FDA rejects Zealand Pharma's GLP-2 analog in rare bowel disease

The FDA has denied Zealand Pharma’s approval bid for glepaglutide—a possible challenger to Takeda’s Gattex—in short bowel syndrome (SBS), citing a lack of evidence.

In the FDA’s complete response letter, the agency recommended that the company run another clinical trial to provide more data for glepaglutide’s efficacy and safety, according to a Dec. 19 release from the Danish biotech.    

Zealand Pharma said it will continue discussions with the regulatory agency to establish a path toward U.S. approval, with plans to launch a single phase 3 trial set for next year. The additional trial is designed to generate more evidence for a FDA resubmission while also supporting regulatory requests for glepaglutide outside of the U.S. 

The biotech will proceed with ongoing plans for a European marketing authorization application submission in 2025, according to the release.

The investigational drug is a long-acting GLP-2 analog developed as a liquid that’s delivered via an autoinjector. The candidate is designed to eliminate IV dependency for SBS patients with intestinal failure.

The FDA submission was based on results from a placebo-controlled phase 3 registration trial dubbed EASE-1. A singular trial underpinning the regulatory request is not uncommon for a rare disease area such as SBS, according to Zealand Pharma.

The trial hit its primary endpoint, with twice-weekly doses of glepaglutide reducing weekly parenteral support volume by a statistically significant 5.13 liters at 24 weeks compared to baseline. That being said, once-weekly doses of glepaglutide failed to yield statistically significant reductions in parenteral support.

Zealand Pharma did not specify what dosage regimen was tied to the FDA approval request.

“We remain firm in our belief that glepaglutide provides a significant advance in GLP-2-based therapies for the potential treatment of SBS patients who are dependent on parenteral support,” Zealand Pharma Chief Medical Officer David Kendall, M.D., said in the Dec. 19 release. “We are committed to working with the agency to align on the path toward a regulatory approval so that we can bring glepaglutide to patients in the U.S.”

The candidate has snagged orphan drug designation from the FDA for treatment of SBS. If approved, the drug would go up against Takeda’s Gattex, another GLP-2 analog used by adults with SBS who are dependent on parenteral support for nutrition. The subcutaneous treatment is given every day, giving glepaglutide a potential convenience advantage over Takeda’s established therapy.