12:10 ET19.3% Weight Reduction, 16.5 cm Waist Circumference Decrease, SBP/DBP Reductions of 22.9/12.9 mmHg, 70.7 μmol/L Uric Acid Reduction, and 33.6% Triglyceride Reduction: BGM0504 Demonstrates Comprehensive Cardiometabolic Regulation Capabilities

, /PRNewswire/ -- Recently, BrightGene Bio-Medical Technology Co., Ltd. (hereinafter referred to as "BrightGene Bio-Medical " or "the Company") announced that its proprietary GLP-1 (glucagon-like peptide-1)/GIP (glucose-dependent insulinotropic polypeptide) dual receptor agonist, BGM0504 injection, has achieved positive topline results from a Phase III clinical trial (CTR20243983/NCT06704581) evaluating its efficacy and safety in participants with overweight or obesity. Continue Reading Overview of Phase III Clinical Trial Results of BGM0504 Injection in Weight-Reduction Change in Waist Circumference from Baseline (cm) Phase 3 (TRE) Summary of Primary Efficacy Endpoints: Body Weight Reductions in Phase 3 (TRE) Trials Change in Uric Acid from Baseline (μmol/L) Change in Blood Lipids from Baseline (%) Against the backdrop of intensifying global competition in weight management therapeutics and clinical efficacy approaching a plateau, industry focus is gradually shifting from the singular metric of "magnitude of weight loss" toward comprehensive cardiometabolic benefits and population coverage capabilities that offer greater clinical value and real-world translational impact. Consequently, the evaluation framework for weight management drugs is undergoing a fundamental transformation. Phase III data for BGM0504 demonstrated that while achieving a mean significant weight reduction of 19.3% and a waist circumference decrease of 16.5 cm, the hypertensive population experienced mean reductions in systolic and diastolic blood pressure of 22.9 mmHg and 12.9 mmHg, respectively, from baseline after 36 weeks of treatment. After 52 weeks of treatment, participants achieved a mean uric acid reduction of 70.7 μmol/L, with total body bone mineral density/lumbar spine bone mineral density/hip bone mineral density increasing by 0.3%, 1.4%, and 3.9%, respectively. Blood lipids, blood glucose, and other cardiometabolic parameters also demonstrated outstanding comprehensive improvement capabilities. Furthermore, while achieving robust efficacy, BGM0504 injection demonstrated exceptional overall tolerability, with the high-dose group showing a discontinuation rate of only 0.7%. Against the backdrop of simultaneous improvements in weight reduction, waist circumference, blood pressure, uric acid, bone mineral density, and multiple metabolic parameters, BGM0504 has evolved beyond the attributes of a singular weight management tool to embody comprehensive cardiometabolic regulation capabilities oriented toward long-term chronic disease management.19.3% Weight Reduction and 16.5 cm Waist Circumference Decrease: Exceptional Weight and Fat Loss Capabilities Demonstrated SimultaneouslyAs weight reduction enters a plateau phase, competition is shifting toward overall capabilities, with weight loss magnitude alone no longer sufficient to create significant differentiation. BGM0504 achieved a 19.3% weight reduction over a 52-week treatment period, positioning it at the upper end of the topline range for global dual-target mechanisms.Cross-dose comparisons reveal that BGM0504 demonstrates significant leadership over competing products at the low-dose level, maintains its advantage at the mid-dose level, and reaches the upper limit of the industry range at the high-dose level. BGM0504 exhibits a clear efficacy signal at the low dose (5 mg), with further enhancement at higher doses while maintaining relatively stable tolerability. This characteristic of "low-dose efficacy with dose-dependent enhancement" represents a meaningful point of differentiation among current competing products. In contrast, some competing products rely more heavily on mid-to-high doses to demonstrate efficacy, with relatively limited performance and disclosure at low-dose levels.This characteristic holds multiple implications for clinical practice. On one hand, the ability to produce substantial weight reduction at low doses helps build patient confidence early in treatment and reduces reliance on rapid dose escalation, thereby achieving a better balance between efficacy and tolerability. On the other hand, it enables potential application to a broader patient population. For example, in individuals who have not yet reached severe obesity criteria but have developed metabolic abnormalities or weight-related risks, low-dose intervention may serve as a more gentle initial therapeutic approach.Evaluating a weight management drug requires looking beyond weight reduction data to assess comprehensive outcomes, particularly changes in body shape. Waist circumference reduction reflects visceral fat loss and body shape transformation, addressing the