31 Oct 2014

Vitae Pharmaceuticals' BACE inhibitor, VTP-37948, lowered cerebrospinal fluid Aβ by up to 80 percent in healthy volunteers, according to topline data from a Phase 1 clinical trial. A second Phase 1 trial that used a single-ascending-dose strategy suggested that volunteers tolerated the drug well. Vitae chief scientific officer Richard Gregg told Alzforum that the companies will soon test the inhibitor in multiple rising dose trials. Results should be available early next year, said Vitae CEO Jeffrey Hatfield. The company will develop the inhibitor, also known as BI 1181181, in partnership with Boehringer Ingelheim.

Vitae used a structure-based approach to develop the drug, which fits the catalytic pocket of the aspartyl protease. VTP-37948 joins BACE inhibitors being developed by other pharmaceutical companies including Merck, AstraZeneca/Lilly, and Novartis. The Vitae inhibitor, like the other compounds under development, does not discriminate between β-secretase isoforms, blocking both BACE1 and 2. That, plus the growing list of substrates cleaved by the secretases, has led some researchers to advise caution in the development of these drugs (see Dec 2013 conference news). Hatfield emphasized that full inhibition of BACE may not be needed to lower Aβ in the brain. "The jury is still out on how much inhibition is required. It could be as low as 15 percent," he told Alzforum. For more information see Vitae's press release.—Tom Fagan