients treated with teduglutide (54%) versus nine on placebo (23%) achieved at least a one day reduction in parenteral nutrition administration (p=0.005) Teduglutide was well-tolerated in the doses, frequency, and duration of treatment used in this study.
In another phase-3 double-blind, placebo-controlled study in patients with SBS, who required parenteral nutrition, patients subcutaneously received a 0.05-mg/kg/day dose (n-=-35), a 0.10-mg/kg/day dose (n-=-32) of teduglutide or placebo (n-=-16) for up to 24-weeks.
The primary efficacy analysis of the study results showed no statistically significant difference between the group on teduglutide 0.10-mg/kg/day and the placebo group, while the proportion of subjects receiving the recommended teduglutide dose of 0.05-mg/kg/day achieving at least a 20% reduction of parenteral nutrition at Week-20 and-24 was statistically significantly different versus placebo (46% versus 6%, p<0.01). Treatment with teduglutide resulted in a 2.5-l/week reduction in parenteral nutrition requirements versus 0.9-l/week for placebo at 24-weeks (p=0.08). Teduglutide was well tolerated at the 0.05 mg/kg daily dose for the duration of treatment of adult SBS subjects.
"We welcome the positive opinion from the CHMP for teduglutide. This is good news for patients with SBS," said Trevor Smith, Head of Commercial Operations, Europe&Canada, of Takeda.
"We are pleased with the Committee's recommendation, which brings us closer to our goal of making teduglutide available in Europe for patients with short bowel syndrome," said Francois Nader, MD, President and Chief Executive Officer of NPS Pharmaceuticals. "Teduglutide represents an important treatment advance that could significantly reduce or even eliminate parenteral nutrition support for patients with short bowel syndrome. We congratulate our partner Takeda on receiving this positive opinion and look forward to supporting their efforts to bring this much-needed therapy to patients."
 Publication of STEPS is in preparation. First results were report at the AGA 2011 in an abstract: Jeppesen PB, Pertkiewicz M, Seidner DL, O'Keefe S, Heinze H, Joelsson B: Teduglutide, a novel analogue of Glucagon-like Peptide 2 (GLP-2), is effective and safe in reducing parenteral support volume in short bowel syndrome-intestinal failure subjects: Results from a 24-week, placebo-controlled phase 3 trial (STEPS), Gastroenterology 2011; 140 (5), Supplement 1, S146
 Jeppesen PB, Gilroy R, Pertkiewicz M, Allard JP, Messing B, O'Keefe SJ. Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome. Gut. 2011 Jul;60(7):902-14. Epub 2011 Feb 11.