SAT-433 Long-Acting Pasireotide Provides Clinical Benefit to Patients with Uncontrolled Acromegaly over Continued Treatment with First‑Generation Somatostatin Analogues (SSAs): Results from Phase 3b, Open-Label Study

Background: In a 24-week, Phase 3 study (PAOLA), long-acting pasireotide demonstrated superior efficacy (GH <2.5 µg/L and IGF-1 <ULN) over continued treatment with long-acting octreotide/lanreotide in pts with uncontrolled acromegaly (Gadelha MR, et al. Lancet Diabetes Endocrinol. 2014;2:875-884). An earlier (3 months) switch to long-acting pasireotide and the current criteria for biochemical control, i.e. GH <1 μg/L and IGF-1 <ULN, are considered in the present phase 3b study. This study (clinicaltrials.gov: NCT02354508) evaluated the efficacy (GH <1 μg/L and IGF-1 <ULN) and safety of long‑acting pasireotide in pts with uncontrolled acromegaly despite ≥3 months of treatment with maximal approved doses of first-generation SSAs. Methods: Adults with uncontrolled acromegaly (mean GH [mGH] ≥1 µg/L and IGF-1 >1.3xULN) despite ≥3 months of treatment with maximal approved doses of long-acting octreotide/lanreotide received open-label long-acting pasireotide 40 mg/28 days. Pasireotide dose could be up titrated to 60 mg/28 days after week 12 if the biochemical control was not achieved or down titrated to 20 mg/28 days or 10 mg/28 days for tolerability. Primary endpoint: proportion of pts with mGH <1 μg/L and IGF-1 <ULN at week 36 overall and by screening mGH (1.0-2.5 μg/L and >2.5 μg/L). Results: 123 pts received long-acting pasireotide: median age, 43.0 years (range, 22-76); female, 50.4%; baseline median (range) mGH, 5.4 µg/L (1.2-195.5) and IGF-1, 2.3xULN (1.4-7.9); prediabetic/diabetic at baseline, n=112 (91.1%). The median duration of exposure to pasireotide was 36.0 weeks (median dose intensity, 53.3 mg/month). Overall, 18 pts (14.6% [95%CI, 8.9-22.1]) achieved biochemical control at week 36 (primary endpoint); 12 (42.9% [95%CI, 24.5-62.8]) and 6 pts (6.4% [95%CI, 2.4-13.4]) by screening mGH levels of 1.0 to 2.5 µg/L (n=28) and >2.5 µg/L (n=94), respectively. At week 36, 23 (18.7%), 16 (57.1%) and 7 pts (7.4%) had GH <1 µg/L; and 38 (30.9%), 14 (50.0%) and 24 pts (25.5%) had IGF-1 <ULN overall and by screening mGH levels of 1.0 to 2.5 µg/L and >2.5 µg/L, respectively. The median percentage decreases in mGH and standardized IGF-1 from baseline to week 36 were 56.8% and 42.8%. The most common AEs (>15%) regardless of study drug relationship were hyperglycemia (43.1%), diabetes mellitus (22.0%), and diarrhea (15.4%). Hyperglycemia-related AEs suspected to be drug related occurred in 81 pts (66%) overall and 4 of 11 pts (36.4%) who were nondiabetic at baseline. A total of 10 pts (8.1%) discontinued treatment either because of AEs (n=4; 3.3%) or unsatisfactory therapeutic effect (n=3; 2.4%), or consent withdrawal (n=3; 2.4%). Conclusions: In pts with uncontrolled acromegaly, switching to long-acting pasireotide after ≥3 months of treatment with first-generation SSAs provided biochemical control (mGH <1.0 μg/L and IGF-1 <ULN) in 15% of all pts and 43% of pts with lower screening mGH (1.0-2.5 µg/L).