Updated: Roche pays Alnylam $310M cash to partner on RNAi candidate for heart disease

Roche is buying into a mid-stage cardiovascular drug candidate out of Alnylam’s RNAi platform in a deal that starts with $310 million upfront and could add up to $2.8 billion.

The two companies will co-develop and co-commercialize the program, zilebesiran, as a treatment of hypertension in patients with high cardiovascular risk and other heart diseases by lowering blood pressure.

In the US, the duo will split profits and losses equally, while Roche will take on ex-US sales and pay Alnylam a royalty in those regions. It also agreed to shoulder 60% of the development costs for the first indication, which will include an expensive cardiovascular outcomes trial prior to filing for approval. Alnylam will lead that joint effort.

Yvonne Greenstreet

That means they will have cardiovascular outcomes data in hand at launch, which Alnylam CEO Yvonne Greenstreet said will “ensure results relevant not only for health authorities but also for access and clinical practice in order to ultimately reach as many patients as possible.”

On a call with investors, execs underscored the massive need for better hypertension drugs: Over 200 million people are believed to be affected by primary hypertension, and despite widespread availability of therapies, said chief medical officer Pushkal Garg, “80% of hypertensive patients are not at their target blood pressure goal.”

To capture how much zilebesiran can add to existing standard of care, Garg announced during the call that Alnylam will be adding a new trial to the two existing Phase II trials it’s already running. While KARDIA-1 gives zilebesiran without additional antihypertensive medication and KARDIA-2 gives zilebesiran on top of one antihypertensive medication, the new study, KARDIA-3, will focus on patients with uncontrolled hypertension and high CV risk on at least two other antihypertensive therapies.

Pushkal Garg

“We see this as an important stepping stone to characterizing the blood pressure effects and safety in this intended target population and to helping us efficiently design and power the CVOT,” he said, referring to the Phase III cardiovascular outcomes trial.

KARDIA-1 and KARDIA-2 have topline results slated for mid-2023 and early 2024, respectively, while KARDIA-3 is expected to begin in 2024.

Cardiovascular “hasn’t been a big focus for Roche from a pipeline perspective in recent years,” Barclays analysts wrote, “but has been a renewed area of investment for large pharma peers” such as Bayer, Merck and Novartis.

Notably, Alnylam was the initial developer of Leqvio (inclisiran), a rising star in Novartis’ cardiovascular portfolio.

In a statement, Roche Pharma CEO Teresa Graham highlighted Roche’s “leadership in cardiovascular diagnostics” and “global commercial footprint.”

Alnylam steered zilebesiran into Phase II after showing in Phase I that the drug could lower levels of serum angiotensinogen (AGT), which is believed to play a role in regulating blood pressure. It’s designed to be dosed subcutaneously every six months.

Roche and Alnylam had teamed up back in 2007 for a research deal, long before Alnylam’s gene-silencing RNAi tech yielded its first approval, but dissolved the pact a few years later.

Editor’s note: This story has been updated to include comments from Alnylam’s investor call.

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