FDA Approves Aprocitentan for Treatment-Resistant HTN: Daily Dose

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Last week, we reported on the US Food and Drug Administration (FDA) approval of aprocitentan (Tryvio) as concomitant treatment for hypertension in adults whose blood pressure (BP) is not adequately controlled by other medications.

The approval

Aprocitentan is an endothelin receptor antagonist that inhibits binding of endothelin (ET)-1 to ETA and ETB receptors. The effects of ET-1 in the body are similar to the pathophysiology of hypertension, including its role in aldosterone production. Aprocitentan is the first systemic antihypertensive agent to target the ET pathway.

The FDA approval was based on the phase 3a multinational, blinded, randomized, parallel-group PRECISION trial that evaluated aprocitentan in adults with a seated systolic BP (SBP) of 140 mg HH or higher despite treatment with standard of care background therapy comprised of at least 3 antihypertensive drugs, including a diuretic.

Results showed a least square mean (LSM) change in office SBP of –15.3 mm Hg for aprocitentan 12.5 mg, –15.2 mmHg for aprocitentan 25 mg, and –11.5 mm Hg for placebo. Differences vs placebo translated to –3.8 mm Hg (97.5% CI, –6.8 to –0.8; P = .004) and –3.7 mm Hg (–6.7 to –0.8; P =. 005), respectively.

Analysis of differences for 24-hour ambulatory systolic blood pressure found changes from baseline of –4.2 mmHg (95% CI –6.2 to –2.1) and –5.9 mmHg (–7.9 to –3.8) with aprocitentan 12.5 mg and 25 mg, respectively. Findings from analysis of part 3 demonstrated a significant increase in office SBP for placebo vs aprocitentan (5.8 mm Hg, 95% CI 3.7 to 7.9; P < .001) after the 4 weeks of withdrawal.

The most frequent adverse event reported in the safety analyses of the trial was mild-to-moderate edema or fluid retention, observed among 9%, 18%, and 2% of participants receiving aprocitentan 12.5 mg, 25 mg, and placebo, respectively, during part 1 of the trial. Fluid retention was cited as contributing to study discontinuation by 7 participants receiving the study drug.

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