Benzinga | Nov 8, 2021 07:11AM EST

Alnylam Pharmaceuticals Initiates KARDIA-2 Phase 2 Study Of Investigational Zilebesiran (ALN-AGT) In Patients With Inadequately Controlled Hypertension

Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY), the leading RNAi therapeutics company, today announced initiation of KARDIA-2, a global Phase 2 study to evaluate the efficacy and safety of zilebesiran (formerly known as ALN-AGT), an investigational subcutaneous RNAi therapeutic targeting liver-expressed angiotensinogen (AGT) in development for the treatment of hypertension. KARDIA-2 will evaluate the efficacy and safety of zilebesiran administered biannually as a concomitant therapy in patients whose blood pressure is not adequately controlled by standard of care antihypertensive medications.

The primary endpoint of KARDIA-2 is the change from baseline in 24-hour mean systolic blood pressure (SBP) after three months of treatment, as measured by ambulatory blood pressure monitoring (ABPM). Additional endpoints will include change from baseline in blood pressure at six months and time-averaged reduction of blood pressure as a measure of tonic control. Safety will be assessed throughout the study. KARDIA-2 has been activated at clinical sites in the U.S. and will be conducted at approximately 80 clinical study centers worldwide.

"Hypertension remains one of the top preventable causes of death around the world. Despite the availability of efficacious interventions, most patients on antihypertensive medications fail to achieve guideline-recommended goals for blood pressure control, increasing their risk for cardiovascular events, primarily stroke and heart attack. A lack of patient adherence to therapy with daily oral medications contributes to the challenges of achieving tonic blood pressure control," said Weinong Guo, M.D., Ph.D., Senior Vice President of Clinical Development at Alnylam. "With the global prevalence of hypertension expected to increase by up to 20 percent by 2025, the initiation of KARDIA-2 represents Alnylam's commitment to advance zilebesiran as an innovative potential treatment with an infrequent dosing regimen that could one day help address this global public health crisis."

KARDIA-2 is the second Phase 2 study evaluating zilebesiran in hypertension, with KARDIA-1, announced earlier this year, assessing zilebesiran as monotherapy across different doses administered quarterly and biannually. These Phase 2 studies are based on encouraging Phase 1 data, including results presented earlier this year at the 2021 Joint Meeting of the European Society of Hypertension (ESH) and the International Society of Hypertension (ISH). Additional clinical results from the Phase 1 study of zilebesiran will be presented at the American Heart Association (AHA) Scientific Sessions 2021, being held November 13-15, 2021.