Amgen strikes $674M cardiovascular RNAi pact with Arrowhead

Amgen ($AMGN) has handed over an initial $56.5 million and committed to up to $617 million more to buy into Arrowhead Pharmaceuticals’ ($ARWR) efforts to aim RNAi therapies at cardiovascular targets. The deal gives Amgen the global license to a lipoprotein(a)-focused program and an exclusive option to pick up the rights to another therapy against an undisclosed cardiovascular target.

In return, Arrowhead is pocketing $35 million upfront and a $21.5 million equity investment. Amgen is also on the hook for up to $617 million in option payments and milestones, plus low-double-digit royalties on the lipoprotein(a) drug and single-digit royalties on the other, as-yet-unlicensed RNAi program. Arrowhead also gains a partner that knows what it takes to bring cardiovascular drugs to market, and the lustre that comes from having a Big Biopharma back its nascent delivery platform.

“We think [the deal] represents an important point of validation for our underlying RNAi-based platform technologies,” an Arrowhead spokesperson told FierceBiotech.

ARC-LPA, the lipoprotein(a)-focused drug, and the undisclosed program are the first candidates in Arrowhead’s pipeline to make use of its subcutaneous delivery platform, a technology the RNAi specialist thinks could open up a route of administration favored by physicians and patients. To date, Arrowhead has only generated preclinical data to back up its belief in the platform, but that has proven sufficiently compelling to prompt Amgen to write a check.

In May, Arrowhead presented data on ARC-LPA in transgenic mice and cynomolgus monkeys. The study showed a single dose of the drug triggered knockdown of upward of 98% in mice. And that lipoprotein(a) levels in monkeys were still down 75% 6 weeks after the final dose, adding to Arrowhead’s belief that its technology can have a pronounced, sustained effect.

Amgen is inclined to agree. "Arrowhead demonstrated a robust preclinical package for a siRNA against [lipoprotein(a)]," a spokesperson for the Big Biotech said. "RNAi has matured, and with Amgen’s advances in discovery research, we see an opportunity to leverage the expertise of Arrowhead to potentially target evolving novel targets."

The interest in lipoprotein(a) stems from its association to a person’s risk of cardiovascular disease, regardless of the individual’s levels of LDL. As such, while a physician can lower a patient’s LDL using statins, newer drugs such as Amgen’s PCSK9 inhibitor and lifestyle changes, a patient will still carry a higher risk of cardiovascular disease if lipoprotein(a) remains elevated.

Arrowhead’s answer is an RNAi trigger and accompanying delivery polymer designed to get into cells and cause knockdown of target gene expression. In the case of ARC-LPA, the goal is to cut production of apolipoprotein(a), one of the building blocks that make up lipoprotein(a).

Amgen’s willingness to buy into the idea represents a boost for Arrowhead and the broader RNA sector, enthusiasm for which has waxed and waned over the past decade. In the early years of the 21st century, Merck ($MRK), Novartis ($NVS), Roche ($RHHBY) and other leading lights of biopharma plowed into the field, only to cut back when the potential of the approach butted up against some persistent technical challenges.

Throughout the peaks and troughs in Big Pharma interest in RNA, the likes of Arrowhead and Alnylam ($ALNY) have continued to beaver away, advancing the technology and their pipelines to the point that they are once again catching the attention of their larger peers. Johnson & Johnson ($JNJ), Roche, Sanofi ($SNY) and others have bought their way back into the field in recent years.

Now, Amgen has joined the party, giving its cardiovascular franchise another avenue to explore while delivering a boost to Arrowhead as it enters a busy period for its in-house pipeline.

“We plan to release data on ARC-AAT before the end of the year, and potentially have multiple data readouts for ARC-520 and ARC-521 during 2017. We also intend to bring additional candidates into the clinic in 2017,” the spokesperson said.