Long-Term Efficacy and Safety of ARRY-371797 (PF-07265803) in Patients With Lamin A/C-Related Dilated Cardiomyopathy

Am J Cardiol. 2022 Nov 15:183:93-98. doi: 10.1016/j.amjcard.2022.08.001. Epub 2022 Sep 13.


Dilated cardiomyopathy associated with lamin A/C (LMNA) gene variants (LMNA-related dilated cardiomyopathy [DCM]) is a life-threatening condition with a high unmet need, accounting for approximately 6% of idiopathic DCM cases. Currently, no disease-specific treatments target the underlying disease mechanism. ARRY-371797 (PF-07265803), a potent, selective, oral, small-molecule inhibitor of the p38α mitogen-activated protein kinase pathway, improved 6-minute walk test (6MWT) distance in 12 patients with symptomatic LMNA-related DCM in a 48-week, open-label, phase 2 study. This long-term extension study examined the safety and efficacy of ARRY-371797 in patients from the phase 2 study. 6MWT, N-terminal pro-B-type natriuretic peptide concentration, and 12-item Kansas City Cardiomyopathy Questionnaire score were assessed at weeks 48, 72, 96, 120, and 144 from phase 2 study baseline. Eight patients enrolled (mean [SD] age, 51 [10] years, 4 male). Mean 6MWT increased by >30 m (>10%) from phase 2 study baseline up to week 120. The decrease in N-terminal pro-B-type natriuretic peptide observed in the phase 2 study was maintained throughout the present study. Twelve-item Kansas City Cardiomyopathy Questionnaire Physical Limitation increased from baseline at all visits except week 96 (range: -0.8 [week 96] to 13.8 [week 120]); results for other domains were variable. Treatment was generally well tolerated; 2 patients discontinued because of causes not considered treatment-related. There were no deaths. ARRY-371797 was generally well tolerated over median (range) 155.7 (61 to 327)-week exposure; evidence suggested preserved exercise capacity over the study period. The ongoing, pivotal, phase 3, randomized, placebo-controlled study REALM-DCM investigates the efficacy and safety of ARRY-371797 (PF-07265803) in LMNA-related DCM. (ClinicalTrials.gov Identifier: NCT02351856).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cardiomyopathy, Dilated* / drug therapy
  • Cardiomyopathy, Dilated* / genetics
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Ethylenediamines* / adverse effects
  • Female
  • Humans
  • Indazoles* / adverse effects
  • Lamin Type A / genetics
  • Lamin Type A / metabolism
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinase 14
  • Natriuretic Peptide, Brain
  • Randomized Controlled Trials as Topic


  • ARRY-371797
  • Ethylenediamines
  • Indazoles
  • Lamin Type A
  • Natriuretic Peptide, Brain
  • Mitogen-Activated Protein Kinase 14

Associated data

  • ClinicalTrials.gov/NCT02351856