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Biannual zilebesiran associated with substantial BP reductions

Presented by
Prof. George Bakris, University of Chicago, USA
AHA 2023
Phase 2, KARDIA-1
In the phase 2 KARDIA-1 study, a single subcutaneous dose of zilebesiran demonstrated encouraging reductions in systolic blood pressure (BP) in hypertensive patients at 3 and 6 months of follow-up compared with placebo. The investigational agent zilebesiran is further assessed as add-on therapy for patients with hypertension in the phase 2 KARDIA-2 trial.

The phase 2 KARDIA-1 study (NCT04936035) randomised 394 participants with mild-to-moderate hypertension 1:1:1:1:1 to placebo or 1 of 4 dose-levels of the subcutaneously administered RNA-interference therapeutic zilebesiran, ranging from 150 mg, once every 6 months, to 600 mg, once every 6 months. The primary endpoint was the change in 24-hour mean ambulatory systolic BP from baseline to 3 months. Prof. George Bakris (University of Chicago, IL, USA) presented the findings.

“At 3 months, all zilebesiran groups were associated with significantly larger reductions in 24-hour mean ambulatory systolic BP than placebo,” said Prof. Bakris. In the lowest-dose group, the reduction was -14.1 mmHg compared with placebo (P<0.0001), and in the highest-dose group, the reduction was -15.7 mmHg compared with placebo (P<0.0001).

These reductions appeared to be maintained at 6 months, with corresponding reductions of -11.1 mmHg for the lowest-dose group and -14.2 for the highest-dose group. “The agent also displayed a favourable safety profile,” according to Prof. Bakris. No serious or severe drug-related adverse events were reported. However, the rates of hyperkalaemia and hypotension were somewhat higher in the zilebesiran groups (6% vs 3%; 4% vs 1%). According to Prof. Bakris, these cases were mostly mild or moderate and did not lead to treatment discontinuations.

These data support the quarterly or biannual dosing of subcutaneous zilebesiran to reduce the BP of patients with hypertension.

    1. Bakris G, et al. Sustained blood pressure reduction with the RNA interference therapeutic zilebesiran: primary results from Kardia-1, a phase 2 study in patients with hypertension. LB04, AHA Scientific Sessions 2023, 10–12 November, Philadelphia, USA.


Medical writing support was provided by Robert van den Heuvel.
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