Slide 1: Long-term height gain and maintenance of treatment effect in children with achondroplasia receiving vosoritide
OC7.4 Long-term height gain and maintenance of treatment effect in children with achondroplasia receiving vosoritide Julie E. Hoover-Fong1, Melita Irving2, Paul Harmatz3, Carlos A. Bacino4, Ian Sabir5, Hai Liu6, Richard Rowell6, Neil Lyon5, Alice Huntsman Labed5, Ravi Savarirayan7 1Johns Hopkins Uni
Slide 2: Conflict of Interest
CONFLICT OF INTEREST Ravi Savarirayan X I have the following potential conflicts of interest to report: X Research grants from BioMarin Pharmaceutical Inc X Consulting fees from Ascendis, BridgeBio Pharma, and BioMarin Pharmaceutical Inc Employment in the Industry Stockholder of a healthca
Slide 3: Achondroplasia is a genetic condition of impaired endochondral bone growth
Achondroplasia is a genetic condition of impaired endochondral bone growth Medical complications1 Functional challenges1 • Impaired physical functioning Neurologic Hydrocephalus Foramen magnum stenosis • Reduced mobility/gait Cervicomedullary compression Disproportionate Central sleep apnea • Access
Slide 4: Vosoritide efficacy and safety for achondroplasia is established with over a decade of data
Vosoritide efficacy and safety for achondroplasia is established with over a decade of data from clinical trials and the real world Vosoritide, the first approved Over a decade of clinical trials Vosoritide initiation is approved precision therapy for ACH, is a and real-world experience with in infa
Slide 5: Clinical benefits of early and continuous treatment from infancy to final adult height are unknown
Clinical benefits of early and continuous treatment from infancy to final adult height are unknown • No single clinical trial has followed an individual cohort for the entire growth period; however, overall growth benefit may be estimated with cross-sectional analyses of different studies that colle
Slide 6: Estimation of the cumulative additional clinical benefit
Estimation of the cumulative additional clinical benefit 111-208 111-302 Aim: Estimate cumulative additional growth vs natural history if treated from infancy until final adult height Mean AGV is similar from overlapping ages (5–9 years) across studies Mean interval AGV Additional growth Cumulative
Slide 7: Vosoritide improved AGV from 0.5 to years of age
Vosoritide improved AGV from 0.5 to 17 years of age Vosoritide-treated children with ACH have increased AGV across all ages compared with untreated children with ACH Males Females Interval age additional growth = treated AGV – natural history AGV 13 14 12 13 11 12 10 11 9 10 AGV (cm/year) AGV (cm/ye
Slide 8: Vosoritide from infancy provides additional cumulative growth beyond natural history
Vosoritide from infancy provides additional cumulative growth beyond natural history 26.4 cm (95% Cl, 22.9–29.8) 21.7 cm (95% Cl, 18.7–24.6) predicted additional growth at final predicted additional growth at final Males adult height Females adult height 30 30 25 25 Additional growth (cm) Additional
Slide 9: Conclusion
Conclusion Estimated long-term additional growth beyond natural history suggests early and continuous vosoritide treatment may maximize clinical benefits for children with ACH Over a decade of clinical trials and real-world experience of vosoritide has demonstrated that treated children have signifi
Slide 10: Cumulative growth with treatment from infancy is added evidence that early treatment initiation provides long-term benefits
Cumulative growth with treatment from infancy is added evidence that early treatment initiation provides long-term benefits Preventing complications Increased Functionality Neurological Improved mobility/gait Foramen magnum stenosis • In an observational study, vosoritide & sleep testing provided cl
Slide 11: Acknowledgments
Acknowledgments • Thank you to all trial participants, their families, study-site personnel, and investigators • Funding for this study was provided by BioMarin Pharmaceutical Inc. • Medical writing support was provided by Rachel Corrigan, PhD, of AlphaBioCom, a Red Nucleus company, and funded by Bi
Slide 12: Appendix
Appendix
Slide 13: Pooled clinical results from infancy until FAH
Pooled clinical results from infancy until FAH • Participants were pooled from the phase 3 study 111-301 (NCT03197766) active arm and its ongoing LTE 111-302 (NCT03424018) and the phase 2 study 111-206 (NCT03583697) active arm and its ongoing LTE 111-208 (NCT03989947) Data cut Feb 2024 • 119 childre
Slide 14: Participant characteristics at treatment initiation
Participant characteristics at treatment initiation 111-302 111-208 (N = 119) (N = 73) Mean (SD) age, years 9.18 (2.60) 2.63 (1.65) Min, max 5.1, 15.9 0.38, 6.0 Mean (SD) duration of treatment, days 1705.6 (386.4) 1328.7 (189.2) Min, max 618, 2565 1113, 1596 Male, n (%) 63 (52.9) 37 (50.7) 14 Max, m
Slide 15: AGV at any age interval is independent of time on therapy
AGV is at any age interval is independent of time on therapy In vosoritide-treated children with ACH pooled from 111-302 and 111-208, AGV is similar regardless of treatment duration Males Females 20 20 19 19 18 18 17 17 16 16 15 15 14 14 13 13 AGV (cm/year) AGV (cm/year) 12 12 11 11 10 10 9 9 8 8 7
Slide 16: Consistent AGV across clinical studies
Consistent AGV across 2 clinical studies AGV was similar in overlapping age intervals (5–9 years) from studies 111-208 and 111-302 • To demonstrate the potential benefits of long-term vosoritide treatment from age 0.5 years to final adult height, we used pooled data from phase 2 and phase 3 studies