Long-Term Efficacy and Safety of ARRY-371797 (PF-07265803) in Patients With Lamin A/C–Related Dilated Cardiomyopathy
| Autor: | Daniel Philip Judge, Neal Kush Lakdawala, Matthew Roy Grayson Taylor, Luisa Mestroni, Huihua Li, Colleen Oliver, Franca Stedile Angeli, Patrice Anne Lee, Calum Archibald MacRae |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Adult
Cardiomyopathy Dilated Male Indazoles Middle Aged Ethylenediamines Lamin Type A Mitogen-Activated Protein Kinase 14 Clinical Trials Phase II as Topic Clinical Trials Phase III as Topic Natriuretic Peptide Brain Humans Female Cardiology and Cardiovascular Medicine Randomized Controlled Trials as Topic |
| Zdroj: | The American Journal of Cardiology. 183:93-98 |
| ISSN: | 0002-9149 |
| DOI: | 10.1016/j.amjcard.2022.08.001 |
| Popis: | 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 by30 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). |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect