SILVER SPRING, MD. – A Food and Drug Administration advisory panel unanimously supported the approval of teduglutide, a recombinant analogue of human glucagon-like peptide-2 (GLP-2) administered subcutaneously, as a treatment to improve the intestinal absorption of fluid and nutrients in adults with short bowel syndrome, at a meeting on Oct. 16.
The FDA’s Gastrointestinal Drugs Advisory Committee voted 12 to 0 that the benefits of teduglutide outweighed the potential risks in patients with short bowel syndrome (SBS). Clinical studies of adults with SBS, who are highly dependent on parenteral nutrition, showed that teduglutide significantly reduced the volume of parenteral nutrition and IV fluids they needed after 6 months of treatment, compared with placebo. While the panelists felt comfortable with the drug’s safety profile, they recommended that more safety data are needed. They also advised following the long-term safety and potential risks of the treatment after approval, including determining whether the risk of colorectal cancer is increased with treatment.
Produced in the small intestine and the proximal large intestine, GLP-2 is "an intestinotrophic peptide that stimulates mucosal epithelium," increasing absorption of fluids and nutrients, according to the manufacturer, NPS Pharmaceuticals. In studies, patients treated with teduglutide had evidence of increased villus height after 21 days of treatment, according to the company.
In a phase III study of 86 adults with SBS, 63% of those treated with 0.05 mg/kg daily had at least a 20% reduction in the volume of parenteral nutrition and IV fluids (the primary end point) required after 24 weeks of treatment, compared with 30% of those on placebo; this was a statistically significant difference. An extension study indicated that this effect is maintained through 1 year of treatment.
If teduglutide is approved, the company will market it as Gattex. About 10,000-15,000 adults in the United States with SBS are dependent on parenteral nutrition and IV fluids for fluid and nutrient replacement, according to NPS. Teduglutide was recently approved in Europe for the same indication. The FDA is expected to make a decision on approval by Dec. 30; if the drug is approved, the company plans to pursue studies in pediatric patients with SBS.
The two drugs currently approved by the FDA for SBS are somatropin rhGH (Zorbtive), a growth hormone approved in 2003, and L-glutamine powder for oral solution (Nutrestore), an adjunctive treatment approved in 2004.
The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.