core needs of most individuals seeking weight loss. Beyond body weight, waist circumference—a key indicator of visceral fat—also demonstrated superior results, with participants in the 15 mg dose group achieving a reduction of 16.5 cm, significantly outperforming competing products.This result indicates that its efficacy has extended from "weight change" to "risk profile improvement." Consequently, BGM0504 not only ranks in the top tier for magnitude of weight reduction, but also demonstrates advantages of earlier onset, greater waist circumference reduction, and more superior efficacy in fat distribution, a dimension that is closer to the essence of the disease.In the dimension of "who can help more people lose weight," BGM0504's advantage is even more pronounced. The proportion of participants achieving ≥5% weight loss from baseline reached 84.7%, 89.8%, and 94.6% in the 5 mg, 10 mg, and 15 mg dose groups, respectively.In the more clinically meaningful deep weight loss ranges (≥15%, ≥20%), this advantage is further amplified. In the 15 mg group, 67.3% of participants achieved ≥15% weight loss, and 48.9% achieved ≥20% weight loss—nearly half of patients achieving deep weight loss, approaching the intervention range of bariatric surgery. This indicates that its clinical value is extending from "weight management" to "metabolic state remodeling."Overall, BGM0504's core competitive advantage has shifted from "how much weight is lost" to "how much waist circumference is reduced," and ultimately to "enabling more people to achieve stable weight loss and enter the deep weight loss range." As the industry transitions from "single-point magnitude competition" to "population-level efficacy and real-world translation," the comprehensive advantages demonstrated by BGM0504 are emerging as the new competitive differentiator.SBP/DBP Reductions of 22.9/12.9 mmHg with 92.9% Target Achievement Rate, Demonstrating Antihypertensive Intervention PotentialBeyond weight reduction and waist circumference, blood pressure changes represent another noteworthy dimension in this dataset. Lilly's tirzepatide and Novo Nordisk's semaglutide did not fully investigate this population in their Phase III trials. The enrollment design itself reflects a higher level of clinical ambition. On one hand, over 60% of individuals with obesity have comorbid hypertension; the study's inclusion of patients with comorbid hypertension makes the results more aligned with the common real-world clinical scenario of "obesity + hypertension." On the other hand, the disclosure not only reports the magnitude of blood pressure reduction but also presents the blood pressure target achievement rate, elevating blood pressure from merely a "concomitant improvement" to a parameter with complete evaluative information.In the population with comorbid hypertension and uncontrolled blood pressure, mean systolic blood pressure decreased by 22.9 mmHg and diastolic blood pressure by 12.9 mmHg, with 92.9% of patients achieving target blood pressure. In contrast, previous studies of similar drugs have predominantly presented blood pressure outcomes as trend changes, with relatively limited systematic disclosure of target achievement rates. Therefore, these results provide a complementary perspective in terms of data completeness.In clinical practice, monotherapy with a single antihypertensive agent (ACEI [angiotensin-converting enzyme inhibitor, such as captopril]/ARB [angiotensin II receptor blocker, such as valsartan]/CCB [dihydropyridine calcium channel blocker, such as nifedipine]/diuretic [such as hydrochlorothiazide]) typically achieves only approximately 8–12 mmHg reduction in systolic blood pressure. Reductions exceeding 20 mmHg often require multi-mechanism combination therapy. It is important to note that this change was observed in the more challenging population of individuals with obesity and comorbid hypertension, who typically present with insulin resistance and multiple metabolic abnormalities, making blood pressure control relatively more difficult. Therefore, the simultaneous observation of improvements in both body weight and blood pressure in this population holds meaningful clinical reference value. BGM0504: Antihypertensive Efficacy vs. Clinical Standard Treatment Pathway Dimension Conventional Antihypertensive Drugs BGM0504 Monotherapy Approximately 8–12mmHg Significantly exceeds the monotherapy range Dual combination Approximately15–25mmHg Systolic blood pressurereduction near the upper limitof the range Triple combination Approximately 20–30mmHg Systolic blood pressurereduction within the range Blood pressure control rate Widely used variableacross clinical trials, core evaluation endpoint 92.9%（very high） Treatment pathway Long-term combined medication generally required for sustainedblood pressure control via a non-classical antihypertensive pathway From a broader