About Actelion’s Renin Inhibition Program

Since the early 1980s, the pharmaceutical industry has been actively searching for suitable renin inhibitors. While prototypical renin inhibitors had been identified, they all shared a common flaw in having a limited bioavailability on oral administration. Most major pharmaceutical companies abandoned their efforts in the field in the mid-1990s.

Actelion's research team initiated a new program starting from new small molecules with good oral absorption but weak renin inhibitor activity. After several years of compound optimization, Actelion arrived at potent, orally active renin inhibitors with significantly improved oral bioavailability. Actelion believes that a number of these compounds may be suitable for clinical development and have protected our renin inhibitors with numerous patent applications.

Actelion and Merck & Co., Inc. formed an exclusive worldwide alliance in December 2003 to discover, develop and market new classes of orally available renin inhibitors for patients suffering from cardio-renal diseases. Until now Actelion has received a total of USD 47 million as part of a series of upfront, research and development milestones. Potential additional development and approval milestones of up to USD 225 million are envisioned for the successful commercialization of the first collaborative product.

Current Status

Achieving it’s forth milestone, the renin alliance has commenced dosing in a Phase II program for its first compound, a new renin inhibitor for the treatment of hypertension. The two companies will jointly fund Phase II development, with Merck responsible for funding all Phase III and outcome studies. Merck will lead and fund commercialization. Actelion retains a worldwide option to co-promote any product resulting from this alliance as a paid-for sales force.

Supporting Studies

In July 2006, the alliance entered its first compound - which demonstrated good bioavailability in animal models - into man. A series of Phase I studies including pharmacokinetics and pharmacodynamics have been performed. In addition, studies to evaluate the interactions with other drugs were initiated and/or completed.