The U.S. Food and Drug Administration (FDA) has granted an orphan drug designation to glepaglutide for the treatment of the short bowel syndrome (SBS). Glepaglutide is a long-acting glucagon-like peptide-2 (GLP-2) analog currently in development by Zealand Pharma A/S.
SBS is a rare, permanent condition in which patients have lost part of the short bowel; usually as a result of surgery for another condition (i.e., Crohn's disease, ischemia, radiation damage). As a result of the shorter GI tract, patients with the condition have debilitating diarrhea, malnutrition, dehydration and fluid/salt imbalances.
Patients with SBS are required to follow a relatively strict diet comprised of many small meals each day and often need parenteral feeding to get their required nutrients.
In 2012, Gattex
(teduglutide), also a GLP-2, was approved by the FDA. Other drugs in development to treat short bowel syndrome include crofelemer, NB100, melatonin, human insulin, docosahexaenoic acid, and PV802.
Earlier this year, the company announced
its phase 2 clinical trial met its primary endpoint (reduction in wet weight fecal output as a measure of patients' intestinal absorptive capacity). In that study, 16 SBS patients were tested on 2 of 3 glepaglutide doses (10 mg, 1 mg and 0.1 mg). The first dose was given over a 3-week period, followed by a 4-week washout period and then the second dose was administered for a further 3 weeks.
Glepaglutide successfully met the primary study endpoint of reducing fecal wet weight output in the 2 higher doses showing reductions of 833 grams/day (P
= .0002) and 593 grams/day (P
= .0021) in the 10 mg and 1 mg dose groups, respectively.
Pharmacokinetic analysis confirmed that daily dosing is sufficient to sustain efficacy. Gattex is also administered once a day.
The most frequently reported adverse events (AEs) were nausea, abdominal pain, abdominal distension, vomiting, stoma complications, dizziness, polyuria, decreased appetite, peripheral edema, cough and injection site reactions. Most adverse events were mild to moderate in severity.
Following meetings with U.S. and EU regulatory authorities, the company has stated its intentions to begin Phase 3 clinical trials in 2018.
In a news release
, Britt Meelby Jensen, President and CEO of Zealand, said:
"The orphan drug designation is great news, both for Zealand and for the patients suffering from short bowel syndrome. The orphan drug designation for glepaglutide enables us to have a closer and more frequent dialogue with the FDA throughout our late stage clinical development. Glepaglutide is one of Zealand's leading product candidates, which we are developing all the way to market, and this designation is an important step for us in our efforts to ensure an efficient path to registration and patient access."
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