Slide 1: Real-world clinical outcomes of intraventricular cerliponase alfa in CLN2 disease
Real-world clinical outcomes of intraventricular cerliponase alfa in CLN2 disease: Comparison with a historical cohort Angela Schulz1, Christoph Schwering1, Eva Wibbeler1, Lena M Westermann1, Luca Hagenah1, Susanne Lezius2, Peter Slasor3, Pascal Reisewitz3, Miriam Nickel1 1Children’s Hospital, Unive
Slide 2: Conflict of interest disclosure
Conflict of interest disclosure • Angela Schulz has received research grants from BioMarin Pharmaceutical Inc.; honoraria for speaker fees from BioMarin Pharmaceutical Inc., and for consultations from Regenxbio Inc. and Neurogene Inc.; and was Principal Investigator in the BMN 190 clinical trials fu
Slide 3: CLN2 disease: A rare and rapidly progressive childhood neurodegenerative disorder
CLN2 disease: A rare and rapidly progressive childhood neurodegenerative disorder CLN2 disease is a rare, genetic, neurodegenerative disorder of childhood caused by deficient tripeptidyl peptidase 1 (TPP1) enzyme activity1–3 Deficient TPP1 activity results in the intralysosomal accumulation of autof
Slide 4: CLN2 disease is associated with rapid decline in motor and language function
CLN2 disease is associated with rapid decline in motor and language function DEM-CHILD database, natural history cohort (2002–2016) (N = 41) 6 Sum of motor and language score 5 4 Motor and language domains are each scored from 3 to 0, with lower scores indicating more 3 extensive impairment of funct
Slide 5: Cerliponase alfa
Cerliponase alfa • Cerliponase alfa is a recombinant human form of TPP1 enzyme and was approved for the treatment of CLN2 disease in the US and EU in 20171–4 – In clinical trials, intracerebroventricular administration of cerliponase alfa was shown to slow decline in motor and language function comp
Slide 6: Analysis methods
Analysis methods Patients • Enrolled in the DEM-CHILD database (international NCL patient registry) (NCT04613089) with confirmed diagnosis of CLN2 disease by genetic and enzyme testing Treated patients: initiated cerliponase alfa outside of clinical trials and had at least 6 months of follow-up on t
Slide 7: Patient characteristics
Patient characteristics Patients matched on baseline age and ML score Natural history Cerliponase alfa-treated N = 21 N = 21 Sex n (%) Female 5 (24) 11 (52) Male 16 (76) 10 (48) Age at baseline, years Mean (SD) 4.7 (1.9) 4.7 (1.9) Median [min, max] 4.5 [0.7, 9.9] 4.5 [0.7, 9.9] Baseline ML score Mea
Slide 8: Rate of decline in ML score
Rate of decline in ML score Patients matched on baseline age and ML score Natural history Cerliponase alfa-treated N = 21 N = 21 Rate of decline in ML score, points per 48 weeks Mean (SD) 1.88 (1.45) 0.46 (0.43) Median [min, max] 1.66 [0.00, 5.60] 0.44 [0.00, 1.33] 95% CI 1.22, 2.54 0.26, 0.64 Mean
Slide 9: Time to unreversed 2-point decline or score 0 in ML domains
Time to unreversed 2-point decline or score 0 in ML domains Patients matched on baseline age and ML score HR (95% CI): 0.08 (0.02, 0.28) p ≤ 0.0001 Cerliponase alfa-treated Natural history Cerliponase alfa-treated (n) Natural history (n) Time (months) 9 CI, confidence interval; HR, hazard ratio; ML,
Slide 10: Treatment-related adverse events
Treatment-related adverse events All cerliponase alfa-treated patients (N = 24) All treatment-related AEs Treatment-related AEs resulting in hospitalization N = 24 N = 24 Incidence Events Rate Incidence Events Rate n (%) (events/100 PY) n (%) (events/100 PY) Any treatment-related AE 16 (66.7) 75 13.
Slide 11: Conclusions
Conclusions • Cerliponase alfa treatment slowed deterioration in motor and language function in children with CLN2 disease in a real-world setting – These results from the real-world setting support efficacy findings from cerliponase alfa clinical trials • No new safety signals were identified – Tre
Slide 12: Acknowledgments
Acknowledgments • Medical writing services were provided by Phoebe Emson, MSc of Adelphi Communications Ltd (Macclesfield, UK) funded by BioMarin Pharmaceutical Inc. (CA, USA) in accordance with Good Publication Practice (GPP2022) 12
Slide 13: Time to unreversed score of 0 in ML domains
Time to unreversed score of 0 in ML domains Patients matched on baseline age and ML score HR (95% CI): 0.07 (0.01, 0.40) p = 0.003 Cerliponase alfa-treated Natural history Cerliponase alfa-treated (n) Natural history (n) Time (months) 13 CI, confidence interval; HR, hazard ratio; ML, motor-language;
Slide 14: Rate of decline in motor score
Rate of decline in motor score Patients matched on baseline age and ML score Natural history Cerliponase alfa-treated N = 21 N = 21 Rate of decline in motor score, points per 48 weeks n = 20 n = 20 Mean (SD) 0.99 (0.75) 0.23 (0.28) Median [min, max] 1.02 [0.00, 2.40] 0.11 [0.00, 0.79] 95% CI 0.64, 1
Slide 15: Rate of decline in language score
Rate of decline in language score Patients matched on baseline age and ML score Natural history Cerliponase alfa-treated N = 21 N = 21 Rate of decline in language score, points per 48 weeks n = 19 n = 18 Mean (SD) 1.04 (0.96) 0.16 (0.28) Median [min, max] 0.80 [0.00, 3.73] 0.00 [0.00, 0.72] 95% CI 0
Slide 16: Sensitivity analysis: Rate of decline in ML score
Sensitivity analysis: Rate of decline in ML score Patients matched on baseline age, ML score, and genotype (3-criteria match) Natural history Cerliponase alfa-treated N = 18 N = 18 Rate of decline in ML score, points per 48 weeks Mean (SD) 2.07 (1.61) 0.49 (0.43) Median [min, max] 2.18 [0.00, 5.60]