Slide 1: Advances in Niemann-Pick Disease Type C Treatment: The Role of Arimoclomol
Advances in Niemann- Pick Disease Type C Treatment: The Role of Arimoclomol Barbara K. Burton, MD Professor of Pediatrics Northwestern University Feinberg School of Medicine Attending Physician Division of Genetics, Genomics and Metabolism Ann & Robert H. Lurie Children's Hospital of Chicago MRC-250
Slide 2: Disclaimer
Disclaimer • Dr. Burton is a paid consultant for Zevra Therapeutics • This program is sponsored by Zevra Therapeutics and is not certified for continuing education credit • The information in this program is consistent with FDA-approved prescribing information • Intended for US audiences only
Slide 3: Niemann-Pick Disease Type C Is a Progressive Neurodegenerative Disease
Niemann-Pick Disease Type C Is a Progressive Neurodegenerative Disease Clinical course ranges from a more rapid, fatal neonatal or NPC is a infantile disorder while genetic, life- adult onset often limiting disorder1 manifests as a slowly progressing neurodegenerative disease4,5 NPC is an ultra-rare
Slide 4: Pathogenic Gene Variants Lead to Abnormal Lysosomal Function
Pathogenic Gene Variants Lead to Abnormal Lysosomal Function1 Over time, this leads to This accumulation of neurodegeneration as NPC is a lysosomal NPC pathogenic gene cholesterol in lysosomes well as peripheral organ storage disease with variants are associated leads to cell dysfunction dysfunction
Slide 5: MIPLYFFA arimoclomol capsules
MIPLYFFA® arimoclomol capsules
Slide 6: Pronunciation Guide
AAO SSSSAANN Pronunciation Guide MIPLYFFA Pronounced (mye-plye’-fah) SZEVRA THERAPEUTICS Arimoclomol Pronounced (air-im-OCK-lo-mall)
Slide 7: Arimoclomol Improves Lysosomal Function in NPC1
Arimoclomol Improves Lysosomal Function in NPC1 Endoplasmic reticulum 1 2 MIPLYFFA Arimoclomol Golgi 1 apparatus activates These genes then Transcription express more of the transcription factors, leading to factors 2 2 NPC1 protein as well NPC1 CLEAR upregulation of protein proteins as other protei
Slide 8: Measuring the Efficacy of Arimoclomol
Measuring the Efficacy of Arimoclomol Using a validated scale for the measurement of NPC disease progression 5-Domain NPCCSS Ambulation Swallowing • The NPC clinical severity scales (NPCCSS) Fine motor skills Speech specifically measure NPC disease progression1 Cognition • The scales were designed w
Slide 9: Studied in a Well-Controlled Clinical Trial
Studied in a Well-Controlled Clinical Trial Safety and effectiveness of arimoclomol was studied in a 12-month multicenter, randomized, double-blind, placebo-controlled trial in participants with NPC, aged 2–19 years1 *Stratified for miglustat use. †Observed values. Trial 1, 76% of patients in the MI
Slide 10: Proven Effectiveness in Halting Disease Progression in Patients who also Received Miglustat
Proven Effectiveness in Halting Disease Progression in Patients who also Received Miglustat1 NPC SYMPTOM REDUCTION AT 12 MONTHS 3.0 Arimoclomol, in combination 2.5 MIPLYFFA with miglustat with miglustat, halted baseline in R4DNPCCSS Placebo with miglustat 1.9 disease progression 2.0 Mean change from
Slide 11: First FDA-approved NPC Treatment with Long-Term Effectiveness of up to 5 Years
Arimoclomol is the First FDA-approved NPC Treatment that has Demonstrated Long-Term Effectiveness of up to 5 years1,2 Continued effectiveness in open-label extension (OLE) • Observed disease severity progressed slowly over the 48 months, with a stepwise progression pattern2 • Expected annual progres
Slide 12: 12-month Trial Adverse Events Generally Mild to Moderate
In the 12-month Trial Adverse Events Were Generally Mild to Moderate in Severity, and Few Led to a Withdrawal of Treatment MIPLYFFA Placebo with miglustat with miglustat Adverse Reaction n=26 n=13 n (%) n (%) Upper respiratory tract infection* 8 (31) 2 (15) Common adverse reactions Diarrhea 6 (23) 3
Slide 13: Arimoclomol Well-Tolerated with No New Safety Signals over 4 Years
Arimoclomol was Well-Tolerated with No New Safety Signals Observed over 4 Years1 The overall pattern of frequently reported AEs was stable over the 48 months and consistent with MIPLYFFA observations from the double-blind phase of the with miglustat trial. The 3 most common AEs were: N=41 n (%) • 38
Slide 14: Important Safety Information
Important Safety Information WHAT is MIPLYFFA [mye-plye’-fah]? MIPLYFFA is prescription medicine used in combination with a drug called miglustat to treat neurological symptoms of Niemann- Pick disease type C (NPC) in patients 2 years of age and older. IMPORTANT SAFETY INFORMATION Before starting MI
Slide 15: Important Safety Information (continued)
Important Safety Information (continued) The most common side effects of MIPLYFFA in patients also taking miglustat include upper respiratory tract infection, diarrhea and decreased weight. These are not all the possible side effects of MIPLYFFA. Call your HCP for medical advice about side effects.
Slide 16: Clinical Trial Summary
Clinical Trial Summary • Arimoclomol specifically addresses the underlying pathophysiology of NPC3 • MIPLYFFA, in combination with miglustat, is the only approved treatment for NPC with a 12-month placebo-controlled trial using a validated scale for NPC showing a clinically meaningful improvement in
Slide 17: Symptom Management for NPC
Symptom Management for NPC Specific Therapies Can Improve NPC-associated Symptoms Cataplexy and Dystonia and Spasticity Ataxia Psychiatric Illness Seizures Tremor • Muscle relaxants1 • Tricyclic anti- • Leucine • Anticholinergics2 • Antipsychotic • Anti-spasmodics1 depressants1,2 supplementation3 •
Slide 18: MIPLYFFA Has Convenient Dosing and Flexible Administration Options
MIPLYFFA Has Convenient Dosing and Flexible Administration Options Dosing is available in 4 different strengths and is based on body weight Administration† One capsule Recommended MIPLYFFA dose for patients aged or 2 years and older 18-33 lb >33-60 lb >60-121 lb >121 lb Body weight (8-15 kg) (>15-30
Slide 19: MIPLYFFA Is Ordered and Sent Directly to Patients Through the AmplifyAssist Program
MIPLYFFA Is Ordered and Sent Directly to Patients Through the AmplifyAssistTM Program AmplifyAssist is a support program for caregivers and patients living with NPC and taking MIPLYFFA Clinical support* Coverage support Prescription support To learn more about AmplifyAssist, please visit the Zevra t
Slide 20: Summary
Summary First FDA-approved NPC treatment Clinically meaningful difference Proven robust and enduring outcomes Scan the QR code for more Well-tolerated with no new safety signals information about MIPLYFFA Learn more at MIPLYFFA.com. Convenient dosing and flexible administration Support for patients
Slide 21: Thank You & Questions
SZEVRA THERAPEUTICS Thank You & Questions