Amgen’s cautious bet on the beta amyloid hypothesis

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We might still just about be in a biotech bull market in which Alzheimer’s disease has enjoyed a resurgence of popularity, but it still helps to have the considerable risk of a neuroscience project borne by multiple large players – at least in principle.

A case in point is Amgen and Novartis, which yesterday did something akin to an asset swap that will see the risk of some of each company’s central nervous system projects being shared. Still, look beneath the surface and it is clear that the most important part of the tie-up involves Amgen buying into Alzheimer’s disease.

After all, it is Amgen that is paying Novartis an undisclosed up-front licence fee and taking on a disproportionate share of R&D costs, as well as throwing a far more advanced migraine asset into the mix. In return Amgen basically gets to share rights to Novartis’s CNP520, a beta secretase (BACE) inhibitor that only appeared on the Swiss group’s R&D list in July.

BACE is an enzyme that cleaves amyloid precursor protein and creates beta amyloid; Amgen has thus seen the logic of buying into the highly risky and largely unproven beta amyloid hypothesis. For its part the big biotech group says it was the first to clone the BACE gene, and subsequently validated the target via Decode Genetics, the Icelandic business it bought in 2012.

Though Amgen has not previously revealed any in-house leads against this target it says it might put some of its own BACE projects into the deal. Novartis says CNP520 is in a phase I/II study, but no entry exists detailing any clinical trials of this molecule on Clinicaltrials.gov.

Migraine sideline

In addition to providing financing, Amgen is giving Novartis commercial rights outside North America and Japan to two of its migraine assets – AMG 334 and AMG 304. AMG 334, an anti-CGRP MAb, posted promising phase II migraine prevention data in May, and is now in phase III.

However, this is a crowded space, with Alder Pharmaceuticals’ ALD403, Lilly’s LY2951742 and Teva’s TEV-48125 – all acting on CGRP – hot on Amgen’s tail (IHS – Migraine rides to Alder’s rescue, May 18, 2015). Amgen giving up part of this phase III project plus some cash in return for an early Alzheimer’s asset is not much of a vote of confidence in AMG 334.

Not that Alzheimer’s is devoid of competition, of course, though what this space lacks is clinical trial success. There has been a flurry of renewed interest in the beta amyloid hypothesis, and Astellas, Johnson & Johnson, Biogen, Merck & Co and Lilly all boast BACE inhibitors more advanced than CNP520 (Alzheimer's just BACE instinct for Astra and Lilly, December 1, 2014).

Interestingly, the Amgen tie-up does not explicitly include Novartis’s sole other Alzheimer’s project, the beta amyloid active immunotherapy CAD106, which the Swiss group recently bought from its distressed originator, Cytos Biotechnology, for SwFr4m ($4m).

One of the first moves with CNP520 will be to include it in the Banner Alzheimer's Institute’s broad study investigating the risk of developing the disease. Banner, a non-profit organisation based in Arizona, is the leading force behind the Alzheimer’s Prevention Initiative, a global project to which Novartis signed up a year ago.

At one point it was thought that government-funded academic groups like Banner – which did not risk losing face with investors – were the only ones still brave enough to undertake serious Alzheimer’s research. Amgen just showed that this is no longer the case.

To contact the writer of this story email Jacob Plieth in London at jacobp@epvantage.com or follow @JacobPlieth on Twitter

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