Alnylam, Roche blood pressure drug scores in second mid-stage trial

Dive Brief:

• An experimental RNA-based medicine developed by Alnylam Pharmaceuticals, when added to standard drugs, helped lower blood pressure significantly more than a placebo in a Phase 2 trial of people with uncontrolled hypertension, the company said Tuesday.

• The drug, zilebesiran, succeeded in an earlier mid-stage trial last year evaluating multiple doses of the therapy. The results disclosed Tuesday were from a study testing Alnylam’s drug alongside one of three standard blood pressure medicines, a trial some analysts have described as a better barometer of zilebesiran’s commercial potential.

• Roche last year paid Alnylam $310 million to split rights to the therapy. The partners have just started a third Phase 2 trial in people with uncontrolled hypertension and are currently receiving two to four other therapies. Data could come next year, the companies said Tuesday.

Dive Insight:

Alnylam is best known for its rare disease work, having brought four such medicines to market since 2018. But it has also dabbled in cardiology research, first with a cholesterol-lowering medicine that Novartis now sells, Leqvio, and now zilebesiran.

Developing cardiology medicines is an expensive and time-consuming endeavor, involving large and lengthy trials that prove whether drugs can definitively reduce the risk of heart problems and death. Rather than foot the bill for those studies and build the associated commercial infrastructure, Alnylam has looked to partnerships instead.

In 2013, for instance, the company licensed the drug that would become Leqvio to The Medicines Co. A decade later, it turned to Roche to help advance zilebesiran.

Zilebesiran is designed to suppress the production of a protein called angiotensinogen that’s involved in the regulation of blood pressure. Alnylam is developing it for forms of blood pressure that remain stubbornly high despite treatment with standard medications.

The trial Alnylam and Roche reported today was called KARDIA-2, which tested zilebesiran or a placebo as an add-on to three different types of marketed hypertension drugs.

The companies didn’t release detailed findings, leaving out important information about the magnitude of the drug’s effects. They only said a single dose of zilebesiran plus each of the standard drugs resulted in statistically significant reductions in blood pressure at three months when compared to those therapies and a placebo.

Study results will be presented at the American College of Cardiology meeting on April 7.

In a note to clients on Tuesday, William Blair analyst Myles Minter wrote that cardiologists and regulators will likely want to see a blood pressure reduction of five points or more, a figure that equates to a 10% reduction in the lifetime relative risk of a cardiovascular event.

The new study announced Tuesday, meanwhile, is set to enroll 390 people with uncontrolled hypertension and either a history of heart disease or at high risk of it. Study participants will receive a single dose of zilebesiran and have their blood pressure checked after three months.

Success in that study could pave the way for a definitive “outcomes” trial. Roche will pay 60% of the costs of that trial under the partnership signed last year.

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