Takeda Receives Positive CHMP Opinion for Teduglutide (Revestive®) for Patients with Short Bowel Syndrome (1)

OSAKA, Japan and BEDMINSTER, New Jersey, June 22, 2012 /PRNewswire/ --

        
        - European CHMP adopts positive opinion for teduglutide (Revestive(R)) for
          patients with short bowel syndrome (SBS)
        - SBS is a rare and highly disabling condition that impacts patients' quality of
          life and can lead to serious life-threatening complications
        - 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)

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 authorisation for the medicinal product teduglutide (tradename in Europe: Revestive(R)) as a once-daily treatment for adult patients with short bowel syndrome (SBS). The marketing authorisation application was submitted in March 2011.

SBS is a rare and debilitating disease characterised 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. SBS 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(R)) is a novel, 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."

"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."

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.[1]

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.[1]

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.[2]

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.[2]

About Short Bowel Syndrome

Short bowel syndrome (SBS) is a highly disabling condition that can impair a patient's quality of life and lead to serious life-threatening complications. SBS typically arises after extensive resection of the bowel due to Crohn's disease, ischemia or other conditions. SBS patients often suffer from malnutrition, severe diarrhoea, dehydration, fatigue, osteopenia, and weight loss due to the reduced intestinal capacity to absorb nutrients, water, and electrolytes. The usual treatment for short bowel syndrome is nutritional support, including parenteral nutrition (PN) and/or intravenous (IV) fluids to supplement and stabilize nutritional needs.

Although PN can provide nutritional support for short bowel syndrome patients, it does not improve the body's own ability to absorb nutrients. PN is also associated with serious complications, such as infections, blood clots or liver damage, and the risks increase the longer patients are on PN. Patients on PN often experience a poor quality of life with difficulty sleeping, frequent urination and loss of independence.

About Teduglutide (Revestive(R))

Teduglutide is a novel, recombinant analogue of human glucagon-like peptide 2, a protein involved in the rehabilitation of the intestinal lining. It has been developed to reduce dependence on parenteral nutrition (PN) in adult patients with short bowel syndrome (SBS). Two phase III studies of teduglutide demonstrated a favorable safety profile and significant reductions in mean PN volume from baseline to end of treatment. In addition some patients were able to be weaned off PN and continue their life without parenteral support

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).

In 2007, NPS Pharmaceuticals, Inc. , a specialty pharmaceutical company developing innovative therapeutics for rare gastrointestinal and endocrine disorders, granted Nycomed the rights to develop and commercialize teduglutide outside the United States, Canada and Mexico and Israel. NPS retains all rights to teduglutide in North America. NPS submitted a new drug application for teduglutide to the U.S. Food and Drug Administration (FDA) in November 2011. Teduglutide is known as Gattex(R) in the U.S.

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