chronic disease management perspective, hypertension and diabetes are highly comorbid in clinical practice and jointly contribute to the development and progression of cardiovascular and cerebrovascular events. According to guideline stratification, hypertensive patients with comorbid diabetes are often directly classified into higher risk categories, requiring more stringent blood pressure control targets and more urgent intervention. In this context, if metabolic intervention can simultaneously impact body weight, blood pressure, and glycemic parameters, it may produce synergistic effects on multiple metabolic abnormalities at early stages of risk. This characteristic makes the application value of these data in the continuum of "obesity—hypertension—glycometabolic abnormalities" worthy of further attention. Blood Pressure Classification and Hypertension GradingBased on Office Blood Pressure (mmHg) Classification SystolicBlood Pressure DiastolicBlood Pressure NormalBlood Pressure ＜120 AND ＜80 High-NormalBlood Pressure 120~139 AND/OR 80~89 Hypertension ≥140 AND/OR ≥90 Grade 1 Hypertension (Mild) 140~159 AND/OR 90~99 Grade 2Hypertension (Moderate) 160~179 AND/OR 100~109 Grade 3Hypertension(Severe) ≥180 AND/OR ≥110 Isolated SystolicHypertension ≥140 AND ＜90 Isolated DiastolicHypertension ＜140 AND ≥90 Note: When systolic and diastolic blood pressure fall into different grades, the higher grade should be used. Cardiovascular Risk Stratification Cardiovascular Risk Factors andMedical History Blood Pressure（mmHg） SBP 130-139 and/orDBP 85-89 SBP 140-159 and/orDBP 90-99 SBP 160-179 and/orDBP 100-109 SBP ≥180 and/orDBP ≥110 NONE Low risk Low risk Medium risk High risk 1-2 other risk factors Low risk Medium risk Medium-High risk Very High risk ≥3 other risk factors, target organdamage, CKD Stage 3, or diabeteswithout complications Medium-High risk High risk High risk Very High risk Clinical complications, CKD Stage≥4, or diabetes with complications High-Very High risk Very High risk Very High risk Very High risk Note: CKD = Chronic Kidney Disease Source: Chinese Guidelines for the Prevention and Treatment of High Blood Pressure (2024 Edition) Additionally, its safety profile is equally noteworthy. Despite the substantial magnitude of blood pressure reduction, no hypotensive events were observed during the study, suggesting that the blood pressure changes occurred in a generally stable manner. From a mechanistic perspective, this result more closely resembles comprehensive changes driven by metabolic improvement rather than a singular antihypertensive pathway.Therefore, against the backdrop of synergistic changes in weight reduction, blood pressure, and multiple metabolic parameters, BGM0504 demonstrates not only improvement in individual indicators but also coordinated effects across multiple metabolic risk factors. This characteristic provides a new observational dimension for its potential application in metabolism-related risk management.Uric Acid Reduction of 70.7 μmol/L, Demonstrating Potential Gout Benefit CapabilityBeyond blood pressure, other metabolic parameters such as uric acid also demonstrated consistent improvement trends.Uric acid, a metabolic parameter closely associated with gout, also demonstrated clinically meaningful improvement signals. Data showed that BGM0504 treatment resulted in a mean uric acid reduction of approximately 70.7 μmol/L, a magnitude that has entered the intervention range of clinical therapeutics. In the treatment of hyperuricemia, conventional urate-lowering therapies (such as the xanthine oxidase inhibitor febuxostat and the uricosuric agent benzbromarone) typically achieve reductions of approximately 60–120 μmol/L. Uric Acid Reduction Range by Intervention Pathway (μmol/L) Intervention Type Representative Drugs / Approaches Uric acid change Metabolic intervention BGM0504 -70.7μmol/L Uric acid synthesisinhibition Febuxostat, Allopurinol -60～-120μmol/L Uric acid excretion promotion Benzbromarone -60～-100μmol/L Note: Uric acid-lowering drugs are indicated for the treatment of hyperuricemia and gout. BGM0504 acts via a metabolic intervention pathway with different indications. The data are for magnitude reference only and do not constitute a therapeutic efficacy comparison.Generally, a reduction of approximately 60 μmol/L in uric acid can significantly decrease the risk of gout attacks. Therefore, this result indicates that its effect extends beyond metabolic parameter improvement and may translate into intervention potential for gout risk.Furthermore, compared to tirzepatide (SURMOUNT-1 study), BGM0504 demonstrated stronger and more balanced improvement trends across multiple core lipid parameters.For triglycerides, BGM0504 achieved a reduction of approximately 33.6%, significantly superior to tirzepatide's 24.8%, with a gap of nearly 9 percentage points. This has entered the 20%–50% range of action