Abstract
BACKGROUND: Oral octreotide capsules (OOC) are an approved treatment option in the United States for patients with acromegaly who have previously responded to injectable somatostatin receptor ligands (iSRLs). Safety and efficacy of OOC was demonstrated in the CHIASMA OPTIMAL trial (NCT03252353), showing maintenance of response and a safety profile consistent with iSRLs. Results from the first 48 weeks of the open-label extension (OLE) of this trial suggested that this effect was durable for the long-term. OBJECTIVE: Report efficacy and safety through the second year of the OLE. METHODS: Eligible patients had the option to enroll in the OLE of CHIASMA OPTIMAL following the double-blind placebo-controlled (DPC) period. Endpoints in the second year of the OLE were exploratory, including: the proportion of patients completing week 96 of the OLE, the proportion of responders entering year 2 who remained responders of those with evaluable data (response defined as average Insulin-like growth factor I [IGF-I] ≤1. 0 × upper limit of normal [ULN] at last 2 visits between weeks 84-96), and changes in IGF-I and growth hormone (GH) from OLE baseline to OLE week 96 in those completing the DPC period on study drug. RESULTS: Thirty-two patients from the core period (DPC groups: n=14, placebo; n=18, OOC) entered year 2 of the OLE and 31 (97%) completed. OOC dose at the start of year 2 was 40 mg/d, n=3; 60 mg/d, n=8; and 80 mg/d, n=21. For patients who had non-missing data response rate at 96 weeks was 100% (17/17) for patients who entered year 2 as responders, and 93% (27/29) for patients overall. Mean IGF-I for patients from the OOC group who completed the DPC period on study drug (n=14) was 0.81 × ULN at baseline of OLE and 0.78 × ULN at week 96, (change, −0. 03 × ULN). Mean GH (n=12) was 0.43 ng/mL and 0.44 ng/mL at baseline and week 96, respectively (change, 0. 01 ng/mL). For patients who completed the DPC period on placebo (n=8), mean IGF-I was 1. 05 and 0.77 × ULN at OLE baseline and week 96, respectively (change, −0.28); mean GH (n=5) was 1. 06 and 0.34 ng/mL at OLE baseline and week 96, respectively (change, −0.72 ng/mL). Median exposure to OOC was 2.1 years, with exposure >3 years for 5 patients. Throughout the OLE period, 50% of patients experienced adverse events (AEs), with no serious AEs. One patient discontinued treatment due to an AE (headache). The safety profile was consistent with that reported for OOC; no new patterns were observed with increased exposure. CONCLUSION: Maintenance of biochemical response with OOC was durable up to 96 weeks. The safety profile of OOC was consistent with that of iSRLs. No new safety signals were observed with increased exposure duration. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.