BioWorld International Correspondent

Gastrotech Pharma A/S in-licensed from Eli Lilly & Co. a glucagon-like peptide 1 (GLP-1) analogue in development for treating pain associated with irritable bowel syndrome (IBS).

The compound, a peptide called GTP-010, had been the subject of a collaboration the two companies entered in 2004. Indianapolis-based Lilly owned the molecule but Copenhagen, Denmark-based Gastrotech Pharma had gained rights to its use in IBS through its purchase of intellectual property assets from bankrupt firm Melacure Therapeutics AB, of Uppsala, Sweden.

GTP-010 attained the primary endpoint in a 100-patient multicenter Phase II clinical trial by reducing pain by more than 50 percent of the maximum possible pain relief. "The response rate in the treatment groups is twice that of the placebo [group]," Gastrotech Chairman Hans Schambye told BioWorld International.

It also met secondary endpoints, based on duration of pain and pain relief response, on pain intensity and on global treatment measures. "All the secondary endpoints were met with very low p values," Schambye said.

The deal has taken around a year to negotiate. Terms were not disclosed, but Indianapolis-based Lilly is taking a minority equity stake in Gastrotech and would receive royalties on sales of GTP-010 should it undergo successful commercialization.

GLP-1 is one of three incretin hormones that are released following ingestion of food. Lilly, along with partner San Diego-based Amylin Pharmaceuticals Inc., is already marketing one GLP-1 analogue, Byetta (exenatide), as an adjunctive therapy for improving blood sugar control in patients with Type II diabetes.

Its mode of action in that indication is based on several effects, including its enhancement of glucose-dependent secretion by the pancreas, its suppression of excessive glucagon secretion and its slowing of gastric emptying.

GTP-010 acts on the same receptor but is "completely independent" of Byetta, Schambye said. The latter was derived from a peptide isolated from the Gila monster lizard species Heloderma suspectum, and has about 60 percent homology with the human GLP-1.

GTP-010, in contrast, has about 97 percent homology with human GLP-1, Schambye said, although it has been modified to extend its half-life. Even so, it is eliminated more quickly than Byetta. The latter needs to work for 24 hours, he said, whereas GTP-010 can be eliminated after an acute IBS episode.

Byetta is associated with nausea, vomiting and diarrhea. Postmarketing cases of acute pancreatitis have also been reported in patients on the drug. "We saw the nausea that you would expect in GLP-1, especially in the high-dose group, but otherwise we didn't see anything else," Schambye said.

IBS is responsible for large numbers of patient-to-GP and gastroenterologist visits every year. "It suffers from the fact that physicians do not have a treatment option. Patients are sent home and asked to take care of themselves," he said.

In IBS, the role of GTP-010 is based on correcting aberrant intestinal motility, thought to be a major cause of pain in IBS.

As GTP-010 requires delivery via subcutaneous injection, developing it for IBS patients will be "a challenge," Schambye said. "We will be reserving the treatment for severely affected patients because those are the ones who will accept an injection." A severe case of IBS consists of several attacks per week at least 12 weeks of every year - and there are some 3 million IBS patients in the U.S. in that category, he said.

Gastrotech plans to move GTP-010 into a Phase IIb trial later this year. It intends to undertake the study under its own resources, while keeping an eye out for potential partners. It also is seeking financing to fund the upcoming study.

"We hope to be able to announce something soon about financing," Schambye said. It will investigate the compound's potential in functional dyspepsia, another gastrointestinal condition associated with pain.