Assistant Managing Editor

A day after reporting positive Phase III data with a weekly version of glucagon-like peptide-1 agonist exenatide, partners Amylin Pharmaceuticals Inc. and Eli Lilly and Co. entered a collaboration with Atlanta-based Altea Therapeutics Corp. for a transdermal version of the drug using Altea's PassPort Transdermal Delivery System.

The companies began collaborating earlier "with some feasibility work," said Steven Damon, senior vice president of business development at Altea, with the goal of developing a product that could deliver exenatide via more convenient administration compared to injections.

The successful completion of a recent Phase I study of the exenatide transdermal patch in Type II diabetes patients helped seal the formal development and commercialization deal.

Amylin and Lilly, which already market exenatide as a twice-daily injection formulation under the brand Byetta, agreed to make an undisclosed up-front cash payment to Altea, in addition to an equity investment. On top of that, Altea is eligible for clinical, regulatory and development milestones of up to $46 million, plus royalties on future product sales.

Perhaps best of all, Amylin and Lilly are picking up the tab for all development costs, a definite advantage to a small firm like Altea, which will continue offering its input during the development process.

"They're experts in diabetes and diabetes management, and we're the experts in transdermal drug delivery," Damon told BioWorld Today.

Altea's PassPort technology is designed to overcome some of the limitations of conventional transdermal delivery systems, which work well for lipid-soluble drugs with low molecular weight but have proved ineffective in delivering larger or peptide-based drugs. The technology involves the use of a small, reusable applicator that's designed to do two things: "One, it prepares the skin for delivery of the drug, in this case exenatide," Damon said. "And, two, it attaches the patch to the skin" for sustained drug delivery.

In preparing the skin for delivery, the PassPort system creates multiple tiny aqueous channels through the stratum corneum, the outer dead surface layer of skin that acts as a barrier to therapeutic delivery. The application is designed for once-a-day administration and is a "painless and sensationless process," Damon added.

The obvious benefit of transdermal delivery is that it could increase patient compliance by eliminating injections. That type of noninvasive approach is something for which diabetics in particular have clamored, since they face frequent injections of insulin or other drugs to manage their disease.

That was the aim of several inhaled insulin programs, such as Exubera, from New York-based Pfizer Inc. and San Carlos, Calif.-based Nektar Therapeutics Inc., which had the makings of a blockbuster product but was dropped due to lagging sales. Similar programs from Lilly and Alkermes Inc. and from Bagsvaerd, Denmark-based Novo Nordisk AS and Hayward, Calif.-based Aradigm Corp. also fell by the wayside.

Only MannKind Corp., of Valencia, Calif., was left standing. That firm, which reported positive results from a Phase III program of its inhaled insulin product Afresa (insulin monomer human [rDNA] origin) late last year, submitted a new drug application for use in Type I and Type II diabetes patients last month. (See BioWorld Today, Dec. 5, 2008.)

To date, inhaled insulin has not done well, largely because of the unwieldy devices, like the one for administering Exubera. "There was all that promise, but it wasn't as convenient as patients and physicians had hoped," Damon said.

Altea has in its pipeline a product for the transdermal delivery of insulin for Type I and Type II diabetics, and early studies have demonstrated sustained steady basal levels of insulin.

Transdermal exenatide will be Altea's second diabetes product.

Exenatide, which gained approval as Byetta in 2005, is targeted as an adjunctive therapy to improve blood sugar control in Type II diabetes patients who have not achieved adequate control on common diabetes medications, metformin and sulfonylurea. U.S. sales of the drug totaled $163 million for the fourth quarter, though Byetta faces near-term competition from Novo Nordisk's once-daily GLP-1 inhibitor liraglutide, which is under FDA review, with an advisory panel scheduled for today.

San Diego-based Amylin and Indianapolis-based Lilly also are working in a separate deal with Alkermes Inc., of Cambridge, Mass., on the once-weekly exenatide. That product yielded promising data earlier this week, showing statistical significance in controlling glucose and weight loss over current medications in a Phase III trial. (See BioWorld Today, April 1, 2009.)

Now that a formal deal is in place for the transdermal version of the product, the plan is to "go full speed ahead to get the product to market as soon as possible," Altea's Damon said.

In addition to its diabetes programs, Altea also is working on a patch, as well as on an undisclosed program in a potential $109 million deal signed with Lake Forest, Ill.-based Hospira Inc. in July.

News of the deal sent shares of Amylin (NASDAQ:AMLN) up 30 cents to close Wednesday at $12.05.