Lilly Submits NDA/MAA for Tirzepatide, Uses Priority Review Voucher to Accelerate U.S. Launch in Head-to-Head Race Against Semaglutide

On October 26, Eli Lilly announced that it had submitted a New Drug Application (NDA) for tirzepatide to the U.S. FDA and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA), and included a Priority Review Voucher (PRV) with the FDA submission to expedite the market approval of tirzepatide.

Tirzepatide is a novel dual GLP-1R/GIPR agonist administered via once-weekly subcutaneous injection, which integrates the effects of two incretins into a single molecule. GLP-1 (glucagon-like peptide-1) is an "incretin" naturally secreted by the mucosa of the human gastrointestinal tract. It binds to receptors on pancreatic islet cells to stimulate insulin secretion, thereby exerting a glucose-lowering effect. Furthermore, it reduces food intake and delays gastric emptying, which is beneficial for weight management. GIP (glucose-dependent insulinotropic polypeptide) is a hormone that may complement the effects of GLP-1 receptor agonists. Preclinical studies have demonstrated that GIP can reduce body weight by decreasing food intake and increasing energy expenditure. When used in combination with GLP-1 receptor agonists, it may have a greater impact on patients' blood glucose levels and body weight.

The significance of tirzepatide to Eli Lilly is self-evident, as it represents another flagship drug for the company in the diabetes therapeutics market following dulaglutide. From the ambitious program codename “SURPASS” for its pivotal Phase III clinical trials, Eli Lilly demonstrated its resolve to challenge the rival blockbuster semaglutide. The designs of these Phase III trials not only closely mirrored semaglutide’s SUSTAIN program but also included a direct “head-to-head” Phase III trial against semaglutide. Ultimately, the results confirmed that tirzepatide’s efficacy in glycemic control and weight reduction is superior to that of semaglutide.

For Eli Lilly, accelerating the market launch of tirzepatide is a strategic imperative to consolidate its leading position in the antidiabetic drug market. On one hand, Trulicity’s (dulaglutide) market share advantage over Ozempic (semaglutide) is steadily eroding. Meanwhile, semaglutide is enhancing its clinical influence and shaping prescribing decisions through a series of innovative strategic expansions, including an oral formulation and new indications for weight management, Alzheimer’s disease, and NASH. Clearly, relying solely on Trulicity is insufficient to sustain long-term market leadership.

On the other hand, Novo Nordisk is also concurrently developing a dual GLP-1R/GIPR agonist and a combination therapy of semaglutide plus GIPR. Eli Lilly’s rapid market launch of tirzepatide also aims to establish a more solid leading advantage in this new direction.

According to Eli Lilly CEO David Ricks in the Q3 earnings disclosure, tirzepatide is the optimal therapeutic option for diabetes. This clearly reflects Eli Lilly's high expectations for the product, as demonstrated by its willingness to utilize a highly valuable Priority Review Voucher to accelerate the regulatory review process by four months. Under the FDA's priority review procedure and timeline, Eli Lilly anticipates an approximately eight-month period from application submission to market approval, with tirzepatide expected to gain approval by the end of June next year.

The cardiovascular outcomes results for tirzepatide are expected to be announced in 2024, and clinical trials targeting obesity, NASH, and HFpEF are also underway. Additionally, Eli Lilly is developing the oral GLP-1R agonist LY3502970 (Phase II) and the GIPR/GLP-1R/GCGR triple agonist LY3437943 (Phase II).