BioWorld International Correspondent

Zealand Pharmaceuticals A/S received a substantial boost with the news that its partner Sanofi-Aventis Group is planning to move its glucagon-like peptide 1 (GLP-1) agonist AVE0010 into a 3,000-patient Phase III clinical trial in Type II diabetes during the current quarter.

Paris-based Sanofi-Aventis said, while releasing its 2007 annual results, that it will evaluate a once-per-day injection of AVE0010 - previously known as ZP10 - in combination with existing treatments metformin, sulfonylurea and insulin and as a monotherapy. The study also will encompass a head-to-head comparison with exenatide (Byetta), a product that is marketed jointly by Indianapolis-based Eli Lilly & Co. and San Diego-based Amylin Pharmaceuticals Inc.

"It's very encouraging for us, obviously. It's the first program of ours moving into Phase III," Mogens Vang Rasmussen, interim CEO of Glostrup, Denmark-based Zealand Pharma told BioWorld International.

AVE0010 and Byetta are both analogues of a peptide called Exendin-4, which is isolated from the Gila monster lizard species Heloderma suspectum and is about 60 percent identical to the human peptide. They reduced elevated blood sugar levels by boosting insulin secretion. Zealand has modified its molecule to improve its stability and pharmacokinetics. Byetta is dosed twice per day, whereas AVE0010 requires just one daily dose. It may have a more favorable side effect profile as well.

The start of the study does not trigger a milestone payment, since Zealand received one on the completion of a Phase IIb study last September. It out-licensed the molecule, and a sustained-release successor, to Sanofi-Aventis (then Aventis) in 2003 in a deal comprising an up-front payment of $10 million, a further $100 million in milestones and royalties on product sales. So far it has secured just $15 million of the available milestones. "There are still $85 million to come," Rasmussen said.

The sustained-release version has completed a Phase I clinical trial and is due to enter a Phase II study in the first half of this year.

Sanofi-Aventis anticipates filing for approval for AVE0010 in 2010. The filing for the sustained-release version would follow two years later. The program was previously the subject of a joint venture between Zealand and Dublin, Ireland-based Elan Corp. The latter exited the program in March 2003, but retained a 13 percent share of Zealand's royalties.

Zealand has one other partnered product in the clinic, GAP-134/ZP1609, an oral gap junction modifier which it has out-licensed to Madison, N.J.-based Wyeth. It currently is undergoing a Phase I clinical trial as treatment for preventing atrial fibrillation after surgery. Its unpartnered clinical programs include ZP120, an agonist of opioid-receptor-like 1, which is undergoing a Phase II clinical trial in a blood pressure condition called isolated systolic hypertension. ZP1846 is a peptide treatment undergoing a Phase I study for treatment and prevention of chemotherapy-induced diarrhea. In addition, the company has several late-preclinical programs in obesity, osteoporosis and inflammatory bowel disease.

Privately held Zealand currently has about DKK240 million (US$47 million) in hand to progress those programs. "For these uncertain market times, we are in a rather nice position. We don't have our backs to the wall, Rasmussen said.