Lilly Triumphs in First Major Weight-Loss Drug Battle with Superior Tirzepatide Data

On December 4, Eli Lilly and Company announced the topline results of the randomized, open-label Phase 3b clinical trial, SURMOUNT-5. In the study's primary endpoint, tirzepatide (Zepbound®) achieved a 1.47-fold relative weight loss compared to semaglutide (Wegovy®). The study data showed,Tirzepatide achieved an average weight loss of 20.2%, significantly outperforming semaglutide's 13.7%.At Week 72, in non-diabetic overweight adults with obesity or at least one weight-related comorbidity, tirzepatide achieved comprehensive superiority over semaglutide across both the primary endpoint and five key secondary endpoints.

Following the news, Eli Lilly (LLY) surged 2.03% to close at $829.84, with a trading volume of $3.223 billion, ranking 16th among U.S. stocks on the day. The trading volume increased by 42.61% compared to December 3rd. Over the past five trading days, it rose 5.28%, year-to-date it climbed 42.36%, and over the past 52 weeks, it gained 41.09%.

For a long time, SURMOUNT-5 (NCT05822830) has been identified by investors and analysts on Wall Street as one of the most important drug studies this year. The key findings from the trial results could be one of the decisive factors in the share of the over $100 billion annual sales market for drugs between Eli Lilly and Novo Nordisk.

SURMOUNT-5 is a multicenter, randomized, open-label Phase 3b trial designed to evaluate the efficacy and safety of tirzepatide versus semaglutide in adults with obesity or overweight who have at least one comorbidity (such as hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease) but do not have diabetes. The trial enrolled approximately 751 patients from the United States and Puerto Rico and randomly assigned them in a 1:1 ratio to receive either the maximum tolerated dose of tirzepatide (10mg or 15mg) or semaglutide (1.7mg or 2.4mg). The primary objective of the study is to demonstrate the superiority of tirzepatide over semaglutide in terms of percentage reduction in body weight from baseline at Week 72. Secondary endpoints include the proportion of participants in each group achieving specific thresholds (e.g., 10% or 20% weight loss).

According to the trial results currently published by Eli Lilly, Zepbound achieved an average weight loss of 20.2%, while Wegovy achieved an average weight loss of 13.7%. The relative weight loss caused by the former treatment is approximately 47% higher than that of the latter. In other words,Patients treated with Zepbound lost an average of 50 pounds (approximately 45.36 catties), while those on Wegovy lost 33 pounds (approximately 29.94 catties), with the former losing about 17 pounds (15.42 catties) more than the latter.。

In terms of secondary key endpoints, 31.6% of patients in the tirzepatide treatment group achieved a weight loss of at least 25%, compared to only 16.1% in the semaglutide treatment group.

In the SURMOUNT-5 study, the overall safety profile of tirzepatide was similar to that reported in previous SURMOUNT studies. In this study, the most common adverse events for both tirzepatide and semaglutide were mild to moderate gastrointestinal-related adverse events.

Eli Lilly and Company will continue to evaluate the results of the SURMOUNT-5 study and plans to publish them in a peer-reviewed journal and at a medical conference next year. Additionally, in July 2024, a retrospective observational study published in JAMA Internal Medicine showed that tirzepatide has preliminarily demonstrated superior efficacy compared to semaglutide. After six months, tirzepatide led to an average weight loss of 10.1%, while semaglutide resulted in an average weight loss of 5.8%.

Currently, tirzepatide is the only GIP/GLP-1 dual receptor agonist in its class to be approved by the FDA for obesity treatment. Ongoing research is examining its impact on morbidity and mortality (MMO) in patients with chronic kidney disease (CKD) and obesity. This year, Eli Lilly and Company has submitted research data to the U.S. Food and Drug Administration (FDA) and other global regulatory agencies regarding tirzepatide's efficacy in treating obesity with moderate to severe obstructive sleep apnea (OSA). Eli Lilly and Company plans to submit data later this year to the U.S. Food and Drug Administration (FDA) and other global regulatory agencies on tirzepatide's use in treating heart failure with preserved ejection fraction (HFpEF) accompanied by obesity.

In addition, in September 2024, Eli Lilly initiated a Phase 3 clinical trial for weight loss with the small molecule GLP-1 receptor agonist Orforglipron. The enrolled participants were obese patients who completed the SURMOUNT-5 study, targeting broader application scenarios for maintenance therapy following treatment with tirzepatide.

Recently, Novo Nordisk's Wegovy® (semaglutide injection for long-term weight management) has officially been commercially launched in China. It is used for long-term weight management in adult patients based on controlled diet and increased physical activity. The patient's initial Body Mass Index (BMI) should be ≥30kg/m² (obesity) or ≥27kg/m² to <30kg/m² (overweight) with at least one weight-related comorbidity (e.g., hyperglycemia, hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease, etc.).

As the world's first glucagon-like peptide-1 receptor agonist (GLP-1RA) weekly formulation for long-term weight management, Novo Nordisk's Wegovy® has transformed the previous treatment paradigm for obesity, delivering multiple health benefits beyond weight loss. Currently, semaglutide has been approved for marketing in numerous countries worldwide.

