Slide 1: Medical Treatment of Hypercortisolism with Relacorilant: Final Results of the Phase 3 GRACE Study
Medical Treatment of Hypercortisolism with Relacorilant: Final Results of the Phase 3 GRACE Study Pivonello, Rosario; Arnaldi, Giorgio; Auchus, Richard J.; Badiu, Corin; Busch, Robert; Cannavo, Salvatore; Dischinger, Ulrich; Dobri, Georgiana A.; Donegan, Diane M.; Elenkova, Atanaska; Fazeli, Pouneh
Slide 2: Relacorilant: In Development for the Treatment of Cushing Syndrome
Relacorilant: In Development for the Treatment of Cushing Syndrome ACTH, adrenocorticotropic hormone; AR, androgen receptor; GR, glucocorticoid receptor; MR, mineralocorticoid receptor; PR, progesterone receptor.
Slide 3: The GRACE Phase 3 Study
The GRACE Phase 3 Study Primary endpoints • Loss of hypertension control • Safety Relacorilant Patient population • 18–80 years old • Cushing syndrome Relacorilant Randomization Extension study • Hypertension, hyperglycemia (1:1) (impaired glucose tolerance (optional) or diabetes mellitus), or both
Slide 4: Patient Demographics & Baseline Characteristics
Open Label Patient Demographics & Baseline Characteristics Hypertension & Hypertension only Hyperglycemia only Overall Mean (SD) hyperglycemia (n=31) (n=50) (N=152) (n=71) Age, yrs 43.5 (11.6) 54.1 (13.7) 50.9 (12.6) 50.4 (13.2) Female, n (%) 24 (77.4) 42 (84.0) 61 (85.9) 127 (83.6) Weight, kg 95.2
Slide 5: Open-label Results: Hypertension
Open-label Results HYPERTENSION
Slide 6: Rapid and Sustained Improvements in Blood Pressure by ABPM With Relacorilant
Rapid and Sustained Improvements in Open Label Blood Pressure by ABPM With Relacorilant Patients with hypertension -7.9 -5.1 ABPM, ambulatory blood pressure monitoring; BL, baseline; DBP, diastolic blood pressure; LSM, least squares mean; SBP, systolic blood pressure; SE, standard error. Error bars:
Slide 7: Rapid and Sustained Improvements in Blood Pressure by ABPM With Relacorilant
Rapid and Sustained Improvements in Open Label Blood Pressure by ABPM With Relacorilant Patients with hypertension who took blood pressure medications -7.9 -5.6 ABPM, ambulatory blood pressure monitoring; BL, baseline; DBP, diastolic blood pressure; LSM, least squares mean; SBP, systolic blood press
Slide 8: Rapid and Sustained Improvements in Blood Pressure by ABPM With Relacorilant
Rapid and Sustained Improvements in Open Label Blood Pressure by ABPM With Relacorilant Patients with hypertension who did not take blood pressure medications -3.9 -7.9 ABPM, ambulatory blood pressure monitoring; BL, baseline; DBP, diastolic blood pressure; LSM, least squares mean; ns, not significa
Slide 9: Rapid and Sustained Improvements in Blood Pressure by ABPM With Relacorilant
Rapid and Sustained Improvements in Open Label Blood Pressure by ABPM With Relacorilant Patients with systolic hypertension -4.8 -8.7 ABPM, ambulatory blood pressure monitoring; BL, baseline; DBP, diastolic blood pressure; LSM, least squares mean. SBP, systolic blood pressure; SE, standard error. Er
Slide 10: Rapid and Sustained Improvements in Blood Pressure by ABPM With Relacorilant
Rapid and Sustained Improvements in Open Label Blood Pressure by ABPM With Relacorilant Patients with diastolic hypertension -8.6 -6.1 ABPM, ambulatory blood pressure monitoring; BL, baseline; DBP, diastolic blood pressure; LSM, least squares mean; SBP, systolic blood pressure; SE, standard error. E
