Glucagon-Blocking Drug Reduces Need for Insulin and Improves Blood Glucose Levels for Patients with Type 1 Diabetes

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Jun 13, 2017, 14:45 ET

SAN DIEGO, June 13, 2017 /PRNewswire-USNewswire/ -- A single dose of the glucagon-blocking drug REMD-477 can substantially reduce the amount of insulin needed and improve glucose levels without increasing hypoglycemia (low blood glucose levels) in patients with type 1 diabetes, according to the study, "REMD-477, a Human Glucagon Receptor (GCGR) Antibody, Reduces Daily Insulin Requirements and Improves Glycemic Control in People with Type 1 Diabetes (T1D)," presented today at the American Diabetes Association's 77th Scientific Sessions® at the San Diego Convention Center in San Diego. Glucagon is a hormone produced by the pancreas that raises blood glucose and works together with insulin, which has the opposite effect, to tightly regulate blood glucose concentrations. In individuals with diabetes, glucagon effects may not be appropriately balanced by insulin, resulting in elevated blood glucose.

The double-blind, randomized, placebo-controlled study enrolled 21 adult patients (8 men and 13 women) with T1D. Prior to being admitted for a five-day, in-patient observation period, all participants' glucose levels were measured by Continuous Glucose Monitoring (CGM). While under observation, all patients received the same meals and a continuous IV insulin infusion to help maintain glucose levels.

On the second day of observation, 10 patients received a single 70 milligram (mg) subcutaneous injection of the glucagon-blocking drug, REMD-477—a fully human antibody that specifically binds to and blocks glucagon receptor signaling for the treatment of metabolic disorders, including T1D. The remaining 11 patients received a placebo injection. (REMD-477 was discovered with Xenomouse technology, which recapitulates a human antibody response in the mouse, and the antibody sequences are fully human.)

Daily insulin use and glucose levels of patients who received REMD-477 were compared on day one versus day four of observation to those who received placebo. Results indicated that those who received the REMD-477 treatment were able to reduce daily insulin use by 26 percent (12 units), compared to those who received the placebo (p=0.02).

Participants received CGM for 8 weeks after inpatient observation. Average daily glucose assessed by CGM was 20 to 31 mg/dL lower in the REMD-477 patients than in the placebo patients during the 3 weekly periods after inpatient observation (p<0.05). In addition, the REMD-477 patients' blood glucose levels were improved without increasing low blood glucose events. Given the long-acting nature and persistent blood concentrations of REMD-477, it is likely that patients may be dosed once per week.

"Our study strongly supports the long-held theory that blocking glucagon may have a significant clinical impact on care for people with type 1 diabetes by improving glucose levels and lowering insulin doses," said Jeremy Pettus, MD, assistant professor of medicine in the endocrinology department at the University of California, San Diego. "We expected that the drug [REMD-477] would have an effect, yet the degree to which the drug reduced the need for insulin and improved patients' blood sugar levels without increasing hypoglycemia events was a surprise."

This study measured the effect of the glucagon-blocking drug after only one injection. The follow-up study will focus on treating more patients over a longer period of time and will compare weekly injections of two different dose strengths. The results of the follow-up study should provide a more complete picture of how REMD-477 may affect patients' blood glucose levels, insulin use and weight in an outpatient setting.

To speak with Dr. Pettus, please contact the Association's media relations team on-site at the San Diego Convention Center on June 9-13 by phone at 619-525-6250 or by email at [email protected].

The American Diabetes Association's 77th Scientific Sessions, to be held June 9-13, 2017, at the San Diego Convention Center, is the world's largest scientific meeting focused on diabetes research, prevention and care. During the five-day meeting, health care professionals have exclusive access to more than 2,500 original research presentations, participate in provocative and engaging exchanges with leading diabetes experts, and can earn Continuing Medical Education (CME) or Continuing Education (CE) credits for educational sessions. The program is grouped into eight interest areas: Acute and Chronic Complications; Behavioral Medicine, Clinical Nutrition, Education and Exercise; Clinical Diabetes/Therapeutics; Epidemiology/Genetics; Immunology/Transplantation; Insulin Action/Molecular Metabolism; Integrated Physiology/Obesity; and Islet Biology/Insulin Secretion. Brenda Montgomery, RN, MSHS, CDE, President of Health Care and Education^[1], will deliver her address on Saturday, June 10, and Alvin C. Powers, MD, President of Medicine and Science, will present his address on Sunday, June 11. Eight abstracts were selected by the Scientific Sessions Meeting Planning Committee to be presented on Tuesday, June 13, in the President's Oral Session. These abstracts represent important research being conducted in the field of diabetes today. In total, the 2017 Scientific Sessions includes 378 abstracts in 49 oral sessions; 2,152 poster presentations including 50 moderated poster discussions; and 360 published-only abstracts. Join the Scientific Sessions conversation on Twitter, #2017ADA.

