Alnylam‘s zilebesiran Fails to Achieve statistically Significant Blood Pressure Reduction in Phase 2 Trial
BARCELONA, SPAIN - Alnylam Pharmaceuticals’ investigational RNAi therapy, zilebesiran, did not demonstrate a statistically significant reduction in blood pressure during a mid-stage clinical trial, data presented Saturday at the European Society of Cardiology meeting revealed. While the treatment showed a reduction in systolic blood pressure compared to placebo, the results fell short of statistical significance.
The findings represent a setback for Alnylam, which is developing zilebesiran as a potential onc-monthly or twice-yearly treatment for hypertension, a condition affecting over 120 million U.S. adults and a leading cause of cardiovascular disease. Current hypertension treatments often require daily medication, and a longer-acting therapy could substantially improve patient adherence and outcomes. The trial’s outcome casts doubt on the drug’s potential to disrupt the standard of care.
Researchers evaluated two doses of zilebesiran – 300 mg and 600 mg – against a placebo in patients with hypertension. At three months, the 300 mg dose resulted in a 3.9 mmHG reduction in systolic blood pressure compared to placebo. This difference increased to 3.9 mmHG at six months. However, these reductions were not statistically significant, meaning the observed effects could be due to chance. Testing a higher 600 mg dose did not yield additional benefits.
Zilebesiran works by silencing the ANGPTL3 gene, which regulates blood pressure. Alnylam will need to carefully analyze the full dataset and determine next steps for the program, possibly including adjustments to the trial design or dosage. Further advancement will hinge on demonstrating a clear and statistically significant benefit in larger, late-stage trials.
