Slide 1: Cerliponase alfa for CLN2 disease in an expanded patient cohort: interim results
Cerliponase alfa for the treatment of CLN2 disease in an expanded patient cohort including children younger than three years: Interim results from an ongoing clinical study Angela Schulz, MD, PhD University Medical Center Hamburg-Eppendorf, Germany
Slide 2: Disclosure Information
Disclosure Information Angela Schulz, MD, PhD • I have the following financial relationships to disclose: – Consultant: BioMarin Pharmaceutical Inc. – Grant/Research support: BioMarin Pharmaceutical Inc.
Slide 3: CLN2 Disease: A Form of Batten Disease
CLN2 Disease: A Form of Batten Disease • CLN2 disease is an autosomal recessive form of neuronal ceroid lipofuscinosis (NCL) – most common group of neurodegenerative disorders in children and adolescents – share a core set of symptoms: seizures, progressive cognitive and motor deterioration, blindne
Slide 4: Cerliponase Alfa: Approved Therapy for CLN2 Disease
Cerliponase Alfa: Approved Therapy for CLN2 Disease • Cerliponase alfa is a recombinant human form of TPP1 enzyme (rhTPP1)1 approved for treatment in the US and EU in 2017, and subsequently in a number of other countries worldwide CATHETER – Administered through an implanted Rickham or Ommaya device
Slide 5: The CLN2 Clinical Rating Scale: Four Functional Domains
The CLN2 Clinical Rating Scale: Four Functional Domains 3 Walk normally 2 Frequent falls, ataxia, independently walk >10 steps Motor 1 No unaided gait 0 Immobile, mostly bedridden • Motor and language loss central to 3 Normal disease morbidity and is primary 2 Loss of words, intelligible but abnorma
Slide 6: Natural History of CLN2 Disease: Decline in Motor-Language Score
Natural History of CLN2 Disease: Decline in Motor-Language Score ~2 points/year Clinical Score MOTOR and LANGUAGE Assessments Score Normal 3 Abnormal 2 Poor 1 No function 0 Sum of Motor & Language = Max Score of 6
Slide 7: Study Objectives and Design
Study Objectives and Design Study 190-203 Design • Open-label, multicenter, international trial of cerliponase alfa for approximately 3 years (144 weeks) • Dose age-adjusted for children <2 years Primary study objectives Key Inclusion criteria • Evaluate safety and tolerability of cerliponase alfa •
Slide 8: Study Objectives and Design: Efficacy Evaluation
Study Objectives and Design Efficacy Evaluation Primary efficacy endpoint is the rate of decline in score on motor and language domains of the CLN2 clinical rating scale Treated subjects were matched to historical natural history controls (DEM-CHILD NCL database) on the basis of: • Age at baseline:
Slide 9: Subject Demographics, Baseline Characteristics and Disposition
Subject Demographics, Baseline Characteristics and Disposition 190-203 Disposition, n (%) Enrolled 14 (100.0%) as of current data cutoff (26 April 2020) Treated 14 (100.0%) Completed study 10 (71.4%) Continuing on treatment 3 (21.4%) Discontinued from study 1 (7.1%) Age at enrollment, years mean (SD
Slide 10: Subject Drug Exposure Summary
Subject Drug Exposure Summary As of current data cutoff (26 April 2020) 190-203 (N=14) Study drug exposure, weeks mean (SD) 127.0 (26.94) median 141.9 range 64.4, 142.6 Total number of infusions mean (SD) 64.1 (13.86) median 72.0 range 31, 72
Slide 11: Rate of Decline in Motor-Language Score
Rate of Decline in Motor-Language Score Rate of Decline in ML Score Natural History 190-203 Difference (points per 48 weeks) (N=29) (N=12) Mean (SD) 1.24 (1.022) 0.14 (0.262) 1.10 SE (0.204) Median (IQR) 1.18 (0.45, 1.77) 0.00 (0.00, 0.17) 95% Confidence Interval 0.85, 1.63 -0.03, 0.30 0.69, 1.52 •
Slide 12: Time to 2-Point Decline in Motor-Language Score
Time to 2-Point Decline in Motor-Language Score • Cox proportional hazards model of time to unreversed 2-point decline in motor-language (ML) score or score of 0 – 9-fold reduction in likelihood of ML decline compared to matched natural history patients
Slide 13: Motor-Language Score Change from Baseline
Motor-Language Score Change from Baseline
Slide 14: Adverse Event Summary
Adverse Event Summary Baseline Age (years) Overall Overall AE Summary a <2 <3 ≥3 Common AEs a,b (N=14) (N=14) (N=5) (N=8) (N=6) Any AE, n (%) 5 (100%) 8 (100%) 6 (100%) 14 (100%) Pyrexia 12 (86%) Any AE Grade 1 5 (100%) 8 (100%) 6 (100%) 14 (100%) Upper respiratory tract infection 12 (86%) Any AE Gr
Slide 15: Serious Adverse Event Summary
Serious Adverse Event Summary Overall Overall SAEs SAEs • 40 serious adverse events (SAEs) (N=14) (N=14) Pyrexia 4 (29%) Hypoxia 1 (7%) reported in 12 subjects Hypersensitivity 2 (14%) Infection 1 (7%) • SAEs reported more than once Influenza 2 (14.%) Medical device hematoma 1 (7%) included: – pyrex
Slide 16: Summary and Conclusions
Summary and Conclusions • Interim results show that ICV-administered cerliponase alfa is generally well-tolerated and has an acceptable safety profile in this population, including subjects <3 years of age – As of the data cutoff (26 April 2020), 14 subjects had been enrolled and dosed with cerlipon
Slide 17: Acknowledgements
Acknowledgements • Children and families with CLN2 • Investigators and Study Teams disease • Study Sponsor: BioMarin Pharmaceutical Inc. • Batten disease patient advocacy • Authors: Angela Schulz1, Emily de los Reyes2, groups Nicola Specchio3, Paul Gissen4, Peter Slasor5, • DEM-CHILD Registry Shaile