Slide 1: A Prospective Trial of Vosoritide in Selected Genetic Causes of Short Stature
A Prospective Trial of Vosoritide in Selected Genetic Causes of Short Stature Despoina Galetaki, MD Endocrinology Fellow, PGYV Children’s National Hospital Washington, DC dgaletaki@childrensnational.org Investigator initiated study funded by BioMarin. NCT04219007 PI: Andrew Dauber (adauber@childrens
Slide 2: Financial Disclosures
Financial Disclosures: • The current study was funded by an investigator-initiated grant from BioMarin Pharmaceutical to Dr. Andrew Dauber. The company played no role in study design, conduct, data analysis, or abstract preparation. • No other disclosures
Slide 3: What is vosoritide?
What is vosoritide? Baron J et al. Short and tall stature: a new paradigm emerges. Nature Reviews Endocrinology 2015;11(12)735-46. Ornitz DM et al. Fibroblast Growth factor signaling in skeletal development and disease. Genes Dev. 2015;29(14):1463-1486.
Slide 4: Vosoritide for Selected Genetic Causes of Short Stature
Vosoritide for Selected Genetic Causes of Short Stature SHOX • Hypochondroplasia • CNP Deficiency • Heterozygous NPR2 mutation • RASopathy (Noonan Syndrome) • SHOX • Aggrecan Deficiency ACAN Ornitz DM et al. Fibroblast Growth factor signaling in skeletal development and disease. Genes Dev. 2015;29(1
Slide 5: 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 • Variants in one of the 6 categories • Absence of growth hormone deficiency • No concurrent treatment with GH (prior treatment is OK).
Slide 6: 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 7: Genetic Categories
Genetic Categories 2 1 7 26 8 12 Hypochondroplasia ACAN Noonan NPR2 NF1 Costello
Slide 8: Non-hypochondroplasia patients
Non-hypochondroplasia patients: Assessed for eligibility Total enrolled subjects N=30 (n=34) Age at enrollment in years, mean (range) 7.1 (3-11) 4 ineligible patients excluded due to height > -2 SD Age groups # (%) (2 Noonan, 1 NPR2, 1 ACAN) 3 to <5 y 6 (20%) 5 to <9y 18 (60%) Enrolled and Allocated
Slide 9: Growth Velocity Outcomes
Annualized growth velocity (cm/y) sc 10 15 0 5 re en in g G V (n=24) 4.5cm/y Annualized growth velocity (cm/y) sc 10 15 0 5 re en in m g G on V th 6 G V m on th (n=15) 6 8.5cm/y G V m m on th on th 12 G 12 V G V (n=11) 8.1cm/y NF1 Growth Velocity Outcomes: NPR2 ACAN Noonan sc Annualized growth veloc
Slide 10: Outcomes per condition: Height
Outcomes per condition: RASopathies NPR2 ACAN 0 0 0 -1 -2 -1 SD Heigh SD -2 -4 Height -2 -3 -6 -3 -4 -8 -5 -4 -10 screening day 1 month 6 month 12 screening day 1 month 6 month 12 screening day 1 month 6 month 12 VOS13 VOS22 VOS36 VOS37 VOS41 VOS03 VOS10 VOS15 VOS39 VOS44 VOS45 VOS5 VOS7 VOS30 VOS40
Slide 11: Safety Outcomes
Safety Outcomes: • Overall, well tolerated, no discontinuation due to AEs. • Injection site reactions are common (33% of patients, all self-resolved, grades 1 or 2) • No Grade 4 or 5 AE • 7 Grade 3 AE: 5 not related to treatment: o 1 T&A during observation period o 1 hospitalization for asthma attac
Slide 12: AEs of special interest
AEs of special interest: • No episodes of symptomatic hypotension Transient dizziness post injection reported in one subject, self-resolved without intervention • Echocardiograms were stable with no clinical concerns • Scoliosis reported in 7 patients: • 4 patients present prior to treatment (ACAN x
Slide 13: Conclusions
Conclusions • Preliminary results suggest a positive response (>3 cm/year increase) in all subgroups with interindividual variability • Well-tolerated with similar safety profile to previous reports in patients with achondroplasia • Unclear if genu valgum and scoliosis are related to the underlying
Slide 14: QUESTIONS?
QUESTIONS? Childrens National.