Boehringer, Vitae survive first clinical challenge in a crowded Alzheimer's race

Boehringer Ingelheim and its biotech partner Vitae Pharmaceuticals ($VTAE) have survived the first challenge in the crowded race to develop a BACE inhibitor for Alzheimer's disease. The newly public Vitae reported after the market closed on Thursday that the oral BI1181181/VTP-37948 hit the goal posts on a key biomarker for BACE, or beta secretase, flushing a prime suspect behind the disease without triggering any red safety flags in a pair of Phase I studies among a small group of healthy volunteers.

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Phase I is not a huge hurdle, but it is an important one for these two companies. BACE has emerged as the big target among a group of biopharmas jockeying for a position in this market, which will deliver blockbuster sales for any candidate that can survive a dangerous development path littered with the wreckage of dozens of past failures. The big idea here is that a drug that can clear toxic clumps of amyloid beta can reduce the risk of developing the disease, and investigators credited this particular therapy with lowering the level of amyloid beta in cerebral spinal fluid by up to 80%.

The plan now at Boehringer Ingelheim is to push on with new Phase I trials, including a dose-ranging effort to find the right level for bigger human studies.

Vitae CEO Jeff Hatfield

This field has been incredibly challenging, with no clear agreement on what causes the memory-stealing disease or exactly how it can be stopped. And there's a tremendous amount of work that has to be done, notes Vitae CEO Jeff Hatfield, including just what is the right amount of drug that will be needed.

"What we don't know is how much amyloid-beta lowering is the right number and what should we be shooting for," he says.

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But if BACE is the right approach, this oral drug offers a chance to hit more of the potential targets for the disease as well as a much easier route of administration than more advanced biologics now in the clinic.

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 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 ($LLY) BACE program for LY2886721. That failure, one in a series of setbacks for the pharma giant in Alzheimer's, 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 recently 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 pre-symptomatic patients.

If any of those drugs prove valuable in delaying or stopping Alzheimer's, "it could be the best selling drug in the world," says Hatfield.

Investors aren't ready to be early believers, though, after all the earlier failures, including Phase III setbacks for solanezumab and bapineuzumab, which also tested the amyloid beta theory. When Fort Washington, PA-based Vitae recently went public, the company had to accept a deep discount on its share price to complete the IPO, selling shares at $8.

"I think that there remains an appetite for investing in companies," says the CEO. "And there are companies not getting out." As the end of the year approaches, he says, more and more investment groups will be locking in their performance for the year, making the market even more uncertain.

"It will take a more and more unique story to get on the list," he adds. "The marketplace is so volatile," the final IPO price can vary dramatically depending on which day you price. "It's a bit of a lottery."

- here's the release

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