Efficacy and Safety of ARRY-371797 in LMNA-Related Dilated Cardiomyopathy: A Phase 2 Study

Circ Genom Precis Med. 2023 Feb;16(1):e003730. doi: 10.1161/CIRCGEN.122.003730. Epub 2022 Dec 14.


Background: Lamin A/C gene (LMNA)-related dilated cardiomyopathy is a serious and life-threatening condition with a high unmet medical need. This phase 2 study assessed the effects of the oral selective p38 mitogen-activated protein kinase inhibitor ARRY-371797 on functional capacity and cardiac function in patients with LMNA-related dilated cardiomyopathy.

Methods: Patients with LMNA-related dilated cardiomyopathy in New York Heart Association class II-IIIA, on background heart failure treatment, received ARRY-371797 100 or 400 mg twice daily for 48 weeks. The primary end point was change from baseline in the 6-minute walk test distance at 12 weeks. Secondary end points included changes over time in 6-minute walk test distance, NT-proBNP (N-terminal pro-B-type natriuretic peptide) concentration, left ventricular ejection fraction, and quality-of-life scores on the Kansas City Cardiomyopathy Questionnaire. Data from the 2 dose groups were combined.

Results: Twelve patients were enrolled; median (minimum, maximum) 6-minute walk test distance at baseline was 314 (246, 412) m. At week 12, the mean (80% CI) increase from baseline in 6-minute walk test distance was 69 (39, 100) m (median, 47 m). Median NT-proBNP concentration declined from 1409 pg/mL at baseline to 848 pg/mL at week 12. Mean left ventricular ejection fraction was stable at week 12. There was a trend toward improvement in Kansas City Cardiomyopathy Questionnaire Overall and Clinical Summary scores at week 12. No clinically significant drug-related safety concerns were identified.

Conclusions: ARRY-371797 was well tolerated and resulted in potential increases in functional capacity and lower concentrations of cardiac biomarker NT-proBNP in patients with LMNA-related dilated cardiomyopathy.

Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT02057341.

Keywords: LMNA-related dilated cardiomyopathy; clinical trial; lamin A/C; p38 MAPK.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiomyopathy, Dilated* / drug therapy
  • Cardiomyopathy, Dilated* / genetics
  • Humans
  • Indazoles / pharmacology
  • Indazoles / therapeutic use
  • Lamin Type A / genetics
  • Stroke Volume
  • Ventricular Function, Left


  • ARRY-371797
  • Indazoles
  • LMNA protein, human
  • Lamin Type A

Associated data

  • ClinicalTrials.gov/NCT02057341