The world's top two pure drug companies in terms of market value are Eli Lilly ($410 billion) and Novo Nordisk ($380 billion), the duopoly of GLP-1 drugs.
These two pharmaceutical companies have not entered the top ten in terms of revenue globally, but the capital market is right. In 2023Q1, the sales of Smeglutide in Novo Nordisk reached 4.2 billion US dollars, which is expected to exceed 20 billion US dollars in the whole year. However, the initial launch of Lilly Tilpoltide was much faster than Smeglutide, and some analysts predicted its peak sales of 52 billion US dollars, becoming the best selling drug ever.
The next global drug king will be born at the dual target GLP-1 without any suspense, so where is the Chinese drug king?
So, this morning, the Phase II clinical data of Xinda Biologics Masidopeptide (IBI362) 9mg in the treatment of obesity was released, with excellent data and widespread attention.
As the world's first GLP-1/GCGR dual target agonist to enter registered clinical practice, the Xinda Biologics Masidopeptide 9mg treatment regimen achieved a weight loss of 15.4% (14.7kg) compared to placebo after 24 weeks of treatment in a Chinese obese population with an average BMI of 34.3kg/m2, demonstrating potential optimal weight loss efficacy in the same class and breaking records.
Most of the domestic dual target GLP-1 is in Phase I clinical practice, and Cinda Bio Mashdopeptide has entered Phase III clinical practice in two key indications of type 2 diabetes and obesity, and is expected to win a 2-year to 3-year commercial monopoly period.
Xinda Biologics Masidopeptide is enough to be included in the history of innovative drugs. Biotech often originates from the fields of tumors and self immunity, and now extends to the fields of metabolic chronic diseases and consumer healthcare, which can alleviate competition congestion and form a diversified and healthy ecosystem. Moreover, the era calls for the emergence of super large products to drive China's innovative drugs from weak to strong. If Biotech takes the lead in entering the Breakven stage, it will play a motivating and leading role in the entire industry.
01
Four highlights, BIC weight loss potential
Marsdopeptide is the first to enter a number of registered clinical studies on obesity and diabetes among the global GLP-1R/GCGR targets, and it is also the first weight loss single drug in the world with a weight loss rate of more than 11.5% after 12 weeks of administration.
After 24 weeks of continuous use of Xinda Biologics Masidopeptide (3mg vs 4.5mg vs 6mg), compared with the placebo group, the percentage changes in body weight in the three dose groups were -8.26%, -11.60%, and -12.62%, respectively, which exceeded the injection effect of Smeglutide for 68 weeks.
The phase III clinical study of the 6mg dose group for the treatment of obesity and diabetes has been in progress before. Today, we read the phase II clinical data of the high dose 9mg for the treatment of obesity, with four highlights.
This is the world's first clinical study applicable to people with moderate to severe obesity who require surgical treatment. According to the clinical guidelines of the Chinese Surgical Treatment Guidelines for Obesity and Type 2 diabetes (2019), when BMI ≥ 37.5kg/m ² Active surgery is required at 32.5 ≤ BMI<37.5kg/m ² Metabolic surgery is recommended for first-line treatment. However, the compliance of weight loss surgery is poor, which belongs to invasive treatment, and patients will face a series of problems such as complications risk, psychological resistance, high costs, and weight rebound.
This is the first weight loss drug in the world to show the best in class compared to placebo after 24 weeks of administration, with effects comparable to weight loss surgery. After 24 weeks of treatment, the difference in the average percentage change in body weight from baseline between the 9 mg group and the placebo group was -15.4% (95% CI: -18.8%, -11.9%), P<0.001; The difference between the average change in body weight from baseline and the placebo group was -14.7kg (95% CI: -17.9kg, -11.5kg), P<0.001; At the same time, 81.7%, 65.0%, 31.7%, and 21.7% of subjects in the 9mg group showed a weight loss of at least 5%, 10%, 15%, and 20% compared to baseline, respectively, while no subjects in the placebo group showed a weight loss of 5% or more.
This is the first drug globally to develop a personalized medication regimen based on obesity levels. The 6mg solution meets a wider range of overweight and obese individuals with lower starting points (BMI 24-28kg/m ² About 340 million people are overweight; BMI≥28kg/m ², About 160 million people), the 9mg regimen is expected to become an ideal alternative to surgery for patients with moderate to severe obesity (BMI ≥ 32.5kg/m ², About 10 million people). Both options achieved the best weight loss data in their class within just 24 weeks, and the downward trend was observed to continue. The company expects longer dosing cycles to result in higher weight loss rates. Masidopeptide also provides a more concise dosing plan, requiring only two steps of dose titration to achieve a stable and sustained dose. Compared to the five to six steps of imported varieties, it is more in line with the habits and needs of the Chinese population.
Good safety and tolerability, demonstrating multiple metabolic benefits. In terms of safety, the overall tolerability and safety of the 9mg treatment group were good, and the overall dropout rate of the treatment group was lower than that of the placebo group. There were no subjects in the treatment group who terminated treatment early due to adverse events, and no serious adverse events occurred. Except for COVID-19 infection, the most common treatment related adverse events are gastrointestinal related adverse events, most of which are mild or moderate and all of them are transient. Masidoptin also exhibits various metabolic benefits, including lowering blood sugar, blood lipids, blood pressure, and even uric acid lowering benefits that have not yet been shown on smectide and tilposide.
On May 10th, Burger Ingelheim announced the latest phase II clinical data for the GLP-1R/GIPR dual target agonist BI456906 in the treatment of obese/overweight patients, with a weight loss of 14.9% after 46 weeks of treatment.
