Slide 1: Efficacy results from a 12-month double-blind randomized trial of arimoclomol for NPC
Efficacy results from a 12-month double-blind randomized trial of arimoclomol for the treatment of Niemann-Pick disease type C – Presenting a rescored 4-domain NPC Clinical Severity Scale Dr. Eugen Mengel, MD SphinCS, Clinical Science for LSD Hochheim, Germany
Slide 2: Introduction
Introduction • Niemann-Pick disease type C (NPC) is an ultra-rare, progressive neurodegenerative lysosomal disease • Clinical presentation is heterogeneous with declining neurological functions • A validated 5-domain version of NPCCSS (5DNPCCSS)1 including the Swallow, Fine Motor Skills, Speech, Amb
Slide 3: From the Clinician-Reported 5DNPCCSS to R4DNPCCSS
From the Clinician-Reported 5DNPCCSS to R4DNPCCSS 5-Domain NPCCSS1 R4-Domain Ambulation NPCCSS Ambulation Fine Motor Skills Fine Motor Skills Speech Speech Swallow Rescored Swallow Cognition Individual domain score: 0-5 Individual domain score: 0-5 Maximum score: 25 Maximum score: 20 1. Evans W, Pat
Slide 4: Methods: Update of the scoring methodology for the swallow domain
Methods: Update of the scoring methodology for the swallow domain • Swallow domain validated by performance tests1: • Modified PAS score (NIH-adapted Penetration Aspiration Scale) • ASHA-NOMS (American Speech-Language-Hearing Association National Outcome Measure) • Original scoring methodology for t
Slide 5: Original swallow domain scoring could yield inaccurate equivalencies in disease severity
Original swallow domain scoring could yield inaccurate equivalencies in disease severity Original Swallow Score Patient A Patient B Normal, no dysphagia 0 Cough while eating 1 1 Intermittent dysphagia with liquids +1 Intermittent dysphagia with solids +1 Dysphagia with liquids +2 +2 Dysphagia with s
Slide 6: Rescored swallow domain
Rescored swallow domain Updated Swallow Score Normal, no dysphagia 0 Scores clearly Cough while eating 1 delineated ▪ Each step-wise Intermittent dysphagia 2 increase in swallow Dysphagia 3 dysfunction matched with Nasogastric tube or gastric tube for supplemental feeding 4 numeric point increase in
Slide 7: R4DNPCCSS is a reliable and validated tool
R4DNPCCSS is a reliable and validated tool1 Polychoric and NPCCSS Domain Performance Spearman Correlation (score range) at 0, 6 and 12 months Ambulation SARA GAIT (0-8) 0.85-0.97 (0-5, a score of 3 is not an option) SARA Finger chase (0-4) SARA Nose-finger test (0-4) 0.58-0.93 Fine motor skills (0-5
Slide 8: NPC-002 Trial
NPC-002 Trial 12-Month 4-year Results:1 Double-Blind Phase Open-Label Extension (OLE) • Prespecified primary endpoint: • Statistically significant change Arimoclomol + from baseline in 5DNPCCSS at Routine Clinical Care Month 12 using MMRM model Enrollment N = 34 Arimoclomol + 2:1* N = 50 RoutineisCl
Slide 9: Treatment difference at 12 months
Treatment difference at 12 months Favors Favors Difference p-value arimoclomol placebo (95% CI) 5DNPCCSS (Prespecified)1 -1.40 0.0456 MMRM (-2.76, -0.03) R4DNPCCSS -1.70 0.0155 MMRM (-3.05, -0.34) R4DNPCCSS miglustat subgroup -2.2 0.0077 ANCOVA (-3.8, -0.6) -5 -4 -3 -2 -1 0 1 2 3 4 5 Mean Difference
Slide 10: Change in R4DNPCCSS over months in patients who also received miglustat
Change in R4DNPCCSS over 12 months in patients who also received miglustat 3.0 R4DNPCCSS Patients on at 12 months miglustat 2.5 Mean change (95% CI) -2.2 (-3.8, -0.6) p-value 0.0077 Mean change from baseline 2.0 1.9 in R4DNPCCSS (SE) 1.7 1.5 1.3 1.0 -2.2 0.5 0.4 0.0 -0.1 -0.2 -0.5 -0.3 -0.3 -1.0 Ari
Slide 11: Safety
Safety Arimoclomol Placebo Preferred terms reported in > 10% patients, n (%) N = 34 N = 16 Any AE 30 (88%) 12 (75%) Vomiting 8 (24%) 4 (25%) Diarrhea 7 (21%) 3 (19%) Constipation 7 (21%) 3 (19%) Pyrexia 6 (18%) 3 (19%) Upper respiratory tract infection 6 (18%) 1 (6%) Rhinitis 5 (15%) 2 (13%) Weight
Slide 12: Conclusions
Conclusions Prespecified Miglustat Subgroup • R4DNPCCSS is a valid and reliable endpoint • Consistent outcomes with the 5DNPCCSS were demonstrated • Arimoclomol in combination with miglustat slowed disease progression through 12 months
Slide 13: Thank you to NPC patients and their families!
Thank you to NPC patients and their families! Further Information: Co-authors: • Poster 228 “Efficacy Results From a 12-month Double-blind Randomized Trial of Arimoclomol for the Treatment of Niemann-Pick Disease Type C - • Marc Patterson Presenting a Rescored 4-Domain NPC Clinical Severity Scale” N