BioMarin Pharmaceutical Inc. · NASDAQ:BMRN
BioMarin Pharmaceutical — Technical Presentation (April 2024)
20 slides from BioMarin Pharmaceutical's technical presentation, Apr 11, 2024
Slide 1: Vosoritide Increases Growth Velocity in Hypochondroplasia: Phase 2 Trial Results
Vosoritide Increases Growth Velocity in Hypochondroplasia: Phase 2 Trial Results Andrew Dauber, MD MMSc, Anqing Zhang PhD, Roopa Kanakatti Shankar MBBS, Kimberly Boucher RN, Tara McCarthy BSPH, Niusha Shafaei MS, Raheem Seaforth BA, Meryll Grace Castro MS, Niti Dham MD, Nadia Merchant MD This study
Slide 2: Hypochondroplasia Overview
Hypochondroplasia Overview • Autosomal dominant skeletal dysplasia • Activating variants in FGFR3 – p.Asn540Lys most common • Prevalence estimated between 1 in 15,000-40,000 • Disproportionate short stature • Mean adult height of ~131 cm for females and 144 cm for males1 • No approved therapies 2 1.
Slide 3: Baron J et al. Short and tall stature: a new paradigm emerges. Nature Reviews
Baron J et al. Short and tall stature: a new paradigm emerges. Nature Reviews Endocrinology 2015;11(12)735-46. 3 Ornitz DM et al. Fibroblast Growth factor signaling in skeletal development and disease. Genes Dev. 2015;29(14):1463-1486.
Slide 4: Savarirayan et al. Lancet 2020; 396:684-92.
Savarirayan et al. Lancet 2020; 396:684-92. 4
Slide 5: 2nd Year Results: Sustained increased in growth velocity and improvement in body proportions
2nd Year Results: Sustained increased in growth velocity and improvement in body proportions Savarirayan et al. Genetics in Medicine, 2021;2:1-5. 5
Slide 6: Vosoritide for Selected Genetic Causes of Short Stature
Vosoritide for Selected Genetic Causes of Short Stature SHOX • Hypochondroplasia • CNP Deficiency • Heterozygous NPR2 mutation • RASopathy • SHOX • Aggrecan Deficiency ACAN 6 Ornitz DM et al. Fibroblast Growth factor signaling in skeletal development and disease. Genes Dev. 2015;29(14):1463-1486.
Slide 7: Inclusion Criteria and Study Design
Inclusion Criteria and Study Design • Age >3 years 0 days AND <10 years 364 days for males, <9 years 364 days for females • Pre-pubertal • Patient height <-2.25 SDS. • Mutation in one of 6 categories • Absence of growth hormone deficiency • No concurrent treatment with GH (prior Rx is OK). • No othe
Slide 8: Study Outcomes
Study Outcomes Primary study endpoints: The exploratory study endpoints • Incidence of adverse events include: • ∆ growth velocity at 12 months • Pharmacokinetic studies • ∆ height SDS at 12 months • Pharmacodynamic markers Secondary study endpoints: • Bone mineral density • Body proportions • Effec
Slide 9: Genetic Categories
Genetic Categories 2 1 7 26 8 12 Hypochondroplasia ACAN Noonan NPR2 NF1 Costello 9
Slide 10: Enrollment
Hypochondroplasia Subjects Only Total enrolled subjects N=24 Assessed for eligibility (n =27) Age at screening (years) Enrollment mean (SD); median (IQR) 5.86 (2.29); 5.55 (2.39) Excluded (n =1) Height above -2.25 SD (n =1) Age group # (%) 3 to <5 year 10 (41.7%) 5 to <9 year 11 (45.8%) Entered Obse
Slide 11: Safety
Safety • 83% of subjects had injection site reactions – All grade 1 or 2 – All self-resolved without intervention • No subjects discontinued treatment due to an AE • 1 SAE unrelated to vosoritide – viral induced ITP • 1 episode of syncope with documented normal blood pressure • No episodes of sympto
Slide 12: Hypochondroplasia – Growth Velocity Outcomes
Hypochondroplasia – Growth Velocity Outcomes Annualized Growth Velocity Annualized Growth Velocity Z-score 1.81 cm/year increase in AGV; 2.26 SD increase in AGV Z-score 12
Slide 13: Individual Growth Velocity Curves
Individual Growth Velocity Curves 13
Slide 14: Growth Velocity Subgroup Analysis
Growth Velocity Subgroup Analysis Annualized growth velocity (cm/yr) Observation Period Treatment Period Difference Between Treatment Two-sided Mean (SD) Mean (SD) and Observation (95% CI) p value Age 3 to <5 Year 5.97 (1.38) 7.32 (0.79) 1.35 (0.23, 2.47) 0.02 (N=10) Age 5 to <9 Year 4.27 (0.75) 6.9
Slide 15: CDC Height SDS Outcomes
CDC Height SDS Outcomes -2.91 -3.06 -3.29 -3.28 15
Slide 16: Hypochondroplasia Specific Height SDS Outcomes
Hypochondroplasia Specific Height SDS Outcomes 0.03 SD change during observation vs 0.41 SD change during treatment 16 Analysis used growth charts by Cheung MS et al, AJMG Part A 2024.
Slide 17: Pharmacodynamic Biomarkers
Pharmacodynamic Biomarkers Collagen X Biomarker Urine cGMP Response www.acmg.net 17
Slide 18: Secondary Outcomes
Secondary Outcomes • No change in bone age/chronological age – 0.78 at Day 1 vs 0.79 at Month 12 (p=0.67) • Sitting height ratio showed minor decrease over 1 year of treatment but not significant when adjusted for age/sex. • No change in arm span minus height. • No change in parent reported quality
Slide 19: Conclusions
Conclusions • Vosoritide increases growth velocity in children with hypochondroplasia to a similar degree as has been seen in achondroplasia. • Safety profile was relatively benign and consistent with prior reports. • Additional analyses are ongoing to examine factors that may predict response. • Ou
Slide 20: Acknowledgements
Acknowledgements We would like to thank the patients and their families for their participation. We would like to thank the staff of the clinical research center and investigational pharmacy at Children’s National Hospital. Interested in enrolling in studies? – Contact me at adauber@childrensnationa
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