BioWorld International Correspondent

Biovitrum AB, the Swedish drug development firm spun out of Pharmacia Corp., entered one of Europe's landmark biotechnology deals of 2003, a pact with Amgen Inc. to develop small-molecule, selective inhibitors of 11beta-hydroxysteroid dehydrogenase 1 for Type II diabetes and other metabolic diseases.

The most advanced compound covered by the agreement, BVT.3498, is undergoing a Phase IIa clinical trial in Type II diabetes. (See BioWorld International, March 26, 2003.)

Biovitrum CEO Mats Petterson told BioWorld International that Amgen beat out "intense competition" from the "largest pharmaceutical companies in the world" to land the deal. Even though Amgen does not have a background in diabetes therapy and is only a recent convert to the attractions of small-molecule drugs, other key factors weighed more heavily in Biovitrum's reckoning. "What we find [in Amgen] is an extremely ambitious, visionary company," Petterson said.

The multifaceted alliance includes an up-front payment of US$86.5 million plus research fees, payable over three years. Stockholm-based Biovitrum also will garner money through co-promotion rights in the European Union or the Nordic region for selected Amgen products, plus additional fees for carrying out biopharmaceutical process development work on behalf of Amgen. And it would earn additional milestone payments worth up to US$435 million should products for two indications reach the market. It also would gain tiered royalty payments.

The agreement covers North and South America, the Europe Union, Australia and New Zealand. Amgen, of Thousand Oaks, Calif., will take on all development and commercialization activities in those regions. Biovitrum has retained rights for Japan and other Asian markets.

Petterson has repeatedly referred to Biovitrum's 11beta-11b-HSD1 inhibitor program as the company's "jewel in the crown." The structure of the agreement reflects that view. "We wanted a fairly broad collaboration because we knew there was a lot of value in this compound," he said.

Its access to part of Amgen's product portfolio will assist its own efforts to build an in-house sales and marketing organization. Biovitrum has gained EU co-promotion rights for Amgen's rheumatoid arthritis treatment Kineret (anakinra), as well as Nordic co-promotion rights for the investigational compounds cinacalcet hydrochloride and palifermin, which are in development for treatment of certain hyperparathyroid conditions and chemotherapy-related inflammations of the mouth, respectively. The company will also have Nordic co-promotion rights for any products resulting from the alliance.

The enzyme 11beta-11b-HSD1, which plays a key role in glucose metabolism by converting cortisone to the active glucocorticoid hormone cortisol, has attracted increasing attention as a drug target following research in animal models indicating a direct association with diabetes. Transgenic rats with elevated levels of the enzyme exhibited excessive levels of visceral fat, insulin resistance, diabetes and disordered lipid metabolism.

Recruitment into the placebo-controlled, double-blind Phase II trial of BVT.3498 suffered a dip during the summer months, Petterson said, but has picked up again recently. "We are quite confident we will be able to finish the study around year-end," he said. After that, the company will consider its options with respect to an initial public offering - "sometime next year, depending on the market situation." Biovitrum already is one of the best-funded biotechnology companies in Europe. Even before the present deal, it had US$100 million in cash.