Positive long-term safety and efficacy data confirm the role of Mycapssa in the management of acromegaly patients.- Amryt.

The MPOWERED trial was designed to support the marketing authorization application for Mycapssa by the EMA which is currently under evaluation. Mycapssa is approved in the United States for long-term maintenance treatment in acromegaly patients who have responded to and tolerated treatment with injectable octreotide or lanreotide.

MPOWERED Phase III Trial – Open-Label Long-Term Safety & Efficacy Data : 60 patients that completed the 15 months core treatment phase elected to continue treatment with Mycapssa in the MPOWERED open label extension study. During the RCT 19 patients were treated with iSRLs and 35 were treated with Mycapssa . In addition, 6 patients were treated with a combination of Mycapssa and cabergoline. Key study outcomes included : i. 93%, 91% and 92% of patients completed year 1, 2 and 3 of the OLE, respectively, out of those that entered each year. ii. The average IGF-1 levels of enrolled patients were stably maintained within the normal limits at the end of the OLE period (median IGF-1 levels at Baseline and at the end of the OLE were 0.82 and 0.83 respectively). iii. 86%, 81% and 87% of all patients maintained their biochemical response at year 1, 2 and 3 of the OLE respectively, while utilizing a non-response imputation (any treatment discontinuation is regarded as no-response). iv. 94%, 90% and 93% of patients maintained their biochemical response at year 1, 2 and 3 of the OLE respectively, while utilizing the last observed carried forward (LOCF) imputation in patients treated with Mycapssa monotherapy. v. Of patients switching from iSRLs to Mycapssa during the OLE, 47% reported excellent or very good symptomatic control (5% and 42% respectively) at the end of the Randomized Control Treatment (RCT), increasing to 79% at the end of the OLE (32% and 47% respectively). vi. 58% had at least 3 active acromegaly symptoms on iSRLs at the end of the RTC decreasing to 37% at the end of the OLE after switching to Mycapssa. vii. In addition, patients treated with iSRLs during the RCT improved when treated with Mycapssa in the OLE on the Emotional, GI interference, Treatment convenience and Treatment satisfaction domain scores of the Acromegaly treatment satisfaction questionnaire (Acro-TSQ, a validated acromegaly patient reported outcome tool) viii. Acromegaly patients were exposed to Mycapssa during the OLE for a median treatment duration of 2.2 years and a maximal exposure of 3.5 years. Including the 15 months core treatment phase, 10 patients were treated for more than 4 years and 22 patients for more than 3 years. ix. Patients in the OLE demonstrated a median compliance rate of 99% over this period of time.

The long-term safety profile of Mycapssa during the OLE, was consistent with the safety profile observed during the core study (Run-in plus RCT) with no new safety signals with long- term exposure.

About the MPOWERED Phase III Trial : The MPOWERED trial was a global, randomized, open-label and active-controlled, 15-month trial intended to support approval of Mycapssa in the European Union. Chiasma/Amryt completed enrollment of 146 adult acromegaly patients into the trial in June 2019, of which 92 patients who were deemed responders to octreotide capsules per the protocol following a six-month run-in were randomized to either octreotide capsules (n=55) or iSRLs (octreotide long-acting release or lanreotide autogel) (n=37). These patients were then followed for an additional nine months in the randomized controlled treatment (RCT) phase. At the end of the RCT phase patients were provided the option to continue into an open label phase and receive Mycapssa.

The study met its primary non-inferiority endpoint. 91% of patients on Mycapssa maintained insulin-like growth factor 1 (IGF-1) response (95% CI = 80%, 97%), throughout the RCT, compared to 100% on iSRLs (95% CI = 91%, 100%). Response was defined as the time-weighted average of IGF-1 <1.3 x upper limit of normal (uln) during the 9-month rct phase.></1.3>