The 12 members of the US Food and Drug Administration (FDA) Gastrointestinal Drugs Advisory Committee (GIDAC) yesterday voted unanimously that teduglutide (Gattex, NPS Pharmaceuticals) should be approved for the treatment of adults with short bowel syndrome (SBS).
If approved by the FDA, teduglutide, an analog of GLP-2, a protein involved with intestinal growth and function, will be the first targeted therapy for SBS and will provide a much-needed alternative to intravenous parenteral nutrition, which is the current, cumbersome treatment for this condition.
Teduglutide, which is given as a subcutaneous injection, has been granted orphan drug status by the FDA. It is estimated that there are from 10,000 to 15,000 adult patients with SBS in the United States.
The safety concerns that emerged from the clinical trials with teduglutide, including its potential for promoting tumors, intestinal obstruction, cholecystitis, and pancreatitis, did not worry the FDA or the panel.
There were 3 cancer deaths among patients treated with teduglutide: 2 from lung cancer and 1 from a metastatic adenocarcinoma.
However, the deaths from lung cancer occurred in patients who were heavy smokers, and the death from adenocarcinoma occurred in a patient who had been previously diagnosed with Hodgkin's disease and who had an enlarged liver with a focal lesion before treatment.
"The relationship with malignancy cannot be completely ruled out at this time, and we suggest warning patients that Gattex may accelerate the growth of malignancy and increase the risk of malignancy," John Troiani, MD, PhD, from the FDA's Center for Drug Evaluation and Research, said in his presentation to the panel. "Still, in these studies, all patients who died were at risk because they were either smokers or had a liver lesion prior to treatment."
As for the other safety issues, "they occur in this population anyway," he said.
The panel said the risk evaluation and mitigation strategy that the manufacturer proposed was adequate to address these safety issues.
Craig Earle, MD, from the University of Toronto, Ontario, Canada, said the tumor-promoting concerns could be dealt with through careful monitoring and long-term follow-up.
"These patients need to be followed for at least 10 years with regard to colon cancer. With regard to small bowel disease, I would be hesitant to recommend routine screening," he said.
William K. Kelly, DO, from Thomas Jefferson University, Philadelphia, Pennsylvania, agreed. "Teduglutide appears to be safe, but we need to follow patients for longer — more than 7 years and up to 10 years. Also, we need to ask if there are other sites that can be affected, other than the gastrointestinal tract."
The panel members were impressed by the fact that treatment with teduglutide resulted in a number of patients being able to go without parenteral treatment for 3 or more days.
Fifteen patients were able to be weaned from intravenous parenteral treatment completely.
"I found those results very impressive. The fact that more than 40% could forego parenteral treatment for a day,...25% could go without for 3 or more days, and 15 patients could be weaned completely — very noteworthy," said Elaine Morrato, DrPH, MPH, from the University of Colorado in Aurora.
Elizabeth Tucker, from Lakeville, Minnesota, who was the patient representative on the panel, said, "I'm on [total parenteral nutrition] and I manage quite well, but having the prospect of such an option is a wonderful thing."
Medscape Medical News © 2012 WebMD, LLC
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Cite this: FDA Panel Endorses Teduglutide for Short Bowel Syndrome - Medscape - Oct 17, 2012.