1004-P: Oral Insulin (ORMD-0801) Effects on Glucose Parameters in Uncontrolled T2DM on OADs

Abstract

ORMD-0801 is a novel oral human insulin formulation which can potentially improve acceptance and adherence, as well as glycemic control by increasing hepatic insulin exposure, without increasing hypoglycemia risk. This randomized, placebo-controlled, multi-center, phase 2b 12-week study, in 273 T2DM subjects, on metformin ±1-2 oral antidiabetic drugs (OADs), including sulfonylurea, compared placebo vs. 32 mg ORMD-0801 capsules administered once daily (QD) at bedtime, or two (BID) or three (TID) times daily at bedtime, and 30-40 min before breakfast/lunch. Blinded continuous glucose monitoring (CGM) was performed during a two-week run-in period and over the last two weeks of treatment. HbA1c levels improved from baseline for all active treatment regimens (Table). Glucose AUC improved from baseline following QD and BID treatment. Hypoglycemia rates were low and relatively similar to the placebo arm, and body weight was unchanged in all treatment arms. Frequency of drug-related adverse events was similar across treatment groups. In conclusion, ORMD-0801 elicited clinically significant HbA1c reductions among T2DM patients inadequately controlled on standard therapies, without increasing hypoglycemia rates, or inducing severe or serious adverse effects or significant weight gain. Disclosure R. Eldor: Advisory Panel; Self; Oramed. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Medtronic, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. Stock/Shareholder; Self; Oramed. G. Fleming: Consultant; Self; ADOCIA, Biocon, Caladrius Biosciences, Inc., Dance Biopharm Holdings, Inc., Diasome Pharmaceuticals, Inc., Intarcia Therapeutics, MannKind Corporation, NuSirt Biopharma, Inc., Oramed Pharmaceuticals, Sanofi, Tolerion, Inc. J. Neutel: None. K.E. Homer: None. M. Kidron: Employee; Self; Oramed Pharmaceuticals. Stock/Shareholder; Self; Oramed Pharmaceuticals. J. Rosenstock: Research Support; Self; AstraZeneca, Bristol-Myers Squibb, Genentech, Inc., GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Oramed Pharmaceuticals, PegBio Co., Ltd., Pfizer Inc., REMD Biotherapeutics. Other Relationship; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi.