Alnylam’s Zilebesiran Shows Positive Phase II Results in Reducing Blood Pressure

Pictured: Alnylam headquarters in Cambridge, Massa

Pictured: Alnylam headquarters in Cambridge, Massa

hapabapa/Getty Images

A mid-stage study of Alnylam Therapeutics’ experimental RNAi-based drug to treat hypertension met its primary endpoint.

Pictured: Alnylam headquarters in Cambridge, Massachusetts/iStock, hapabapa

Alnylam Therapeutics announced Tuesday that its investigational drug to treat hypertension, which is being co-developed with Roche, hit its primary endpoint in a Phase II study.

The company said that zilebesiran, an RNAi-based drug that goes after liver-expressed angiotensinogen (AGT) for treating hypertension, met its primary endpoint of a statistically significant reduction in 24-hour mean systolic blood pressure in the third month.

In the KARDIA-2 trial, zilebesiran was added to three standard hypertension therapies—indapamide, amlodipine, or olmesartan. While Alnylam did not disclose any specific data, the drug did show “encouraging” safety and tolerability when added to these antihypertensives.

Alnylam contends the results of Phase II study support further development. The company plans to present the full results at the American College of Cardiology Annual Scientific Session on April 7, 2024.

“We are thrilled that a single dose of zilebesiran achieved clinically significant, additional reductions in systolic blood pressure when administered to patients who are not adequately controlled with commonly prescribed antihypertensives,” Simon Fox, vice president and zilebesiran program lead at Alnylam, said in a statement. “These KARDIA-2 results, showing durable additional levels of blood pressure reduction on top of what is achieved by standard of care first-line antihypertensives with an encouraging safety profile, reinforce our confidence in zilebesiran’s differentiated profile.”

The study started in 2021 and is estimated to be completed in 2025. The global trial enrolled 672 patients with hypertension, according to Alnylam.

Roche and Alnylam have started a Phase II study investigating zilebesiran’s use as an add-on therapy in adults with high cardiovascular risk and uncontrolled hypertension despite treatment with two to four antihypertensive medications. The primary endpoint for this trial will be the change in the baseline at month three in the mean seated office systolic blood pressure (SBP).

Other endpoints include a change in the third month in the 24-hour mean SBP assessed by ambulatory blood pressure monitoring (ABPM) and a change at month six in the seated office SBP assessed by ABPM.

Alnylam is also looking to adapt another trial. Last month, the company announced it would adjust the primary and secondary endpoints for a Phase III trial of its RNA interface therapy Amvuttra (vutrisiran) in patients with ATTR amyloidosis and cardiomyopathy.

Tyler Patchen is a staff writer at BioSpace. You can reach him at Follow him on LinkedIn.

Tyler Patchen is a staff writer at BioSpace. You can reach him at Follow him on LinkedIn.