AstraZeneca, Eli Lilly move closely watched BACE Alzheimer's trial

After a series of large late-stage setbacks in Alzheimer's in recent years, AstraZeneca ($AZN) and research partner Eli Lilly ($LLY) have had a glimmer of good news after their BACE inhibitor AZD3293 passed a safety analysis and will now move into the final stages of testing.

Today, both AstraZeneca and Lilly released a joint statement saying that the independent data monitoring committee recommended the study continue without modification. The analysis was not however designed to review efficacy.

Lilly has a 50/50 stake in the drug, taking a lead role on research back in 2014 after paying $50 million in a collaboration package worth a total of up to $500 million as AstraZeneca looked to limit its work on Alzheimer's.

Both companies will now begin Phase III testing for AZD3293, under the study name Daybreak, triggering a $100 million milestone payment from Lilly to AstraZeneca. They will begin enrolling participants in the third quarter of 2016, according to their statement.

Menelas Pangalos, executive VP of the IMED Biotech Unit at AstraZeneca, said: "Alzheimer's disease remains one of the biggest challenges facing medical science today. BACE inhibitors have the potential to target one of the key drivers of disease progression and we are delighted that our combined efforts have resulted in the development of AZD3293 moving into the next phase of study. Disease modifying approaches, such as this, have the potential to transform the treatment of Alzheimer's disease and help patients in this area of large unmet medical need."

Lilly is continuing to push on in Alzheimer's despite some notable setbacks, including dumping its own BACE program for the disease--the drug LY2886721--after investigators linked it to toxicity in liver tests.

In 2012 Lilly famously--though reluctantly--conceded that its Phase III study for solanezumab was a failure, forcing it to go back to the drawing board to redesign a new Phase III approach tailored to early-stage patients.

And that flop followed the failure of Lilly's semagacestat, a gamma-secretase therapy that harmed patients who took it.

More recently, the U.S. company also moved the goalposts for a new solanezumab trial over its fears it would fail a third time, and came under fire from critics for potentially lowering the bar on efficacy for a new class of Alzheimer's drugs. Overall clinical trial failure rates in Alzheimer's have been estimated as high as 99% in the past decade.

Over the past few years, BACE has become a central R&D focus in later-stage Alzheimer's studies. Merck ($MRK) has the leading program in the clinic with its MK-8931 in late-stage testing, though Roche ($RHHBY) scrapped an early-stage effort of its own without ever explaining why.

Biogen ($BIIB) recently partnered with Eisai on E2609, while Novartis ($NVS) is positioning its own BACE inhibitor for the clinic, targeting presymptomatic patients. After AZD3293 has passed its safety analysis, this will likely also be a boost to all of those remaining in the BACE race.

But as always with this disease, there are problems. There was a big setback in the field in February when Boehringer Ingelheim and its biotech partner Vitae Pharmaceuticals ($VTAE) put a hold on their Phase I work with a BACE inhibitor. The decision was made after observing skin rashes in patients enrolled in an early-stage dose-ranging study.

The potential role of BACE inhibition in controlling the disease centers on the notion that eliminating toxic loads of amyloid beta in the brain will slow or stop the disease. AZD3293 has been shown in Phase I studies to reduce levels of amyloid beta in the cerebrospinal fluid of people with Alzheimer's disease and healthy volunteers.

Some investigators fear however that a BACE strategy could also interfere with myelin, which would present a serious threat to anyone taking the drug. And not everyone believes that amyloid beta should be the actual target, with a second theory based around Tau protein tangles splitting research camps into two.

But if these safety concerns are dealt with, analysts estimate AstraZeneca and Lilly's BACE program could earn up to $5 billion or more a year, given that there are so few treatments on the market. Currently, 46 million people globally are estimated to have the memory-destroying disease.

Pfizer had also been developing a new Alzheimer's drug, known as "bapi," with research partner Janssen ($JNJ) but in 2012 decided to kill off the Phase III program after two late-stage trials ended in failure.

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