Zilebesiran Phase 2 Results Show Long-Lasting Blood Pressure Impact

Zilebesiran’s path towards becoming the first long-lasting antihypertensive medication gained more momentum, with new topline Phase 2 results demonstrating that a single injection significantly reduces systolic blood pressure through six months.

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

  • Perhaps more notably, zilebesiran’s ability to control blood pressure over long periods could address the daily medication adherence challenges that often undermine hypertension care.

Zilebesiran is wrapping up an epic summer, starting with a Phase 1 trial showing that one injection can control blood pressure for up to six months, which was quickly followed by a co-development and co-commercialization alliance with Roche that’s worth up to $2.8B, and culminating with these new Phase 2 results from its KARDIA-1 trial.

The KARDIA-1 trial randomized 394 adults with untreated hypertension or taking one or more anti-hypertensive medications into one of five treatment arms, and followed them over 12-month and extended double-blind periods. 

  • 150 mg zilebesiran every six months
  • 300 mg zilebesiran every six months
  • 300 mg zilebesiran every three months
  • 600 mg zilebesiran every six months
  • Placebo, followed by zilebesiran after six months

The 300 mg and 600 mg zilebesiran groups achieved the study’s primary endpoint, with at least 15 mmHg lower 24-hour systolic blood pressure levels than placebo patients (p<0.0001).

All zilebesiran groups also met key secondary endpoints, including significant changes in mean 24-hour SBP at six months and in office SBP at three and six months.

Like the Phase 1 trial, the KARDIA-1 trial’s zilebesiran group had a lower rate of serious adverse events than the placebo patients (3.6% vs. 6.7%), and no serious events were believed to be related to the drug.

Alnylam highlighted these Phase 2 results as more evidence of zilebesiran’s safety and sustained efficacy, supporting the drug’s continued research and development.

The Takeaway

Although zilebesiran has a lot more to prove, its initial Phase 1 and 2 results (along with its big support from Roche) show that it’s making solid progress towards becoming the first long-lasting antihypertensive medication. Given the challenges with bringing many patients’ hypertension under control, that could be a big deal.

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