Biomarin Pharmaceutical Inc. · NASDAQ:BMRN
Biomarin Pharmaceutical — Technical Presentation (2022)
16 slides from Biomarin Pharmaceutical's technical presentation, 2022
Slide 1: Seizures in Children with CLN2 Disease Receiving Cerliponase Alfa for >5 Years
Seizures in Children with CLN2 Disease Receiving Cerliponase Alfa for >5 Years Miriam Nickel, MD Angela Schulz, MD, PhD University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Slide 2: Cerliponase Alfa for the Treatment of CLN2 Disease
Cerliponase Alfa for the Treatment of CLN2 Disease • Cerliponase alfa is a recombinant human form of TPP1 enzyme (rhTPP1)1 approved for the treatment of CLN2 disease in the US and EU in 2017, and subsequently in a number of other countries worldwide CATHETER – Administered through an implanted Rickh
Slide 3: Cerliponase Alfa: 190-201/202 Study Design
Cerliponase Alfa: 190-201/202 Study Design 190-201: Phase 1/2 study 190-202: Open-label extension N=24 (age ≥3 years) N=23 (enrolled from 190-201) Dose escalation phase followed by Up to 240 weeks (300 mg qow) 48-week stable dose period (300 mg qow) 6-month safety follow up period (Clinicaltrials.go
Slide 4: Efficacy Assessment: CLN2 Disease Clinical Rating Scale
Efficacy Assessment: CLN2 Disease Clinical Rating Scale Motor Score Language Score Walks normally 3 Normal 3 Frequent falls, ataxia, independent walk >10 steps 2 Loss of words, intelligible but abnormal speech 2 No unaided gait 1 Some comprehension, mostly unintelligible speech 1 Immobile, mostly be
Slide 5: Combined Motor-Language Score as Primary Outcome
CLN2 Disease Clinical Rating Scale: Combined Motor-Language Score as Primary Outcome Motor Score Language Score Walks normally 3 Normal 3 Frequent falls, ataxia, independent walk >10 steps 2 Loss of words, intelligible but abnormal speech 2 No unaided gait 1 Some comprehension, mostly unintelligible
Slide 6: 190-201/202 Primary Efficacy: Decline in Motor-Language Score
190-201/202 Primary Efficacy: Decline in Motor-Language Score Treated subjects were significantly less likely than natural history controls to have an unreversed 2- point decline or a score of 0 in the combined motor-language domains
Slide 7: 190-201/202 Primary Efficacy: Decline in Motor-Language Score
190-201/202 Primary Efficacy: Decline in Motor-Language Score Treated subjects were significantly less likely than natural history controls to have an unreversed 2- point decline or a score of 0 in the combined motor-language domains Rate of Decline in ML Score Natural History 190-201/202 Difference
Slide 8: Seizure Domain as Exploratory Outcome
CLN2 Disease Clinical Rating Scale: Seizure Domain as Exploratory Outcome Motor Score Language Score Walks normally 3 Normal 3 Frequent falls, ataxia, independent walk >10 steps 2 Loss of words, intelligible but abnormal speech 2 • Seizures No unaided gait present a significant burden throughout 1 C
Slide 9: 190-201/202: Seizure Assessments
190-201/202: Seizure Assessments • Incidence of seizures in subjects treated with cerliponase alfa in 190-201/202 was assessed as follows: – Change from baseline in seizure domain score of CLN2 clinical rating scale compared to natural history controls – Number of treated subjects reporting ≥1 adver
Slide 10: Change from Baseline in Seizure Domain Score
190-201/202: Change from Baseline in Seizure Domain Score Mean (SD) seizure score increased* from 1.7 (1.2) at baseline to 2.4 (0.8) at week 289 in treated subjects and decreased from 1.7 (1.1) to 0.7 (1.2) in natural history controls. *Increase in seizure domain score represents decrease in seizure
Slide 11: Change from Baseline in Seizure Domain Score
190-201/202: Change from Baseline in Seizure Domain Score Change in Seizure Domain Score (N=23) (Baseline to Last Assessment), n (%) +3 (improvement) 4 (17.4) At the last assessment of the 300 +2 4 (17.4) mg dosing period, 12 subjects (52.2%) showed improvement in +1 4 (17.4) seizure score compared
Slide 12: Overall Summary of Adverse Events
190-201/202: Overall Summary of Adverse Events Summary of AEs Subjects (N=24), n (%) • Most AEs were Grade 1 or 2 in Any AE 24 (100) severity Any AE considered related to study drug 23 (96) • All AEs resolved spontaneously Any AE leading to: or with appropriate medical Dose interruption 15 (63) mana
Slide 13: Convulsions Adverse Events
190-201/202: Convulsions Adverse Events Summary of Convulsions AEs a Subjects (N=24), n (%) • 23 subjects experienced a total of Any convulsions AE 23 (96) 693 convulsions AEs: most were Grade Any convulsions AE considered related to 12 (50) 1 or 2 in severity study drug Any convulsions SAE 5 (21) A
Slide 14: Convulsions Adverse Events over Study Follow-Up
190-201/202: Convulsions Adverse Events over Study Follow-Up The proportion of treated subjects reporting ≥1 AE of convulsions declined from 88% (n=21) in weeks 0-24 to 59% (n=13) in weeks >216 Represents AEs mapping to the Convulsions Standardized MedDRA Query
Slide 15: Conclusions
Conclusions • These results suggest that there may be a reduction in the incidence of seizures over time in subjects receiving cerliponase alfa treatment • Further evaluation will be needed to assess the impact of disease progression, concurrent illness, and anti-seizure medication use, and to delin
Slide 16: 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
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