The 24 week data of Masidopeptide is better than the 46 week data of Bollinger Ingelheim.
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Treating Sugar First, Treating Fat
Obesity is a high risk factor for diabetes. About half of China's 140 million people with diabetes are overweight or obese.
Simultaneous activation of GLP-1R and GCGR can achieve multiple benefits, promoting insulin secretion, reducing blood sugar, and weight loss, as well as increasing energy expenditure and improving liver fat metabolism.
Marsdopeptide also shows its advantages in diabetes indications: it can reduce both glucose and weight, and also protect the heart, which is expected to bring benefits to the long-term course management of diabetes.
In the same overweight or obese T2DM (type 2 diabetes) patients, moderate and sustained weight loss (>5%) has been proved to improve blood sugar control, reduce the demand for hypoglycemic drugs, and bring metabolic benefits, including reducing blood pressure and blood lipids, improving insulin resistance and β Cell function; Starting from a weight loss of 10-15%, the probability of T2DM remission increases as the weight loss percentage increases.
In the second phase of clinical treatment of diabetes with 6mg Marsdopeptide, the hypoglycemic trend of Marsdopeptide was superior to Dulagopeptide. In the third phase of clinical treatment, the head to head control long-acting Dulagopeptide 1.5mg was also selected.
At week 20, 49% of patients in the 6mg group achieved a weight loss of over 5% and HbA1c (glycated hemoglobin, reflecting average blood sugar levels for the past 8-12 weeks) was below 7%. Only 12% of patients in the 1.5mg group achieved the same effect, while no one in the placebo group achieved this effect.
With its excellent hypoglycemic effect and unique weight management advantages, Xinda Biological Mashdopeptide will gradually erode the market space of the previous generation of diabetes therapy.
03
Once in a Decade Super Product
Will weight loss pills repeat the PD-1 trap of being trapped in the urine of domestic companies who like to cluster on popular tracks?
The intensity of competition varies.
According to the announcement of Novo Nordisk, the prescription penetration rate of GLP-1 receptor agonist in the domestic market is low, only 2%, and there is no obesity indication approved for GLP-1 receptor agonist in China so far, and a huge blue ocean market has not really started.
The increasing market capacity in the later stage can also ease the level of competition. The overweight and obesity rates in China are rapidly increasing. According to the "Consensus of Chinese Obesity Prevention and Control Experts", more than 50% of adults and about 20% of school-age children in China are overweight or obese; In some cities, the overweight and obesity rates among children and adolescents have reached 40%. According to Frost Sullivan's analysis, the number of obese patients in China is expected to reach 329 million by 2030. Obesity is not only related to metabolism, but also one of the main risk factors for many cardiovascular diseases. According to "Health Policy and Public Health Applications in China", it is predicted that by 2030, the medical expenses attributed to overweight/obesity in China will reach around 418 billion yuan, accounting for approximately 21.5% of the total national medical expenses.
The product levels are different.
GLP-1 receptor agonists are showing a trend of replacing short-term effects with long-term effects and replacing single targets with dual targets. The products are classified into different levels based on generation and efficacy. As the first domestically produced long-term dual target GLP-1 receptor agonist, Xinda Biologics Masidopeptide is equivalent to sitting at the top of the pyramid.
The efficacy of single target GLP-1 drugs in moderate to severe obesity is limited, and even after one year of treatment, it is difficult to achieve a 15% weight loss compared to placebo compared to baseline.
Compared to single target GLP-1, dual target GLP-1 can achieve better hypoglycemic and weight loss effects, making it a mainstream drug in the future.
The starting advantage is different.
Xinda Biologics Masidu Peptide has the advantage of starting first and crushing opponents. The 6mg dose group is expected to read out the complete clinical data of three phases by the end of this year or early next year, and then apply for NDA. It is expected to be launched by the end of 2024 or early 2025, not only leading the other domestic dual target GLP-1 by two to three years, but also even earlier than the domestic smeglutide generic drug (weight loss indication). The domestically produced short acting GLP-1 receptor agonist generic drug (Liraglutide weight loss indication) was first launched this year, but it is only a temporary transitional product.
The product attributes are different.
Weight loss pills follow the logic of consumer goods, with the most recognizable products, the lowest cost of public information search, and a first mover advantage+channel advantage. Xinda Biotech is expected to seize the main market share.
In situations where sales capabilities are comparable, who can win depends on product performance, but the latter have no technological iteration or differentiation advantages compared to Masalidomide, making it difficult to surpass.
Obese patients have strong Willingness to pay. According to data from the 2020 China Health Slimming Industry Development Monitoring conducted by iMedia Consulting, 91.6% of overweight or obese Chinese adults surveyed are willing to pay for weight loss, with 57.8% willing to pay more than 1000 yuan. Unlike PD-1, which heavily relies on medical insurance, weight loss pills are supported by the self funded market.
At present, there are 250 million people in China who belong to Generation Z and are gradually becoming the main force of the new consumer generation. They deconstruct traditional values centered on marriage and real estate, are enthusiastic about self pleasing consumption, pay more attention to body shape management, and are not highly price sensitive.
So, a price war similar to PD-1 is difficult to repeat, and the possibility of a huge weight loss market collapsing is very small.
It can bring multiple clinical benefits without the risk of hypoglycemia, and is in line with the preferences of the new consumer generation. The patient base is large, with a wide range of indications (gradually expanding to kidney disease, cardiovascular disease, NASH). From any perspective, the dual target GLP-1 receptor agonist can be considered a once in a decade super product.
