Combination therapy with growth hormone and vosoritide for achondroplasia

Abstract

Achondroplasia (ACH), one of the most common skeletal dysplasia causing disproportionate short stature, has approved treatments in Japan including GH, and the C-type natriuretic peptide analog, vosoritide. We report three ACH patients treated with combination GH-vosoritide therapy. All patients were diagnosed with ACH confirming the heterozygous pathogenic variant (p.Gly380Arg) in FGFR3 gene. GH therapy was initiated at 2.9–5.9 yr of age (growth velocity [GV], 2.6–4.7 cm/yr), and improved GV to 5.9–6.9 cm/yr at 1 yr post-treatment. Treatment was changed to vosoritide monotherapy at 9.1–10.8 yr with GV of 4.5–5.1 cm/yr in the last yr before transition. GV decreased within 3 mo after transition from GH to vosoritide but recovered by year-end, and GV consequently increased to 5.2–6.1 cm/yr by 1 yr of vosoritide monotherapy. Subsequent combination GH-vosoritide therapy for 1 yr further improved GV to 5.8–7.2 cm/yr. These clinical cases suggested that the combination therapy may be a possible treatment option. Since several new therapeutic candidates have been progressing through clinical trials and are likely to appear in clinical practice, an era might have come in which the best combination of various therapeutic agents will be chosen.