About the American Diabetes Association
More than 29 million Americans have diabetes, and every 23 seconds another person is diagnosed with diabetes. The American Diabetes Association (Association) is the global authority on diabetes and since 1940 has been committed to its mission to prevent and cure diabetes and to improve the lives of all people affected by diabetes. To tackle this global public health crisis, the Association drives discovery in research to treat, manage and prevent all types of diabetes, as well as to search for cures; raises voice to the urgency of the diabetes epidemic; and provides support and advocacy for people living with diabetes, those at risk of developing diabetes and the health care professionals who serve them. For more information, please call the American Diabetes Association at 1-800-DIABETES (1-800-342-2383) or visit diabetes.org. Information from both of these sources is available in English and Spanish. Find us on Facebook (American Diabetes Association), Twitter (@AmDiabetesAssn) and Instagram (@AmDiabetesAssn).

378-OR REMD-477, a Human Glucagon Receptor (GCGR) Antibody, Reduces Daily Insulin Requirements and Improves Glycemic Control in People with Type 1 Diabetes (T1D)

77th Scientific Sessions
News Briefing: Novel Therapies, Monday, June 12, 2017, 1:15 p.m. PT

Oral Presentation: ADA Presidents Oral Session
Location: Ballroom 20C
Session Time: Tuesday, June 13, 2017, 9:45 a.m. - 11:45 a.m.

Authors: JEREMY PETTUS, DOMINIC REEDS, TRICIA SANTOS CAVAIOLA, SCHAFER BOEDER, MICHELLE LEVIN, EDDA CAVA, DUNG THAI, JIM SHI, HAI YAN, EDGAR BAUTISTA, JOHN MCMILLAN, ROBERT R. HENRY, SAMUEL KLEIN, La Jolla, CA, St. Louis, MO, San Diego, CA, Camarillo, CA, Del Mar, CA

Studies conducted in rodent models of T1D have shown that glucagon receptor blockade normalizes plasma glucose concentration without the need for exogenous insulin. We conducted a randomized, double-blind, placebo (PBO) controlled trial in 21 subjects with T1D (8 men,13 women) to evaluate the effect of a single 70 mg SC injection of REMD-477, a human monoclonal antibody against the GCGR, on daily insulin requirements and glycemic control. After obtaining baseline insulin use and data from Continuous Glucose Monitoring (CGM), subjects were admitted to the Clinical Research Unit for 5 days. Insulin was provided by continuous IV infusion to maintain postabsorptive and postprandial plasma glucose between 90-120 mg/dl and <180 mg/dl, respectively. Standard meals were provided to ensure the same daily energy and macronutrient contents were consumed during the inpatient study. Drug/PBO was given on the second day of admission. The primary endpoint was the comparison between groups in the change in daily insulin requirements on day 4 from day 1. An interim analysis of the first 17 subjects found REMD-477 treatment reduced daily insulin use by 32% (4.2%, 60%) vs. PBO on Day 4 (p=0.027). Average daily glucose assessed by CGM was 19 mg/dL (6.2, 31; p=0.006), and 26 mg/dL (8.2, 45; p=0.008) lower in the REMD-477 group than in the PBO group at Weeks 2 and 3 after treatment, respectively. Glucose time-in-range (70-180 mg/dL) for REMD-477 was 9.5% (2.7%, 16%; p=0.009) and 13% (1.9%, 25%; 0=0.026) greater in the REMD-477 group than in the PBO group during Weeks 2 and 3 after treatment, respectively. REMD-477 therapy was well tolerated and no episodes of severe hypoglycemia were noted. These data demonstrate that a single SC injection of REMD-477 reduces daily insulin requirements while simultaneously improving glucose control, as measured by average glucose concentration and glucose time-in-range, without increasing hypoglycemia in subjects with T1D.

Author Disclosures: J. Pettus: Consultant; Author; Sanofi, Novo Nordisk Inc., Valeritas, Inc., Insulet Corporation, MannKind Corporation, Senseonics, Dexcom, Inc.. Speaker's Bureau; Author; Sanofi, Valeritas, Inc.. D. Reeds: None. T. Santos Cavaiola: None. S. Boeder: None. M. Levin: None. E. Cava: None. D. Thai: Employee; Author; REMD Biotherapeutics. Stock/Shareholder; Author; REMD Biotherapeutics. J. Shi: Stock/Shareholder; Author; REMD Biotherapeutics. H. Yan: Board Member; Author; REMD Biotherapeutics. Employee; Author; REMD Biotherapeutics. Stock/Shareholder; Author; REMD Biotherapeutics. E. Bautista: Stock/Shareholder; Author; REMD Biotherapeutics. J. McMillan: None. R.R. Henry: Advisory Panel; Author; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Sanofi. Consultant; Author; Alere, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc., Ionis Pharmaceuticals, Janssen Pharmaceuticals, Inc., REMD Biotherapeutics, Sanofi. Research Support; Author; AstraReal, Eli Lilly and Company, Hitachi, Ltd., Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc., ViaCyte, Inc. S. Klein: None.

^[1] Disclosures for Brenda Montgomery. Employer: AstraZeneca Pharmaceuticals. Montgomery's role as President, Health Care & Education of the American Diabetes Association (Association) is a voluntary position to which she was elected by the members of the Association in 2015. She continues to recuse herself from any and all discussions, decisions or votes that have or could be perceived as having a conflict of interest with her employer.

SOURCE American Diabetes Association