Home > Pulmonology > ATS 2022 > Highlighted Advances > PAGANINI phase 2b data promising for eliapixant

PAGANINI phase 2b data promising for eliapixant

Presented by
Prof. Peter Dicpinigaitis, Albert Einstein College of Medicine, NY, USA
Conference
ATS 2022
Trial
Phase 2, PAGANINI
Doi
https://doi.org/10.55788/d266a780
The 12-week dose-ranging results of the phase 2b PAGANINI trial indicated efficacy of the selective P2X3 antagonist eliapixant in patients with refractory chronic cough, although a single liver safety signal warrants intensified monitoring going forward.

Prof. Peter Dicpinigaitis (Albert Einstein College of Medicine, NY, USA) presented the efficacy and safety data of eliapixant on chronic cough [1]. He explained that P2X3 receptors regulate afferent sensory nerve fibre ATP-mediated signalling, which in turn is thought to play an important role in sensory neural dysregulation associated with chronic cough. Eliapixant is a selective P2X3 receptor antagonist with greater potency and selectivity for the human P2X3 homotrimer than the P2X2/3 heterotrimer receptor [2].

To test the effect of eliapixant on chronic cough, the randomised, phase 2b PAGANINI (NCT04562155) enrolled 310 patients with refractory chronic cough lasting ≥12 months. Participants were randomised to 12 weeks of treatment with twice-daily placebo (n=77), or eliapixant 25 mg (n=75), 75 mg (n=78), or 150 mg (n=80). Baseline characteristics were reasonably well-balanced among the groups. The primary endpoint was the change from baseline in 24-hour cough frequency.

The results showed that a significant dose-response signal was established, with one-sided P-values of ≤0.1. From baseline to week 12, 24-hour cough count decreased with eliapixant for twice-daily doses of 25 mg, 75 mg, or 150 mg, respectively: -44%, -54%, -49%, compared with -34% for placebo. Awake cough count also decreased: -44%, -54%, and -53%, respectively, compared with -33% for placebo.

Mild adverse events were reported for both the placebo as well as eliapixant arms, and 1 serious hepatic adverse event of drug-induced liver injury did occur in a single individual in the 150 mg eliapixant arm, which spontaneously resolved upon discontinuation. Some taste- and smell-related adverse events were reported in 24% of participants in the eliapixant highest dose arm, although that decreased to background at 25 mg.

Prof. Dicpinigaitis concluded that eliapixant: (1) reduced 24-hour cough count versus placebo, with a safety and tolerability profile similar to other studies of eliapixant; (2) warrants intensified liver monitoring due to the single case of drug-induced liver injury; and (3) was associated with fewer taste-related adverse events in PAGANINI than reported in other trials with non-selective P2X3 antagonists.

  1. Dicpinigaitis P et al. Eliapixant in refractory chronic cough: the 12-week randomized, double-blind, placebo-controlled phase 2 PAGANINI trial. Session C93, ATS International Conference 2022, San Francisco, CA, USA, 13–18 May.
  2. Davenport AJ, et al. Sci Rep. 2021;11(1):19877.

 

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