Boehringer Ingelheim has put a hold on its Phase I work with a BACE inhibitor for Alzheimer's, marking the latest in a series of missteps for this category of therapeutics, which has emerged as one of the key arenas in the field.
Boehringer's partner Vitae Pharmaceuticals ($VTAE), which recently went public, says that Boehringer--a private company--made the decision on the hold after observing skin rashes in patients enrolled in an early-stage dose-ranging study. Just last fall Vitae touted early signs that the BACE drug, which is designed to interfere with a cascade of events that creates toxic clusters of amyloid beta, was working as planned.
Shares of Vitae plunged about 20% after the news hit Thursday evening.
"Our partner is working diligently to evaluate and understand this observation," said Dr. Richard Gregg, the CSO of Fort Washington, PA-based Vitae. "We are confident that the analysis will result in a clear understanding of how to proceed with BI 1181181, and we remain committed to our partner and the BACE program. Depending on the outcome of the evaluation and Boehringer Ingelheim's decision, we expect that either BI 1181181 or its structurally distinct, Phase I-ready back up will be advanced, with the goal of delivering a medicine with disease-modifying benefits to patients suffering from Alzheimer's disease."
Vitae CEO Jeff Hatfield
Vitae CEO Jeff Hatfield told FierceBiotech last fall that investigators were looking for the right dose to lower amyloid beta, a hotly pursued theory that has engaged a lineup of biopharma companies following the Phase III failures of solanezumab (Eli Lilly) and bapineuzumab (Johnson & Johnson and Pfizer).
The potential payoff--if it works--would be enormous, which is one reason why so many developers are willing to invest in the field. AstraZeneca ($AZN) estimated its BACE program could earn up to $5 billion a year--just before it licensed out rights to Eli Lilly ($LLY) for an upfront fee that amounted to 1% of that figure.
Off-target toxicity was the likely culprit behind the death of Eli Lilly's BACE program for LY2886721. That failure pushed Lilly to ink a $500 million deal--$50 million upfront--with AstraZeneca to take charge of its BACE drug, AZD3293. Roche ($RHHBY) also killed off an early-stage effort, though it has yet to attempt to explain why. Astellas, meanwhile, backed out of its $760 million deal with CoMentis on another early-stage BACE drug.
Merck ($MRK), meanwhile, has emerged as the leader in the BACE race, accelerating a late-stage study of its own BACE drug--MK-8931--after clearing a safety hurdle in the clinic. Biogen Idec ($BIIB) recently partnered with Eisai on E2609. And Novartis ($NVS) is positioning its own BACE inhibitor for the clinic, targeting presymptomatic patients.