On Wednesday, November 8, US Eastern Time, the US Food and Drug Administration (FDA) announced that Eli Lilly's injection with the trade name of Zepbound (Tirzepatide) was approved for the long-term weight management of adults who are obese (with a BMI of 30 or higher) or overweight (with a BMI of 27 or higher) and have at least one weight related disease (such as hypertension, type II diabetes or high cholesterol).
Lilly claims that Zepbound injection is the first and only obesity treatment drug that can activate GIP (glucose dependent insulin stimulating peptide) and GLP-1 (glucagon like peptide-1) hormone receptors. The principle is to reduce patients' appetite and food intake by taking the drug, directly targeting the root cause of overweight.
Zepbound has six dosage forms with a list price of $1059.87 (approximately RMB 7721.47), which is about 20% lower than the selling price of Novo Nordisk's weight loss drug Wegovy. Lilly expects to launch the drug in the US market by the end of this year.
In May last year, FDA approved Tilpodide injection to improve the blood sugar control of adult patients with type 2 diabetes. The product is called Mounjaro. This year, the weight loss indication of the drug was approved. This also means that Lilly will directly compete with the Novo Nordisk Chamber in the field of weight loss.
72 weeks average weight loss exceeding 40 pounds
Lilly's Zepbound's SURMOUNT Phase 3 global clinical development program for chronic weight management was launched at the end of 2019 and has recruited over 5000 obese or overweight patients in six registered studies, four of which are global studies.
The FDA's approval is based on the results of Phase 3 trials of SURMOUNT-1 and SURMOUNT-2. According to Lilly's official website, SURBOUNT-1 is a study of 2539 adults suffering from obesity or overweight and weight related health problems (excluding diabetes). The patients taking Zepbound as a dietary and exercise aid had significantly reduced body weight at 72 weeks compared with placebo. At the highest dose (15 milligrams), people taking Zepbound lost an average of 48 pounds (approximately 43.54 pounds), while at the lowest dose (5 milligrams), people lost an average of 34 pounds (30.84 pounds). In contrast, people taking placebo lost 7 pounds (approximately 6.35 pounds).
In addition, one-third of patients taking the highest dose of Zepbound lost more than 58 pounds (25% of their weight, approximately 52.62 pounds), while those taking placebo lost 1.5% of their weight. The average starting weight is 231 pounds (approximately 209.6 pounds).
The SURBOUNT-2 study on obese or overweight patients with type 2 diabetes showed that Zepboundd (10mg and 15mg) achieved better weight loss than placebo at 72 weeks of treatment. Compared to placebo, this study met both the common primary endpoint and all key secondary endpoints. Compared with placebo (3.3%, 3.2kg), the 10mg group had an average weight loss of 13.4% (13.5kg), while the 15mg group had an average weight loss of 15.7% (15.6kg).
In addition, 81.6% and 86.4% of patients in the 10mg and 15mg groups lost more than 5% of their weight, respectively, while the proportion in the placebo group was 30.5%, achieving a common primary endpoint. Zepbound also achieved all key secondary endpoints, including a reduction in A1C (glycated hemoglobin) and other cardiac metabolic parameters. Compared with placebo, the A1C decrease was similar to the SURPASS test in adults with type 2 diabetes.
In addition, Lilly has also submitted a weight loss indication listing application for Zepbound in China, which is currently under review.
The official website of Lilly also mentioned that although it has not been approved for the treatment of these diseases, in a clinical trial, changes in cholesterol, as well as reductions in blood pressure and waist circumference were observed in individuals who were treated for obesity, overweight, and weight related medical problems through diet, exercise, and Zepbound.
However, it is worth noting that using Zepbound may cause gastrointestinal adverse reactions, sometimes even severe. The most common adverse events (observed in ≥ 5% of clinical trial participants) are nausea, diarrhea, vomiting, constipation, abdominal pain, indigestion, injection site reactions, fatigue, allergic reactions, belching, hair loss, and gastroesophageal reflux disease.
In studies, most nausea, diarrhea, and vomiting occur when people increase dosage, but the effect usually weakens over time. In addition, Zepbound's label contains a black box warning about thyroid C-cell tumors. Patients with a personal or family history of medullary thyroid cancer, type 2 multiple endocrine tumor syndrome, and patients known to have severe allergies to any excipients in Zepbound are contraindicated.
