Cardiology Pharmaceuticals

Zilebesiran’s Long-Lasting Antihypertensive Potential


Could the first long-lasting antihypertensive medication be on the way? Results of a Phase 1 study in NEJM suggests that Alnylam Pharmaceuticals’ zilebesiran is a frontrunner to become that drug, showing that a single injection controls blood pressure for up to six months.

Zilebesiran is an investigational RNA interference therapeutic agent that inhibits hepatic angiotensinogen synthesis, which plays a key role in the development of hypertension. 

  • That’s how zilebesiran works, but most news headlines and social media comments focused on how long it works, noting the BP control challenges created by poor adherence to daily antihypertensive pill regimens.

The Phase 1 study included 107 adults with hypertension and was performed in three parts, evaluating zilebesiran at different doses, with specific salt intake diets, and when combined with other hypertensives.

  • Zilebesiran use was associated with dose-dependent serum angiotensinogen level reductions that sustained over six months
  • A ≥200 mg dose of zilebesiran reduced systolic (>10 mm Hg) and diastolic (>5 mm Hg) blood pressure by week 8, which was consistent during day and night, and sustained over six months
  • A 800 mg dose of zilebesiran drove the greatest average systolic and diastolic BP reductions (22.5 mm HG & 10.8 mm HG) at month 6
  • Zilebesiran’s BP reductions were diminished among participants with high salt diets
  • BP reductions were greater when zilebesiran was combined with the BP drug irbesartan 

Adverse events were less common in the zilebesiran group than placebo (72% vs. 88%), most of which were mild or moderate, and there were no reports of hypotension, hyperkalemia, or worsening of renal function.

Although the study was short and small, and some aspects of zilebesiran’s efficacy and safety aren’t confirmed, the authors found these antihypertensive results to be strong enough to justify further research. 

Zilebesiran’s impact might also go beyond BP control, as the associated NEJM editorial suggested that it could also be able to treat other conditions related to renin-angiotensin activation such as kidney and heart disease.

The Takeaway

Although zilebesiran has a lot more to prove, these initial results are promising. And the adherence benefits of a long-lasting antihypertensive drug seems even more promising, once one is developed and approved.

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