Alnylam has started a phase 2 clinical trial of quarterly and biannual subcutaneous doses of potential hypertension drug zilebesiran. The proposed subcutaneous dosing is enabled by Alnylam’s Enhanced Stabilization Chemistry Plus (ESC+) GalNAc-conjugate delivery platform.
RNAi pioneer Alnylam has advanced its delivery capabilities throughout its history, culminating in the creation of its third-generation GalNAc conjugate ESC+. The latest iteration of the delivery platform is designed to improve the specificity and therapeutic index of Alnylam’s candidates while mitigating seed-mediated off-target effects.
Zilebesiran, formerly known as ALN-AGT, is one of a clutch of assets that will show whether the early promise of the platform holds up in the clinic. Alnylam shared phase 1 data earlier this year, setting it up to start a phase 2 study.
The study will randomize adults with mild to moderate hypertension to receive placebo or one of four zilebesiran dose regimens. Three of the treatment arms will test the effect of giving 150 mg to 600 mg of zilebesiran every six months. The fourth arm will evaluate 300 mg of zilebesiran given at three-month intervals. All the doses will be given subcutaneously.
Alnylam has picked change in systolic blood pressure from baseline to three months as the primary endpoint, with secondary objectives tracking changes out to six months. If the regimens work, they could make it easier for patients to control their blood pressure.
“Despite the availability of numerous anti-hypertensive medications, tonic control of blood pressure remains elusive and represents a major unmet need, elevating the risk of fatal and nonfatal cardiovascular events, primarily stroke and heart attack. In addition, lack of patient adherence to therapy with daily oral medications further contributes to the challenges of inadequate blood pressure control,” Weinong Guo, senior vice president of clinical development at Alnylam, said in a statement.
Alnylam plans to start a second phase 2 study later in the year.