The "Two Strong Fighters" in the Field of Weight Loss
In March 2023, the World Obesity Alliance released the 2023 World Obesity Map, which estimated global overweight or obesity (BMI ≥ 25 kg/m2) data indicating that at age> Among the 5-year-old population, the global number of obese or overweight people in 2020 was 2.6 billion, and by 2035, this number is expected to exceed 4 billion, from 38% in 2020 to over 50% by 2035. It is expected that by 2035, the prevalence of obesity (BMI ≥ 30 kg/m2) will increase from 14% in 2020 to 24% in 2035, and the number of people will reach nearly 2 billion. This means that the future market for weight reduction is very broad.
At present, the targets of weight loss drugs mainly involve glucagon like peptide-1 receptor (GLP-1R), insulin stimulating peptide receptor (GIPR), human glucagon receptor (GCGR), and fibroblast growth factor 21 (FGF21), among which GLP-1R is the mainstream research and development target of weight loss drugs.
Lilly's Zepbound is a GIP/GLP-1 receptor dual agonist that can activate both GLP-1 receptor and GIP receptor mediated signaling pathways to achieve weight loss through multiple mechanisms.
Both GIP and GLP-1 belong to the category of intestinal proinsulin. GIP acts on bone and adipose tissue, inhibiting bone resorption and promoting lipid synthesis in adipocytes, thereby affecting lipid metabolism and fat distribution; GLP-1 mainly reduces food intake through central appetite inhibition. Currently, it is believed that the combination of GLP-1 and GIP is a potential therapeutic strategy.
However, the polypeptide weight-loss drug Saxenda and Wegovy belonging to Novo Nordisk, which were previously approved by FDA for marketing, belong to GLP-1 receptor agonists. Their mechanism of action is to simulate the effect of GLP-1, increase insulin secretion, and control the blood sugar concentration of diabetes patients.
Among them, Smeglutide was approved by the United States in June 2021 and submitted a listing application in China in June 2023. At present, Liraglutide, a biologically similar drug from East China Medicine, and Benarutide from Renhui Biology were also approved for weight loss indications in July 2023.
In 2023, Wegovy& Reg; (Smeglutide Injection) achieved revenue of DKK 21.729 billion (approximately $3.125 billion) in the first three quarters, a year-on-year increase of 492%, and revenue of DKK 9.648 billion (approximately $1.387 billion) in the third quarter alone.
Last May, Lilly's Tilposide showed a momentum of "coming from behind" after being listed for hypoglycemic indications. Guojin Securities stated that Mounjaro& Reg; Since its launch, the growth rate of prescription volume has far exceeded the same level as the weekly formulations of Dulaglutide and Smeglutide.
As of October 20, 2023, the weekly volume of Tilposide is close to 250000. In the first three quarters of 2023, global sales of Tilposide reached 2.958 billion US dollars, of which global sales in the third quarter were 1.409 billion US dollars; Tilposide achieved a single quarter sales breakthrough of $1 billion in the sixth quarter after its launch, and its prescription share in the GLP-1 drug market in the United States has risen to 19.5%.
Although Lilly's Tirzepatide has just expanded its weight loss indications, it was mentioned in a report by the Associated Press that due to Wegovy's supply limitations, some Americans have previously used Tirzepatide for weight loss. By the end of this year, after Lilly's Zepbound is launched into the market, the weight reduction market will usher in a "double strong competition" situation.
In addition, Lilly's triple receptor agonist Retarutide has also made positive progress. On June 26, 2023, Lilly published a clinical research paper titled: Triple - Hormone Receiver Agonistic Retatusdefor Obesity-A Phase 2 Trial in the New England Journal of Medicine (NEJM). The research results show that Retarutide (GCGR/GIPR/GLP-1R) has a significant weight loss effect after 48 weeks of treatment with a weekly dose of 12mg. Obese individuals lost 24.2% of their weight after treatment, which is the best drug weight loss achieved so far.
But Retarutide also has adverse reactions, the most common of which is gastrointestinal reactions. These events are dose-related and most of them are mild to moderate in severity. Lower initial doses (2mg vs. 4mg) can partially alleviate them. The dose-dependent increase in heart rate peaked at 24 weeks and then decreased.