A randomised, open-label, parallel group phase 2 study of antisense oligonucleotide therapy in acromegaly.
CONCLUSIONS: Baseline median IGF-I was 447 and 649 ng/mL in the once- and twice-weekly groups, respectivey. Compared to baseline, at week 14 twice-weekly ATL1103 resulted in a median fall in IGF-I of 27.8% (p=0.0002). Between cohort comparison at week 14 demonstrated the median fall in IGF-I to be 25.8% (p=0.0012) greater with twice-weekly dosing. In the twice-weekly cohort, IGF-I was still declining at week 14, and at week 21 remained lower than at baseline by a median of 18.7% (p=0.0005). Compared to baseline, by week 14 IGFBP3 and ALS had declined by a median of 8.9% (p=0.027) and 16.7% (p=0.017) with twice-weekly ATL1103; GH had increased by a median of 46% at week 14 (p=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 (p=0.027 and p=0.005), respectively. ATL1103 was well tolerated, although 84.6% of patients experienced mild to moderate injection-site reactions (ISR). This study provides proof-of-concept that ATL1103 is able to significantly lower IGF-I in patients with acromegaly.
PMID: 29789410 [PubMed - as supplied by publisher]
Source: European Journal of Endocrinology - Category: Endocrinology Authors: Trainer PJ, Newell-Price J, Ayuk J, Aylwin S, Rees DA, Drake W, Chanson P, Brue T, Webb SM, MontaƱana CF, Aller J, McCormack AI, Torpy DJ, Tachas G, Atley L, Ryder D, Bidlingmaier M Tags: Eur J Endocrinol Source Type: research