RNAi therapeutics company Alnylam Pharmaceuticals (Nasdaq: ALNY) has announced positive topline results from a Phase 2 study of zilebesiran, an investigational RNA interference (RNAi) therapeutic designed to treat hypertension in patients at high cardiovascular risk.
The study achieved its primary endpoint, with zilebesiran demonstrating a significant reduction in systolic blood pressure at three months compared to a placebo. Both the 300 mg and 600 mg doses showed a placebo-subtracted reduction greater than 15 mmHg, indicating a dose-dependent effect. The study also met key secondary endpoints, including consistent and sustained reductions in SBP at six months.
The results are good news for pharma giant Roche, which entered into a $310 million strategic agreement with Alnylam in July this year to develop and commercialize zilebesiran.
Hypertension is a chronic condition characterized by elevated blood pressure levels, which can lead to serious health complications. Despite the availability of anti-hypertensive medications, there is a significant unmet medical need, especially in populations with poor medication adherence and high cardiovascular risk.
RNAi therapeutics leverage a cellular process that silences genes, blocking the production of disease-causing proteins at the genetic level, offering a new approach to treating genetic and other diseases. Zilebesiran is an investigational RNAi therapeutic designed to target angiotensinogen (AGT) and treat hypertension in high-risk populations. By inhibiting the synthesis of AGT in the liver, it aims to reduce AGT protein levels, potentially leading to sustained blood pressure reduction.
“We are thrilled that the KARDIA-1 Phase 2 results show zilebesiran’s ability to achieve sustained blood pressure reductions of greater than 15 mmHg, as well as long-term efficacy out to six months with infrequent dosing,” said Dr Simon Fox, Zilebesiran Program Lead at Alnylam. “We believe these results further validate the differentiated profile we observed in Phase 1. Moreover, they reinforce the potential for zilebesiran to be a transformative therapy to reduce cardiovascular risk in patients with hypertension and to offer new possibilities in a field of medicine that has seen limited innovation in nearly 20 years.”
The results suggest that zilebesiran could be a promising treatment for hypertension, particularly in patients with high cardiovascular risk who often face challenges with medication adherence. The findings from the trial will guide the determination of the optimal dose and dosing regimen for zilebesiran in future studies.
The study results will be presented at an upcoming scientific conference. Furthermore, Alnylam is conducting a second Phase 2 study, which evaluates zilebesiran in combination with standard anti-hypertensive medications, with results expected in early 2024.
