Safety Results From MPOWERED, a Phase 3 Trial of Oral Octreotide Capsules in Adults With Acromegaly

Background: Injectable somatostatin receptor ligands (iSRLs) have been a mainstay in acromegaly treatment. Oral octreotide capsules (OOC; MYCAPSSA(®)) were recently approved in the United States. Results from the placebo-controlled CHIASMA OPTIMAL and open-label CH-ACM-01 studies showed an OOC safety profile consistent with that of iSRLs with no new or unexpected safety signals. Results of the MPOWERED trial have enabled a comparison of OOC safety and efficacy with iSRLs. Methods: To enter MPOWERED, patients must have the following: acromegaly diagnosis, biochemical control of acromegaly (insulin-like growth factor I <1.3 × upper limit of normal; mean integrated growth hormone <2.5 ng/mL), and ≥6 months’ iSRLs treatment (octreotide or lanreotide). Eligible patients entered a 26-week Run-in phase to determine the effective OOC dose; responders at week 24 then entered a 36-week randomized controlled treatment (RCT) phase receiving OOC or iSRLs. Safety was monitored as adverse events (AEs) in both arms throughout the trial, including the RCT. Results: In the RCT, incidence of treatment-emergent adverse events (TEAEs) was similar between groups; 39 patients (70.9%) in the OOC group and 26 (70.3%) in the iSRL group had ≥1 TEAE. 19 patients (34.5%) in the OOC and 15 (40.5%) in the iSRL group had treatment-related TEAEs. Occurrence was similar for serious AEs (OOC, 5.5%; iSRL, 8.1%) as well as TEAEs classified as severe (OOC, 9.1%; iSRL, 10.8%). One patient in the OOC group discontinued due to a TEAE. The most common gastrointestinal TEAEs were flatulence (OOC, 25.5%; iSRL, 21.6%), nausea (OOC, 20.0%; iSRL, 8.1%), diarrhea (OOC, 10.9%; iSRL, 13.5%), abdominal pain (OOC, 9.1%; iSRL, 8.1%), and constipation (OOC, 5.5%; iSRL, 13.5%). AEs of interest were infrequent, including cholelithiasis (OOC, n=0; iSRL, n=1 [2.7%]) and secondary hypothyroidism (OOC, n=1 [1.8%]; iSRL, n=0). In the iSRL group, 32.4% of patients reported injection site reactions (ISRs) during the RCT, and 47% of patients reported ISRs as part of the Acromegaly Treatment Satisfaction Questionnaire, a newly validated patient-reported outcome tool.(1) Conclusion: Safety results from MPOWERED align with prior trials, showing that the OOC safety profile is consistent with that of iSRLs as well as the acromegaly disease burden. No new or unexpected safety signals were identified during the trial. Safety results were mostly similar between OOC and iSRLs, although patients in the OOC group did not experience any ISRs. (1)Fleseriu M, et al. Pituitary. 2020 Aug;23(4):347-358.