CHICAGO – Phase III data from a randomized, placebo-controlled trial indicate that the novel agent teduglutide reduces the need for parenteral support in patients with short-bowel syndrome.
At week 20 and week 24, 63% of patients who were randomized to teduglutide (Gattex) achieved at least a 20% reduction in the volume of parenteral fluid required, compared with baseline. Only 30% of patients receiving the placebo achieved this degree of reduction in their parenteral nutrition needs (P = .002), said lead author Dr. Palle B. Jeppesen during a late-breaking abstract session at the annual Digestive Disease Week.
Short-bowel syndrome (SBS) results from removal of the small intestine because of Crohn’s disease, cancer, or other conditions, and is characterized by malabsorption of nutrients, fluids, and electrolytes, as well as diarrhea. An estimated 10,000-15,000 SBS patients in North America are dependent on parenteral nutrition (PN) for their fluid and nutritional needs, at an annual cost that can exceed $100,000 per patient.
"This has a tremendous impact on their life situation, and of course, what we would like to do is provide them with some treatment, getting them off their parental support," said Dr. Jeppesen, with the Copenhagen University Hospital.
Teduglutide is a recombinant analogue of glucagonlike peptide 2, a peptide that enhances intestinal absorption by thickening the intestinal mucosa and increasing villus height and crypt depth.
Teduglutide has been designated an orphan drug for the treatment of SBS by the Food and Drug Administration and the European Medicines Agency. An application was submitted in March to market teduglutide with the brand name Revestive in Europe as a once-daily subcutaneous treatment for SBS, with a similar application under the brand name Gattex expected later this year in the United States, according to study sponsor NPS Pharmaceuticals. In the STEPS (Study of Teduglutide in PN-Dependent Short-Bowel Syndrome) trial, patients had at least 12 continuous months of PN support prior to enrollment; required PN at least three times weekly to meet caloric, fluid, or electrolyte needs; and had a body mass index of at least 15 kg/m2.
After an initial 30-day stabilization period, 86 patients were randomized to subcutaneous teduglutide 0.05 mg/kg or placebo once daily for 24 weeks. One patient in the teduglutide group was randomized in error and not treated.
At baseline, the teduglutide and placebo groups were similar in age (51 years vs. 50 years), weight (63 kg vs. 62 kg), estimated mean small bowel length (84 cm vs. 69 cm), and mean baseline liters of intravenous PN fluid per week (12.5 L vs. 13.4 L).
At week 24, the mean absolute reduction in PN fluid required by the patient was 4.4 L in the teduglutide group vs.2.3 L in the placebo group (P less than .001), Dr. Jeppesen said.
Significantly more patients who were treated with teduglutide had one or more additional days off parenteral infusions (54% vs. 23%; P = .0047). "Having days off parenteral support is an important issue for their social life," he said.
During a discussion of the study, an attendee asked whether patients will be able to take teduglutide cyclically or will need the drug continually for the rest of their lives. Dr. Jeppesen replied that "it is going to be like treating diabetes. It only works when you give them insulin, and it’s the same case with this drug. It works as long as you give it, and when you take it off they go back to their baseline."
Audience members then asked whether there are any long-term effects of teduglutide, particularly in light of concerns that were raised early on about tumor promotion, which have been reportedly addressed by NPS Pharmaceuticals. Dr. Jeppesen said there is no reason to expect any problems and that the drug has a very good safety profile.
Another attendee asked whether teduglutide is likely to be helpful for unstable patients, and Dr. Jeppesen responded that yes, this is likely.
The most common treatment-emergent adverse events in the teduglutide and placebo groups were abdominal pain (31% vs. 23%), nausea (29% vs. 19%), and stoma complications (24% vs. 7%). Physicians should explain to teduglutide patients that abdominal discomfort resulting from growth of the bowel is to be expected, Dr. Jeppesen said.
Three patients discontinued teduglutide; the reasons were abdominal distention, abdominal pain, and investigator decision. Four patients discontinued placebo treatment. There were no deaths in the study.
Dr. Jeppesen disclosed consulting for the study sponsor, NPS Pharmaceuticals.