A randomised, open-label, parallel group phase 2 study of antisense oligonucleotide therapy in acromegaly

Abstract

Baseline median IGF-I was 447 and 649 ng/mL in the once- and twice-weekly groups respectively. Compared to baseline, at week 14, twice-weekly ATL1103 resulted in a median fall in IGF-I of 27.8% (<i>P</i> = 0.0002). Between cohort comparison at week 14 demonstrated the median fall in IGF-I to be 25.8% (<i>P</i> = 0.0012) greater with twice-weekly dosing. In the twice-weekly cohort, IGF-I was still declining at week 14, and remained lower at week 21 than at baseline by a median of 18.7% (<i>P</i> = 0.0005). Compared to baseline, by week 14, IGFBP3 and ALS had declined by a median of 8.9% (<i>P</i> = 0.027) and 16.7% (<i>P</i> = 0.017) with twice-weekly ATL1103; GH had increased by a median of 46% at week 14 (<i>P</i> = 0.001). IGFBP3, ALS and GH did not change with weekly ATL1103. GHBP fell by a median of 23.6% and 48.8% in the once- and twice-weekly cohorts (<i>P</i> = 0.027 and <i>P</i> = 0.005) respectively. ATL1103 was well tolerated, although 84.6% of patients experienced mild-to-moderate injection-site reactions. This study provides proof of concept that ATL1103 is able to significantly lower IGF-I in patients with acromegaly.