FDA advisory committee favors Gattex as treatment for short bowel syndrome

The FDA’s Gastrointestinal Drugs Advisory Committee today unanimously agreed that Gattex offers a clinical benefit that outweighs potential risks in patients with short bowel syndrome.

NPS Pharmaceuticals is seeking approval for Gattex (teduglutide), a recombinant analogue of glucagon-like peptide-2 (GLP-2), as a treatment for adults with short bowel syndrome (SBS) who require parenteral nutrition (PN). If approved, Gattex would be administered subcutaneously at a dosage is 0.05 mg/kg of body weight daily.

The company presented results from two 24-week, randomized, double blind trials. In the first trial, doses of 0.10 mg/kg and 0.05 mg/kg per day were compared with placebo, but response to the larger dose was not statistically significant. The second study only incorporated the 0.05 mg/kg/day dose and resulted in a 63% response rate for Gattex compared with 30% in the placebo group (P=.002) and a significant, 20% or larger reduction in PN/IV volume (P=.001 or less compared with placebo). More than half of participants (53.8%) experienced an additional 1 day or more off total parenteral nutrition (TPN), and 15 patients were eventually weaned off TPN.

When asked whether the benefit indicated by the study results was clinically meaningful, all committee members voted yes, with some noting that the number of patients weaned off TPN was more compelling than the PN/IV volume reduction. The committee also unanimously agreed that the benefits outweighed potential risks, but some indicated concern over the small study sample (n=173) and lack of long-term safety data.

“I think it is important to understand that absence of evidence is not evidence of absence,” said Atul Kumar, MD, assistant professor of medicine, Department of Veterans Affairs in Northport, N.Y. “My gut [feeling] is that this is a potentially safe drug ... [but] I think there have to be some mechanisms to ensure that there are no side effects.”

Observed adverse events during the trials were relatively few but included malignancies, intestinal polyps and obstructions and incidence of cholecystitis. Proposed labeling for Gattex included warnings for these conditions, as well as contraindications for malignancy or a history of malignancy. NPS Pharmaceuticals also plans to establish a patient registry upon approval for Gattex, intended to monitor the natural progression of SBS and provide long-term safety and efficacy data for Gattex within a large population. The committee indicated that safety monitoring as outlined by the proposed labeling would be sufficient. It also recommended clinical and laboratory surveillance and physical exams every 3 months, along with any other procedures as dictated by a patient’s clinical status.

Members also discussed the adequacy of the Risk Evaluation and Mitigation Strategy (REMS) program outlined by NPS Pharmaceuticals, which would include distribution of educational materials to health care providers and professional organizations, as well as patient safety information. The majority of members voted that the REMS as presented sufficiently addressed safety concerns (10 yes, 1 no, 1 abstention), and did not call for additional post-marketing studies pending approval.

“I don’t think we are proposing an efficacy study,” said Gagan Sood, MD, associate professor in the Medicine and Surgery Department at Baylor College of Medicine in Houston. “We’re all concerned about the side effects; about the potential for cancer. I don’t believe that we need a study, but a very comprehensive registry, where the documentation is well done.”