Amgen’s Arrowhead deal sets up RNAi battle


Amgen’s agreement with the RNA interference specialist Arrowhead Pharmaceuticals will see it develop two RNAi therapies for cardiovascular disease, putting it on track for a showdown with The Medicines Company.

The Medicines Company and its partner Alnylam are currently ahead with their PCSK9-targeting RNAi project, which is due to report phase II results at the AHA meeting in November. Whether the groups can fund a large cardiovascular outcomes study is another matter, and this might give Amgen a chance to catch up.

For now, though, both programmes covered by the Amgen-Arrowhead agreement are preclinical, so the companies have a way to go. One of the projects, ARC-LPA, targets lipoprotein(a), a cardiovascular disease risk factor that is independent of cholesterol and LDL levels.


Meanwhile, the target of the other programme remains undisclosed. It is possible that this could be PCSK9, Leerink analysts wrote, but Amgen and Arrowhead are keeping quiet for now. The latter’s chief executive Chris Anzalone dropped several clues on a conference call, however, including saying that the target originated at Amgen rather than within Arrowhead.

PCSK9 would make sense – Amgen could be shoring up its franchise against PCSK9 RNAi candidates, which could have the advantage of once-quarterly dosing compared with every two weeks for the existing PCSK9 drugs, Repatha and Sanofi/Regeneron’s Praluent.

Repatha’s 2022 forecast is around $4bn, according to EvaluatePharma consensus forecasts, but this could be eroded should the RNAi approach prove to be a success. Uptake of PCSK9 drugs has already proven somewhat disappointing.

As well as possibly giving it access to a next-generation PCSK9-inhibiting approach, the deal with Arrowhead also provides Amgen with a potentially complementary product with the ARC-LPA platform. Existing hyperlipidaemia therapies do not bring lipoprotein(a) levels down, according to Arrowhead’s chief operating officer Bruce Given. “This is a matter of parallel play. A completely new front is being opened up against cardiovascular disease.”

Mr Anzalone added that it would be Amgen’s decision whether to study ARC-LPA in combination with Repatha, but did not seem to rule out the possibility.

The Arrowhead executives were also reluctant to say when clinical development of an ARC-LPA candidate might begin, but when pressed Mr Given said an IND application in either 2017 or 2018 was “not impossible”.

Arrowhead is yet to start work on the project with the undisclosed target, so that seems likely to be further behind.


The agreement, which gives Amgen a worldwide exclusive licence to the ARC-LPA programme, and an option for the same for the undisclosed project, is worth up to $673.5m, but as is customary with these types of deals it is heavily back-end loaded.

Mr Anzalone nonetheless described the up-front fee of $56.5m – made up of $35m in cash and $21.5m in the form of an equity investment – as “substantial for a company of our size”, particularly for preclinical assets.

The deal comes just over a year after another Amgen acquisition in the cardiovascular space, that of Dezima Pharma for $300m up front, which gave it the CETP inhibitor TA-8995 (Amgen doesn’t buy Esperion, September 17, 2015). 

The RNAi space has had its fair share of setbacks, but Amgen’s deal with Arrowhead could be a sign of a renaissance. The upcoming results with The Medicines Company’s candidate will be another indication of whether targeting RNAi could work in cardiovascular disease – and whether Amgen has made a good bet or not.

Project Study Trial ID Data due
ALN-PCSsc/PCSK9si Orion NCT02597127 Nov 2016

To contact the writer of this story email Madeleine Armstrong in London at or follow @medtech_ma on Twitter

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