Slide 11: Improvements in Day- and Nighttime Blood Pressure by ABPM With Relacorilant
Improvements in Day- and Nighttime Open Label Blood Pressure by ABPM With Relacorilant Patients with hypertension ABPM, ambulatory blood pressure monitoring; BL, baseline; DBP, diastolic blood pressure; LSM, least squares mean; SBP, systolic blood pressure; SE, standard error. Error bars: SE of the
Slide 12: Rapid and Sustained Improvements in Blood Pressure by ABPM With Relacorilant
Rapid and Sustained Improvements in Open Label Blood Pressure by ABPM With Relacorilant Patients with hypertension who met hypertension response criteria & entered the RW phase -12.6 -8.3 ABPM, ambulatory blood pressure monitoring; BL, baseline; DBP, diastolic blood pressure; LSM, least squares mean
Slide 13: Open-label Results: Hyperglycemia
Open-label Results HYPERGLYCEMIA
Slide 14: Rapid and Sustained Improvements in AUC glucose With Relacorilant
Rapid and Sustained Improvements in AUCglucose Open Label With Relacorilant Patients with hyperglycemia (IGT or DM b ) -2.7a aMean change from baseline to visit OL 22: -3.3 h*mmol/L. bDiabetes defined as fasting plasma glucose ≥126 mg/dL, 2-h oGTT plasma glucose ≥200 mg/dL, or HbA1c ≥6.5%. AUCglucos
Slide 15: Rapid and Sustained Improvements in AUC glucose With Relacorilant
Rapid and Sustained Improvements in AUCglucose Open Label With Relacorilant Patients with diabetes (DM) b -3.8a aMean change from baseline to visit OL 22: -4.7 h*mmol/L. bDiabetes defined as fasting plasma glucose ≥126 mg/dL, 2-h oGTT plasma glucose ≥200 mg/dL, or HbA1c ≥6.5%. AUCglucose, glucose ar
Slide 16: Rapid and Sustained Improvements in AUC glucose With Relacorilant
Rapid and Sustained Improvements in AUCglucose Open Label With Relacorilant Patients with hyperglycemia (IGT or DM b ) who met hyperglycemia response criteria & entered the RW phase -6.2a aMean change from baseline to visit OL 22: -6.2 h*mmol/L. bDiabetes defined as fasting plasma glucose ≥126 mg/dL
Slide 17: Greater Improvements in Glucose Parameters in Hyperglycemia Responders
Greater Improvements in Glucose Parameters Open Label With Relacorilant in Hyperglycemia Responders bDiabetes defined as fasting plasma glucose ≥126 mg/dL, 2-h oGTT plasma glucose ≥200 mg/dL, or HbA1c ≥6.5%. BL, baseline; DM, diabetes mellitus; HbA1c, hemoglobin A1c; FPG, fasting plasma glucose; IGT
Slide 18: Open-label Results: Other Symptoms and Comorbidities
Open-label Results OTHER SYMPTOMS AND COMORBIDITIES
Slide 19: Significant Improvements in Body Composition With Relacorilant
Significant Improvements in Body Composition Open Label With Relacorilant BL, baseline; DXA, Dual Energy X-Ray Absorptiometry, OL, open label. Error bars: Standard deviation. Wilcoxon rank sum test P-values for the mean change from baseline shown.
Slide 20: Significant Improvements in Quality of Life and Cognitive Assessments With Relacorilant
Significant Improvements in Quality of Life and Open Label Cognitive Assessments With Relacorilant BL, baseline, OL, open label; QOL, quality of life. Error bars: Standard deviation. Wilcoxon rank sum test P-values for the mean change from baseline shown.
