Leonard Glass, Vice President, Global Medical Affairs at Eli Lilly & Co. Shares Insights from Lilly’s Vision on New Stage of Metabolic Science

Shots:

Leonard spoke about how Lilly is advancing in the field of metabolic disease research (esp. diabetes)
He also talked about its lead candidate in type 2 diabetes and also discussed its clinical results in detail
The interview summarizes Lilly’s objective to advance new discoveries and redefine diabetes care

Smriti: Tell us how Lilly is leading in the market through its metabolic disease research? Tell us more about its efforts to remain the leader in the metabolic diseases

Leonard Glass: Lilly has been a global leader in diabetes care for over 100 years and over the last few years, we have refined our focus for people living with metabolic diseases, like diabetes and obesity.

Lilly scientists harness the power of biotechnology to urgently advance new discoveries with the potential to radically transform care across metabolic diseases. We invest more of Lilly’s revenues in R&D than nearly any other company in our industry. We’re simplifying disease management by developing personalized digital tools for people with diabetes and migraine, and applying cutting-edge technologies to bring more discoveries to patients, including the world’s first fully automated lab that accelerates the discovery of new medicines.

Smriti: Shed some light on the lead candidate, Mounjaro (its MOA, ROA, formulation, pathway, etc.)

Leonard Glass: Mounjaro is the first and only, once-weekly GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist approved by the U.S. Food and Drug Administration (FDA) as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.

“Mounjaro is a single molecule that activates the body’s receptors for GIP and GLP-1, which are natural incretin hormones released by the body in response to nutrients to regulate glucose metabolism. The release of GIP and GLP-1 in response to food intake to regulate blood glucose is known as the incretin effect, which is diminished in people with type 2 diabetes. In addition, GIP is responsible for the majority of the incretin effect.”

A phase 1 mechanism of action study showed that Mounjaro improved glycemic control through improvements in two of the major areas of impairment in type 2 diabetes: increased insulin sensitivity and reduced glucagon secretion.

Smriti: Can you brief us about the US FDA approval of Mounjaro?

Leonard Glass: The U.S. Food and Drug Administration approved Mounjaro™ (tirzepatide) injection on May 13, 2022. Mounjaro is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.

Mounjaro is the first and only FDA-approved GIP and GLP-1 receptor agonist, representing the first new class of medicines introduced for adults with type 2 diabetes in nearly a decade. The FDA approval is based on data from the phase 3 SURPASS program, which evaluated the efficacy and safety of Mounjaro.

Tirzepatide is also under regulatory review for the treatment of type 2 diabetes in Europe, Japan and several additional countries.

Smriti: Discuss some points on the clinical results of Mounjaro?

Leonard Glass: The phase 3 SURPASS program evaluated the efficacy and safety of Mounjaro in a broad spectrum of adults with diabetes. These studies ranged from 40 to 52 weeks and evaluated the efficacy and safety of Mounjaro 5 mg, 10 mg and 15 mg as a monotherapy and as an add-on to various standard-of-care medications for type 2 diabetes. The active comparators in the studies were injectable semaglutide 1 mg, insulin glargine and insulin degludec.

Across the program, Mounjaro consistently delivered superior A1C reductions in adults with type 2 diabetes compared to placebo and all active comparators. While not indicated for weight loss, Mounjaro also delivered significant weight reductions across the phase 3 program as a key secondary endpoint.

Additionally, the studies evaluated a diverse range of people with diabetes, representing adults who had type 2 diabetes for only five years to more than 13 years on average. The most common side effects reported in at least 5% of patients treated with Mounjaro included nausea, diarrhea, decreased appetite, vomiting, constipation, indigestion (dyspepsia), and stomach (abdominal) pain.

Smriti: Tell us how Mounjaro will lead in the competition?

Leonard Glass: Mounjaro represents the first in a new class of medicines introduced to treat type 2 diabetes in nearly a decade. Mounjaro is the first and only GIP and GLP-1 receptor agonist approved by the FDA to treat type 2 diabetes. It is a single molecule that activates the body’s receptors for GIP and GLP-1, two natural incretin hormones. Currently available incretins activate only the body’s receptors for GLP-1.

In a head-to-head clinical trial, all three doses of Mounjaro studied were proven to deliver superior A1C and significant body weight reductions compared to injectable semaglutide 1 mg. Mounjaro reduced A1C by between 2% (5 mg) and 2.3% (15 mg), compared to 1.9% for semaglutide.

Smriti: Are there any other indications where Mounjaro is being assessed?

Leonard Glass: Tirzepatide is in phase 3 development for the treatment of obesity or overweight, and heart failure with preserved ejection fraction (HFpEF) in people with obesity. It is also being studied as a potential treatment for non-alcoholic steatohepatitis (NASH). Studies of tirzepatide in obstructive sleep apnea (OSA) and its effects on morbidity/mortality in obesity are planned as well. These trials are ongoing, and we look forward to sharing additional results as they become available.

Additionally, SURPASS-CVOT, our phase 3 cardiovascular outcomes trial assessing both non-inferiority and superiority of tirzepatide in a head-to-head trial against Trulicity 1.5 mg, is ongoing. The SURPASS-CVOT trial design, evaluates tirzepatide against a therapy proven to significantly reduce the risk of major adverse cardiovascular events. This event-driven trial is expected to be completed in 2024.

We have also recently initiated SURPASS-PEDS, which will evaluate the efficacy and safety of tirzepatide compared to placebo in children or teenagers between ages 10 and 18 with type 2 diabetes taking metformin, basal insulin or both.

Smriti: What are your plans in the metabolic diseases space? (Indications, molecules in pipeline)

Leonard Glass: Lilly continues to invest in internal R&D and new technologies to quickly bring more discoveries to patients. Lilly is urgently advancing new discoveries that have the potential to radically transform diabetes care, advance immunology, turn hard-to-treat cancers from fatal to manageable, and save lives by treating COVID-19. We’re also committed to discovering treatments for hard-to-treat diseases like Alzheimer’s.

Source: Canva

About the Author:

Leonard Glass, M.D., F.A.C.E. is Vice president of global medical affairs at Eli Lilly and Company, where he oversees the flow of scientific information and clinical expertise between Lilly Diabetes and the medical community. He is an endocrinologist with a special interest in physiology, insulin resistance syndrome, and type 1 and type 2 diabetes. Leonard earned his Bachelor of Science in biology from the University of Miami and his Doctor of Medicine from Eastern Virginia Medical School. He completed his internal medicine residency and clinical research fellowship in endocrinology, diabetes, and metabolism at the University of Texas Health Science Center in San Antonio. Leonard is also a Fellow of the American Association of Clinical Endocrinology (FACE)