Slide 1: Efficacy and Safety of Avexitide for Treatment of Hypoglycemia after Gastrointestinal Surgery
Efficacy and Safety of Avexitide for Treatment of Hypoglycemia after Gastrointestinal Surgery; Assessment of Novel Dosing Regimens in an Expanded Indication Marilyn Tan, MD, FACE Clinical Associate Professor | Department of Medicine | Division of Endocrinology | Stanford University School of Medicin
Slide 2: Presenter Disclosures
Presenter Disclosures I have received research support from Eiger BioPharmaceuticals, Inc. as a site investigator. This study is an investigator-initiated trial with funding provided by Eiger BioPharmaceuticals, Inc. 2
Slide 3: Post-Bariatric Hypoglycemia (PBH)
Post-Bariatric Hypoglycemia (PBH) A COMPLICATION OF GASTROINTESTINAL SURGERY • 29-34% after Roux-en-Y gastric bypass (RYGB)1,2,3,4 • 11%–23% after vertical sleeve gastrectomy (VSG)1,2,3,4,5; also reported after other GI surgeries Glucose (mg/mL) • Postprandial hypoglycemia 1-3 hours after meals • Ne
Slide 4: Therapeutic Approach to PBH
Therapeutic Approach to PBH NO APPROVED TREATMENTS; HIGH UNMET MEDICAL NEED • Medical nutrition therapy - Frequent small meals/CHO restriction/low glycemic index • Stepped pharmacotherapy follows (off-label use) - Acarbose Octreotide Diazoxide SAFE, EFFECTIVE, AND TARGETED - Limited by efficacy/
Slide 5: Pathophysiology: Exaggerated Secretion of GLP-1
Pathophysiology: Exaggerated Secretion of GLP-1 CAUSING SYMPTOMATIC HYPERINSULINEMIC HYPOGLYCEMIA Avexitide (exendin 9-39) GLP-1r Blockade 5 Craig et al. Diabetes, Obes and Metab. 2018;20(2):352-361.
Slide 6: GLP-1 Receptor Antagonism: A Targeted Therapeutic Approach to PBH
GLP-1 Receptor Antagonism: A Targeted Therapeutic Approach to PBH PROOF OF CONCEPT STUDY DEMONSTRATED PREVENTION OF HYPERINSULINEMIC HYPOGLYCEMIA N=8 N=8 Avexitide Infusion Avexitide Avexitide • 100% prevention of hypoglycemia • Increased the plasma glucose nadir by Insulin (μU/ml) Glucose (mg/dL) 7
Slide 7: Prior Avexitide Trials
Prior Avexitide Trials SAFE AND EFFECTIVE PREVENTION OF HYPERINSULINEMIC HYPOGLYCEMIA IN PATIENTS WITH PBH Study # of Patients Dosing/Duration Status IV Infusion 8 Single dose Published in Diabetologia SubQ Injection – SAD 8 Single dose Presented at ADA 2016 | Published in Diabetes, Obesity and Meta
Slide 8: Avexitide for Hypoglycemia after GI Surgery
Avexitide for Hypoglycemia after GI Surgery DOSE EXPLORATION IN AN EXPANDED PATIENT POPULATION1 N=8 N=8 Primary efficacy endpoint Rate of daytime Level 2 hypoglycemia by CGM (glucose <54 mg/dL) 1Enrollment Population: RYGB, VSG, esophagectomy, gastrectomy, Nissen fundoplication patients with severe,
Slide 9: Participant Characteristics
Participant Characteristics 16 PARTICIPANTS WITH SEVERE HH AFTER RYGB, VSG, GASTRECTOMY, NISSEN FUNDOPLICATION Characteristic Total (N=16*) Demographic / Anthropomorphic Characteristic Sex, female/male, n (%) 14/2 (87.5/12.5) Age, mean (SD), years 47.8 (12.8) Weight, mean (SD), kg 79.4 (14.8) BMI, m
Slide 10: Significant Reductions in Hypoglycemia Events by SMBG / eDiary
Significant Reductions in Hypoglycemia Events by SMBG / eDiary CONSISTENT IMPROVEMENTS OBSERVED WITH BOTH DOSING REGIMENS Treatment Period (n=16) Parameter Avexitide Avexitide Measured by Baseline 45 mg BID 90 mg QD eDiary and SMBG % Decrease Mean Event % Decrease Mean (SD) Mean (SD) p-value p-value
Slide 11: Significant Reductions in Hypoglycemia with Avexitide
Significant Reductions in Hypoglycemia with Avexitide % TIME IN HYPOGLYCEMIA AND # OF HYPOGLYCEMIA EVENTS AS MEASURED BY BLINDED CGM % Time in Hypoglycemia1 35 # of Hypoglycemia Events 20 # of Diurnal3 Hypoglycemia Events 4.5% in 14 Days2 in 14 Days 4.0% 30 3.5% 31% 25% 20% ** 51% 25 * 15 3.0% 47% 4
Slide 12: Significant Reductions in % Time in Hypoglycemia by CGM
Significant Reductions in % Time in Hypoglycemia by CGM AMPLIFICATION OF EFFECT FOR POST-GASTRECTOMY PATIENTS % Time <70 mg/dL % Time <54 mg/dL % Time <40 mg/dL 5% 3.5% 1.6% 3.0% 1.4% 4% 2.5% 1.2% 3% 1.0% 2.0% 0.8% 2% 1.5% 0.6% 1.0% 0.4% 1% 0.5% 0.2% 0% 0.0% 0.0% RYGB VSG Gastrectomy RYGB VSG Gastre
Slide 13: Avexitide Safety
Avexitide Safety AVEXITIDE WAS WELL-TOLERATED WITH NO SAFETY SIGNALS IDENTIFIED • No SAEs • Most common AEs: diarrhea, headache, bloating, and injection site reaction / bruising • AEs were mild to moderate in severity and transient • All AEs were self-limited and resolved without treatment • No part
Slide 14: Conclusions
Conclusions EFFICACY AND SAFETY SUPPORT NOVEL DOSING REGIMEN IN AN EXPANDED INDICATION • Avexitide (exendin 9-39) is a first-in-class GLP-1 receptor antagonist in development for treatment of PBH and other forms of HH, including congenital hyperinsulinism • 28 days of treatment in patients with HH a
Slide 15: Acknowledgements
Acknowledgements AVEXITIDE STUDY TEAM STUDY PARTICIPANTS Termeh Shamloo “My husband noted I’m in a much better mood, and my nocturnal hypoglycemia was all gone.” Stanford University School of Medicine “Experience was amazing…” Dalia Perelman, RD Stanford University School of Medicine "I felt great a