Zevra Therapeutics has published long-term efficacy and safety data for MIPLYFFA (arimoclomol) in the peer-reviewed journal Molecular Genetics and Metabolism, demonstrating sustained disease progression reduction in Niemann-Pick disease type C (NPC) patients for at least five years. The study, titled "Long-term Efficacy and Safety of Arimoclomol in Niemann-Pick Disease Type C: Final Results of the Phase 2/3 NPC-002 48-month Open-label Extension Trial," represents a significant milestone for patients with this debilitating neurodegenerative disease.
Extended Treatment Benefits
The 48-month open-label extension (OLE) phase followed the completion of a 12-month pivotal, placebo-controlled, double-blind Phase 2/3 trial. The extension study included more than 270 patients worldwide, with some patients receiving treatment for as long as seven years. Efficacy was measured using the 5- and rescored 4-domain NPC Clinical Severity Scale, the only validated measurement tool for NPC progression.
"With MIPLYFFA, we have demonstrated its ability to halt disease progression through twelve months in our pivotal, double-blind, randomized, placebo-controlled study," said Adrian Quartel, M.D., FFPM, Zevra's Chief Medical Officer. "For those patients who are continuing to receive treatment through the open-label extension study, we have also shown that MIPLYFFA's clinically-meaningful impact on disease progression is sustained over multiple years."
Safety Profile Maintained
The long-term data showed no new safety concerns during the extended treatment period. The most common adverse reactions in the original trial (≥15%) in MIPLYFFA-treated patients who also received miglustat were upper respiratory tract infection, diarrhea, and decreased weight. Three patients (6%) discontinued treatment due to adverse reactions: one due to increased serum creatinine and two due to progressive urticaria and angioedema.
Mechanism of Action and Approval Status
MIPLYFFA works by increasing the activation of transcription factors EB (TFEB) and E3 (TFE3), resulting in the upregulation of coordinated lysosomal expression and regulation (CLEAR) genes. The drug has also been shown to reduce unesterified cholesterol in the lysosomes of human NPC fibroblasts, though the clinical significance of these findings is not fully understood.
The FDA approved MIPLYFFA on September 20, 2024, for use in combination with miglustat for treating neurological manifestations of NPC in adult and pediatric patients 2 years of age and older. The drug has also received Orphan Medicinal Product designation from the European Medicines Agency (EMA).
Clinical Considerations
Healthcare providers should monitor patients for hypersensitivity reactions, as urticaria and angioedema have been reported within the first two months of treatment. The drug may cause mean increases in serum creatinine of 10% to 20% compared to baseline, primarily occurring in the first month of treatment without affecting glomerular function. These increases reverse upon discontinuation.
MIPLYFFA is available in oral capsule strengths of 47 mg, 62 mg, 93 mg, and 124 mg, with dosage adjustments recommended for patients with renal impairment.