Slide 21: Open-label Results: Safety
Open-label Results “ (ace STUDY
Slide 22: Adverse Event Summary
Open Label Adverse Event Summary Relacorilant n (%) (N=152) • Due to relacorilant’s specificity for the GR Patients reporting at least one TEAE and its unique mechanism of action, the 147 (96.7) (any grade) observed efficacy was seen: Patients reporting at least one grade ≥3 TEAE 37 (24.3) • Without
Slide 23: Adverse Events Occurring in ≥10% of Patients
Open Label Adverse Events Occurring in ≥10% of Patients Among patients in the open-label phase n (%) Relacorilant Nausea 52 (34.2) Edema peripheral 50 (32.9) Pain in extremity 43 (28.3) Back pain 41 (27.0) • The majority of AEs were mild to Fatigue 34 (22.4) moderate in severity Headache 31 (20.4) A
Slide 24: Randomized-withdrawal Results
Randomized-withdrawal Results
Slide 25: Patient Demographics & Baseline Characteristics
Randomized Withdrawal Patient Demographics & Baseline Characteristics 152 Relacorilant Placebo patients enrolled Mean (SD) (n=30) (n=32) Age, yrs 46.6 (11.0) 48.8 (14.4) Female, n (%) 22 (73.3) 26 (81.3) 62.5% (n=95) completed OL phase Weight, kg 93.3 (27.4) 88.6 (21.1) 66.7% (n=44) 57.5% (n=42) BMI
Slide 26: Randomized-withdrawal Results: Hypertension
Randomized-withdrawal Results HYPERTENSION
Slide 27: Primary Endpoint Met: Hypertension
Randomized Withdrawal Primary Endpoint Met: Hypertension Hypertension responders who randomized • In the randomized-withdrawal phase, significantly more patients receiving placebo lost hypertension control compared to those who continued to receive relacorilant • Odds ratio 0.17 for relacorilant vs
Slide 28: Similar Blood Pressure Trends Observed in all Patients Randomized
Randomized Similar Blood Pressure Trends Observed in all Withdrawal Patients Randomized, Favoring Relacorilant Over Placebo In all patients with available ABPM data ABPM, ambulatory blood pressure monitoring; DBP, diastolic blood pressure; ns, not significant (P≥0.05); RW, randomized withdrawal; SBP
Slide 29: Similar Blood Pressure Trends Observed in all Patients Randomized
Randomized Similar Blood Pressure Trends Observed in all Withdrawal Patients Randomized, Favoring Relacorilant Over Placebo In all patients with available ABPM data ABPM, ambulatory blood pressure monitoring; DBP, diastolic blood pressure; ns, not significant (P≥0.05); RW, randomized withdrawal; SBP
Slide 30: Similar Blood Pressure Trends Observed in all Patients Randomized
Randomized Similar Blood Pressure Trends Observed in all Withdrawal Patients Randomized, Favoring Relacorilant Over Placebo In all patients with available ABPM data ABPM, ambulatory blood pressure monitoring; DBP, diastolic blood pressure; ns, not significant (P≥0.05); RW, randomized withdrawal; SBP
Slide 31: Randomized-withdrawal Results: Hyperglycemia and Other Comorbidities
Randomized-withdrawal Results HYPERGLYCEMIA AND OTHER SYMPTOMS AND COMORBIDITIES
Slide 32: Improvements in Glycemic Measures Maintained With Relacorilant
Randomized Improvements in Glycemic Measures Maintained Withdrawal With Relacorilant Relacorilant Placebo (n=30) (n=32) • At the end of the RW phase, patients Change from RW baseline to week RW12 in: who switched to placebo AUCglucose (in patients with hyperglycemia at study entry), h*mmol/L experie
Slide 33: Improvements in Body Composition Maintained With Relacorilant
Randomized Improvements in Body Composition Maintained Withdrawal With Relacorilant Relacorilant Placebo (n=30) (n=32) Change from RW baseline to week RW12 in all patients in the RW phase: Waist circumference n 26 30 Mean (SD), cm -1.2 (3.7) +3.8 (10.4) Wilcoxon signed rank sum P-valuea ns 0.008 Tis
Slide 34: Randomized-withdrawal Results: Safety
Randomized-withdrawal Results SAFETY
Slide 35: Adverse Events Occurring in ≥5% of Patients
Randomized Withdrawal Adverse Events Occurring in ≥5% of Patients Among patients in the randomized-withdrawal phase Relacorilant Placebo n (%) (n=30) (n=32) Back pain 5 (16.7) 6 (18.8) Headache 3 (10.0) 4 (12.5) Arthralgia 3 (10.0) 3 (9.4) Insomnia 0 4 (12.5) Pain in extremity 2 (6.7) 2 (6.3)
Slide 36: Conclusions
Conclusions • GRACE met its primary endpoint • Significant improvements in hypertension, hyperglycemia, and other manifestations of cortisol excess were observed throughout the treatment with relacorilant • Due to relacorilant’s specificity for the glucocorticoid receptor and its unique mechanism of
Slide 37: Thank You!
Thanks to all Those who Contributed to the GRACE Study! The GRACE • Dr. Andjela Drincic • Dr. Honey East • Prof. Dr. Alexandra Kautzky- Willer • • Dr. Pnina Rotman-Pikielny Dr. Sergio Rovner investigators & • Assoc. Prof. Dr. Atanaska Elenkova • Dr. Lawrence Kirschner • Prof. Dr. Adam Kretowski • Dr