FDA Grants Fast Track Designation to Tirzepatide for Obesity, Associated Comorbidities

Tirzepatide received Fast Track designation from the FDA after showing superiority to placebo in treating obesity in clinical trials.

The FDA granted Fast Track designation to tirzepatide, which is being investigated for obese or overweight adults who have weight-related comorbities. Tirzepatide is not indicated for overweight or obese patients with type 2 diabetes.

Tirzepatide is meant to be an addition for patients who are on a reduced-calorie diet and are engaged in greater levels of physical activity.

"We are pleased with the FDA's decision to grant Fast Track designation for tirzepatide, and we look forward to completing our rolling submission next year," said Mike Mason, president, Lilly Diabetes, in a press release.

Obesity impacts nearly 100 million Americans and is a significant driver of health care costs. Although diet and exercise are important factors to decrease excess weight, Mason noted that these do not always provide the results that patients hope for.

Tirzepatide is a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor antagonist. This medication activates the GIP incretin hormone, which blunts metabolic adaptive responses that are often activated through calorie restriction. Combined with the GLP-1 receptor antagonist, it may help to better treat metabolic dysregulation.

GLP-1 and GIP, both of which are classified as incretins, are expressed throughout the body—including pancreatic beta cells and the gastrointestinal tract—and stimulate insulin secretion in a glucose-dependent manner. Incretins are a group of metabolic hormones that are released from the enteroendocrine cells into the bloodstream after eating and stimulate a decrease in blood glucose levels.

The multi-center, randomized, double-blind, parallel, placebo-controlled SURMOUNT-1 trial was the first in the SURMOUNT series, evaluating the safety and efficacy of tirzepatide against the placebo. Co-primary endpoints were superiority of the 10 mg and/or 15 mg dose in reducing bodyweight by 5% or more from baseline to 72 weeks compared to the placebo.

SURMOUNT-1 assessed doses at 5 mg, 10 mg, and 15 mg in 2539obese or overweight individuals without type 2 diabetes. Patients also had at least 1 comorbidity, including hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease.

The trial design of SURMOUNT-2 follows suit with the design of SURMOUNT-1. This second trial only evaluated tirzepatide at 10 mg and 15 mg doses, and the coprimary endpoints were the same as those in SURMOUNT-1.

The FDA grants Fast Track designation to quickly bring promising medicine and treatments to patients by facilitating their development and allowing for faster medical review. Along with the Fast Track designation, a rolling submission could accelerate an FDA approval for tirzepatide.

Currently, researchers are conducting the global phase 3 clinical development program (SURMOUNT-3), enrolling more than 5000 patients in 6 clinical trials. Results are expected to be released in 2023.

“We are dedicated to helping people living with obesity through our research and development of innovative treatments like tirzepatide, which produced significant weight reductions in patients taking tirzepatide for type 2 diabetes in SURPASS. Tirzepatide also helped nearly two-thirds of participants on the highest dose reduce their body weight by at least 20 percent in SURMOUNT-1," Mason said in the press release.

Reference

Lilly. Lilly receives U.S. FDA Fast Track designation for tirzepatide for the treatment of adults with obesity, or overweight with weight-related comorbidities. Lilly Investors. October 6, 2022. Accessed on October 6, 2022. https://investor.lilly.com/news-releases/news-release-details/lilly-receives-us-fda-fast-track-designation-tirzepatide