Pediatric achondroplasia: peptide analogue yields increased growth, mild side-effect profile

  • N Engl J Med

  • International Clinical Digest
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Takeaway

  • Treatment of pediatric achondroplasia with once-daily injections of the C-type natriuretic peptide analogue vosoritide yielded sustained increased growth velocity for 42 months with largely mild side-effects.

Why this matters

Key results

  • 100% of patients (35/35) experienced adverse events (AEs) in dose-finding and extension studies.
  • Serious AEs in 11% (4/35).
  • Antibody drug responses in 40% (14/35). 
  • 6 discontinued, 1 for an AE.
  • In initial 6 months on treatment, growth velocity increased dose-dependently in highest 3 dose cohorts, ranging from 1.28 (95% CI, 0.07-2.48) to 2.08 cm/year (95% CI, 0.30-3.87).
  • In all cohorts, velocities increased yearly (1.10-2.34 cm/year), sustained up to 42 months (data cutoff).
  • Proportional growth observed. 
  • “Nonserious and transient" BP changes.

Study design

  • 35 children (mean age, 7.6±1.7 years; 19 girls), 4 dose cohorts:
    • Cohort 1, n=8, 2.5 μg vosoritide/kg body weight, increased to 7.5 and then 15.0.
    • Cohort 2: n=8, 7.5 μg/kg body weight, increased to 15.0. 
    • Cohort 3: n=10, 15.0 μg/kg body weight.
    • Cohort 4: n=9, 30.0 μg/kg body weight.
  • Funding: BioMarin Pharmaceutical.

Limitations

  • Small numbers, uncontrolled trials.