Hypertension (HTN) and Diabetes (DM) Improvement During Osilodrostat Therapy in Patients with Cushing’s Disease (CD): Analyses from the Phase III LINC 3 study

Friday, May 13, 2022

1:00 PM – 1:15 PM

Location: Station 1, Sapphire West Foyer

Poster Presenter(s)

Alberto M. Pedroncelli, MD, PhD
Head of Clinical Development and Medical Affairs - Endocrinology
Recordati AG
Basel, Switzerland

Submitter(s)

Maria Fleseriu, MD, FACE
Professor, Medicine and Neurological Surgery, Director Pituitary Center
Oregon Health and Science University
Portland, Oregon, United States

Objective : CD is a deleterious hypercortisolism disorder. Alleviating the burden of CD-associated comorbidities, including HTN and DM, is a key treatment goal. Osilodrostat, a potent oral 11β-hydroxylase inhibitor, normalized urinary free cortisol (UFC) and improved clinical signs and symptoms in CD patients (pts) in the Phase III LINC 3 study (NCT02180217). We describe blood pressure (BP) and glucose homeostasis changes in pts with baseline (BL) HTN and DM.

Methods: Adults with CD and mean UFC >1.5 times the upper limit of normal received osilodrostat during the 48-week (W) core study, including an 8W randomized‑withdrawal phase (W26–34) for eligible pts (Pivonello et al. Lancet Diabetes Endocrinol 2020). BL HTN defined as prior diagnosis, taking antihypertensive medication, and/or systolic/diastolic blood pressure (SBP/DBP) >130/ >90 mmHg. BL DM defined as prior diagnosis, taking antidiabetic medication, HbA_1c ≥6.5%, and/or fasting plasma glucose (FPG) ≥126 mg/dL. Exploratory data presented for all pts with data at BL and given visit, unless otherwise stated.

Results: At BL, 87% (119/137) of pts were classed as hypertensive; mean SBP and DBP decreased in these pts during osilodrostat therapy. Of pts with BL SBP >130 mmHg (n=79), 58%, 51% and 49% had SBP ≤130 mmHg at W12, W24 and W48. Of pts with BL DBP >90 mmHg (n=50), 72%, 62% and 66% had DBP ≤90 mmHg at W12, W24 and W48. SBP/DBP remained stable in pts without BL HTN. Higher BL SBP and DBP correlated with greater reductions in these parameters at W24 (SBP, r=−0.57; DBP, r=−0.57 [both P < 0.0001]) and W48 (SBP, r=−0.58; DBP, r=−0.57 [both P < 0.0001]). 40% (34/85) of pts taking antihypertensive medication at BL stopped or reduced the dose by W48; 40% (34/85) increased dose or number of medications. Mean 11-deoxycorticosterone (DOC) increased during the study. Mean p</span>otassium levels remained largely unchanged and did not correlate with DOC increases. 45% (61/137) of pts were classed as diabetic at BL. Of pts with BL FPG ≥100 mg/dL (n=36), 58%, 64% and 44% had FPG < 100 mg/dL by W12, W24 and W48. 49% (21/43) of pts taking antidiabetic medication at BL stopped or reduced the dose by W48; 23% (10/43) increased dose or number of medications. BP or glycemic status change did not correlate with mUFC change from BL.

Discussion/Conclusion: Many CD pts with comorbid HTN or DM had improvements in these parameters during osilodrostat therapy. Close follow-up is needed as concomitant medication adjustments are required in some pts, including those with improvements in HTN or DM. Osilodrostat is effective at improving clinical signs and may alleviate hypercortisolism-associated treatment burden, which could benefit some CD pts.