Zevra Announces Publication of MIPLYFFA® Mechanism of Action Manuscript in Molecular Genetics and Metabolism

Core Insights - Zevra Therapeutics, Inc. has published significant findings regarding the mechanism of action of its therapy MIPLYFFA (arimoclomol) for Niemann-Pick disease type C (NPC), highlighting its potential to address the underlying pathology of the disease [1][2][3] Group 1: Mechanism of Action - The publication details how arimoclomol enhances the translocation of translation factors EB and E3 (TFEB & TFE3) from the cytosol to the nucleus, initiating a cascade that upregulates coordinated lysosomal expression and regulation (CLEAR) genes, including NPC1 [2] - Increased expression of CLEAR genes leads to higher NPC1 protein levels in lysosomes, improving cholesterol trafficking and correlating with better neurological behaviors in animal models [2] Group 2: Clinical Significance - MIPLYFFA, approved by the U.S. FDA on September 20, 2024, is indicated for use in combination with miglustat for treating neurological manifestations of NPC in patients aged 2 years and older [3][4] - In a pivotal phase 3 trial, MIPLYFFA demonstrated the ability to halt disease progression compared to placebo, as measured by the NPC Clinical Severity Scale [3] Group 3: Safety Information - Common adverse reactions reported in clinical trials include upper respiratory tract infection, diarrhea, and decreased weight, with hypersensitivity reactions such as urticaria and angioedema noted in some patients [5][8][9] - MIPLYFFA may cause increased serum creatinine levels without affecting glomerular function, primarily occurring within the first month of treatment [7] Group 4: Company Overview - Zevra Therapeutics focuses on developing therapies for rare diseases, aiming to create transformational treatments for conditions with limited or no options [13] - The company employs data-driven strategies to navigate complex drug development challenges, striving to make new therapies accessible to the rare disease community [13]