THU054 A Post Hoc Analysis Of The Phase IV B2219 Study To Determine Predictive Factors For Hyperglycemia During Treatment With Pasireotide
Authors: Samson Susan Leanne , Bolanowski Marek , Zhang Shao-Ling , Yu Yerong , Witek Przemysław , Kietsiriroje Noppadol , Piacentini Andrea , Pedroncelli Alberto M , Feldt-Rasmussen Ulla 
Published: October 2023

Disclosure: S.L. Samson: Consulting Fee; Self; Novartis Pharmaceuticals, Chiasma. M. Bolanowski: Grant Recipient; Self; Amryt, Recordati, Pfizer, Inc., Novartis Pharmaceuticals, Ipsen, IBSA, Teva Pharmaceutical Industries Ltd., Berlin Chemie. Speaker; Self; Amryt, Recordati, Pfizer, Inc., Novartis Pharmaceuticals, Ipsen, IBSA, Teva Pharmaceutical Industries Ltd., Berlin Chemie. S. Zhang: None. Y. Yu: None. P. Witek: Grant Recipient; Self; Novartis Pharmaceuticals, Ipsen, Recordati, Novo Nordisk, Xeris Pharmaceuticals (Strongbridge), Lilly USA, LLC. Speaker; Self; Novartis Pharmaceuticals, Ipsen, Recordati, Novo Nordisk, Xeris Pharmaceuticals (Strongbridge), Lilly USA, LLC. N. Kietsiriroje: None. A. Piacentini: Employee; Self; Recordati. A.M. Pedroncelli: Employee; Self; Recordati. U. Feldt-Rasmussen: Advisory Board Member; Self; Novartis Pharmaceuticals, Recordati, Novo Nordisk, Xeris Pharmaceuticals (Strongbridge). Grant Recipient; Self; Ipsen, Recordati, Novo Nordisk. Speaker; Self; Ipsen, Recordati, Novo Nordisk.

Introduction: Pasireotide efficacy and safety in persons with acromegaly or Cushing’s disease (CD) is confirmed in a comprehensive clinical trial program. Pasireotide-induced hyperglycemia events, expected based on the drug’s mechanism of action, are manageable with low rates of treatment discontinuation. To advance knowledge on pasireotide-induced hyperglycemia management, a prospective randomized Phase IV study (B2219, NCT02060383) was conducted. This secondary analysis assessed factors that might predict development of pasireotide-induced hyperglycemia. Methods: In B2219, participants (Pts) with acromegaly or CD who did not need therapy for hyperglycemia or were managed with metformin alone entered the non-randomized observational arm. Pts who developed hyperglycemia not managed with metformin alone were randomized to incretin-based therapy or insulin. This analysis evaluated Pts according to whether therapy for hyperglycemia during pasireotide treatment was needed. Logistic regression analyses evaluated quantitative and qualitative predictive factors associated with pasireotide-induced hyperglycemia. Results: Of 190 Pts with acromegaly and 59 with CD, 88 and 15, respectively, did not need antihyperglycemic medication during pasireotide treatment; Pt characteristics were generally balanced across subgroups at study baseline (BL). Most Pts who did not develop hyperglycemia had a mean age of &lt;40 years (acromegaly 62.5%, CD 86.7%), BL glycated hemoglobin (HbA1c) &lt;6.5% (acromegaly 98.9%, CD 100.0%) and BL fasting plasma glucose (FPG) &lt;100 mg/dL (acromegaly 76.1%, CD 100.0%). Age (odds ratio [OR] 1.0, 95% CI 1.0−1.1), BL HbA1c (OR 3.5, 95% CI 1.3−9.9) and prediabetes or diabetes conditions (OR 3.0, 95% CI 1.2−7.6) were identified as risk factors associated with pasireotide-induced hyperglycemia in Pts with acromegaly. BL FPG (OR 1.2, 95% CI 1.0−1.3) was associated with increased risk of pasireotide-induced hyperglycemia in Pts with CD. Overall, adverse events (AEs) of hyperglycemia and diabetes mellitus (investigator reported) occurred in 21.1% and 14.2% of Pts with acromegaly and 28.8% and 11.9% of Pts with CD, respectively. More Pts who had diabetes or prediabetes conditions at BL had hyperglycemia-related AEs than Pts with normal glucose levels. Hyperglycemia-related AEs were managed with antihyperglycemic medication (acromegaly 26.3%, CD 30.5%); few Pts temporarily interrupted treatment (acromegaly 3.7%, CD 10.2%). Conclusions: These data suggest that age, HbA1c, FPG and having prediabetes or diabetes conditions at BL are associated with increased risk of developing pasireotide-induced hyperglycemia. AEs were manageable with antihyperglycemic medication. Potential risk factors associated with pasireotide-induced hyperglycemia may be used to identify Pts who need vigilant monitoring to ensure optimal outcomes during pasireotide treatment.

Presentation: Thursday, June 15, 2023