Financial reports show that in 2023, the global sales of Semaglutide reached 145.811 billion Danish kroner (approximately 21.615 billion US dollars), increasing by 88.78% year-on-year, accounting for 62.78% of Novo Nordisk's total revenue in 2023. According to Novo Nordisk’s Q3 2024 financial report, the sales of Wegovy increased by 79% year-on-year, reaching 17.3 billion Danish kroner, surpassing analysts' expectations of 15.9 billion Danish kroner.

In the competition with tirzepatide, semaglutide has more than just an early-mover advantage. Obesity is a complex systemic disease associated with more than 200 comorbidities. The clear multiple benefits of semaglutide correspondingly make the treatment of comorbidities and other diseases possible, bringing more opportunities for indication expansion.

In March this year, semaglutide 2.4mg (Wegovy®) received FDA approval for a new indication to reduce the risk of cardiovascular death, non-fatal heart attacks, and non-fatal strokes in adults with cardiovascular disease who are obese or overweight, becoming the first obesity treatment drug approved to reduce the risk of major adverse cardiovascular events (MACE).

This approval is mainly based on the positive results of the SELECT study. This study lasted for five years, covering 41 countries and regions, and included 17,604 patients, making it the largest clinical trial in Novo Nordisk's history. Regarding the primary endpoint of the study, semaglutide 2.4mg reduced the risk of MACE by 20% in adult patients with overweight or obesity who had confirmed cardiovascular disease (CVD) but no history of diabetes.

In the field of Metabolic Dysfunction-Associated Steatohepatitis (MASH), research progress on semaglutide at a dose of 2.4mg has demonstrated its therapeutic potential. The first part of the Phase III ESSENCE study has been successful, confirming its significant efficacy in improving liver fibrosis and inducing the resolution of steatohepatitis.

In the field of chronic kidney disease (CKD), according to the Phase III FLOW trial results published by Novo Nordisk, semaglutide significantly reduced the risk of death in Type 2 diabetes patients with chronic kidney disease (CKD). Novo Nordisk expects to submit an application this year to expand the label of semaglutide to include CKD.

The rapid increase in indications for GLP-1 drugs has made it difficult for production capacity to quickly catch up in the short term. In the fierce competition within the GLP-1 field, while clinical research and development remain the core battleground, capacity planning is also a critical factor that cannot be overlooked. Given the current surge in market demand, expanding production capacity appears to have almost no upper limit. Whoever can seize the initiative in this dimension and continue to push forward will be more likely to stabilize their position and stand out from the competition.

To meet the surging market demand for Tirzepatide, Eli Lilly and Company has implemented a series of bold capacity upgrade strategies. In the United States, Eli Lilly has invested heavily in a complete overhaul of its production base in Indiana, constructing ultra-modern biopharmaceutical facilities and introducing world-class fermentation and purification equipment to precisely control every step of the production process, aiming to push drug manufacturing efficiency to new heights. Moreover, Eli Lilly is actively deepening collaborations with international supply chain partners, securing high-quality raw material suppliers through long-term stable supply contracts, laying a solid foundation for capacity expansion from the source while striving to eliminate risks of supply chain disruptions.

In May this year, Eli Lilly and Company announced the largest capacity investment in the company's 150-year history — an additional $5.3 billion, bringing the total investment to $9 billion for expanding production to increase the output of tirzepatide. In China, Eli Lilly and Company also announced an investment of approximately 1.5 billion RMB to upgrade the production capacity of its Suzhou plant, aiming to expand the production scale of tirzepatide.

Novo Nordisk, which already has five strategic production bases globally located in Denmark, the United States, France, Brazil, and China, employs nearly 20,000 workers in its production department. Since the first approval of semaglutide for marketing in 2017, Novo Nordisk has been expanding its production capacity, marking the beginning of a well-planned long-term upgrade. In 2024, Novo Nordisk plans to increase investment on top of the current level, aiming to allocate $6.8 billion to the production sector, significantly higher than the previous year's investment of $3.9 billion.

Since the beginning of this year, in order to further address capacity issues, Novo Nordisk has taken frequent actions to continue expanding the production capacity of semaglutide. At the start of the year, Novo Nordisk announced the acquisition of three Catalent manufacturing facilities for $11 billion; mid-year, it also announced plans to invest $4.1 billion to build a second fill/finish manufacturing facility in Clayton, North Carolina, to enhance the company's ability to produce injectable treatments for obesity and other serious chronic diseases both now and in the future. In China, Novo Nordisk announced an investment of approximately 4 billion RMB for the expansion of sterile formulation production at its pharmaceutical base in Tianjin Economic-Development Area (TEDA), Binhai New Area, to further increase its production capacity in the Chinese market.

On December 4, the day the topline results of the head-to-head SURMOUNT-5 study of semaglutide and tirzepatide were announced, Novavax announced the sale of a recombinant protein manufacturing plant located in the Czech Republic to Novo Nordisk for $200 million.