typical of traditional lipid-lowering agents, demonstrating an intervention intensity comparable to standard lipid-lowering agents. Additionally, low-density lipoprotein cholesterol decreased by approximately 12.7%, superior to tirzepatide's 5.8% reduction, while total cholesterol decreased by approximately 7.4%, exceeding tirzepatide's 4.8%. Based on rough calculations of the LDL-C/HDL-C ratio, this atherosclerosis-related ratio decreased by approximately 18.6% following BGM0504 treatment, suggesting that it does not merely lower a single lipid parameter, but rather reduces "bad cholesterol" while elevating "good cholesterol," thereby driving overall improvement in lipid risk profile.As an important extension of the metabolic system, bone metabolism is highly coupled with glucose and lipid metabolism as well as energy balance. At the bone metabolism level, after 52 weeks of treatment, participants across all dose groups (pooled 5 mg/10 mg/15 mg) achieved relative increases from baseline of 0.3% in total body bone mineral density (BMD), 1.4% in lumbar spine BMD, and 3.9% in hip BMD. In previous studies, weight loss is often accompanied by changes in bone mineral density. Relevant phenomena have also been observed for certain GLP‑1 receptor agonists such as semaglutide across multiple trials, and such changes are generally attributed to reduced skeletal loading following body weight reduction. Notably, in the Phase III clinical program of BGM0504, significant weight loss was accompanied by no declining trend in BMD; instead, consistent increases in bone mineral density were achieved.Body weight, blood pressure, uric acid, blood lipids, blood glucose and bone mineral density are no longer discrete endpoint indicators, but integrated into a continuous metabolic regulatory cascade. Mechanistically, BGM0504 does not merely regulate a single individual parameter; rather, it drives holistic remodeling of the metabolic system.Discontinuation Rate as Low as 0.7%, Corresponding to Higher Patient Retention and Long-Term AdherenceIn the context of outstanding efficacy performance, safety becomes one of the critical factors in product evaluation. Across different dose levels of BGM0504, treatment discontinuation due to adverse events (AEs) can more directly reflect the drug's sustainable use capability in real-world settings. Comparison of Treatment Discontinuation Due to AE Across Different Dose Groups Group BGM0504 Tirzepatide Mazdutide HRS9531 Low-dose 1.7 % 1.5 % 4.3 % 2.9 % Mid-dose 1.2 % 0.5 % 7.1 % 1.1 % High-dose 0.7 % 6.2 % 7.0 % 6.2 % At the high-dose level, BGM0504 maintained a discontinuation rate of approximately 0.7%, which not only did not increase with dose escalation but remained at a lower level, significantly below competing products by several-fold.Unlike most products where discontinuation rates increase with dose escalation, BGM0504 actually demonstrated further reduction at the high-dose level, exhibiting the rare characteristic of "dose-independent discontinuation."Further dissection of the data structure reveals that the differentiation is reflected not only in magnitude but also in result consistency. In the full analysis set (FAS) and per-protocol set (PPS), the 15 mg group achieved weight reductions of 19.2% and 19.3%, respectively, while the 5 mg and 10 mg groups also demonstrated comparable results of 14.3%/14.6% and 17.3%/16.9%, respectively. This indicates that weight reduction effects are more evenly distributed across the study population, with the majority of patients achieving clear improvement.A discontinuation rate of approximately 0.7%, combined with comparable results between the full analysis set (FAS) and per-protocol set (PPS), suggests that efficacy can be demonstrated relatively consistently across different populations and implementation conditions. This characteristic reflects, on one hand, favorable overall tolerability that helps maintain treatment continuity; on the other hand, it indicates relatively even distribution of efficacy, with results not dependent on a small subset of high-responder individuals. Its value is no longer reflected solely in magnitude of efficacy, but also in how many patients can sustain use and achieve stable outcomes.From an overall data structure perspective, the value demonstrated by BGM0504 is no longer confined to singular weight reduction magnitude. The approximately 19.3% weight reduction positions it at the current mainstream upper limit for GLP-1 class medications, while in the dimensions of population coverage and deep weight loss, it further embodies the characteristic of "enabling more patients to achieve stable weight reduction outcomes." Concurrently, the blood pressure changes observed in the population with comorbid hypertension place its antihypertensive magnitude within the range of common clinical therapeutic interventions. Further layered with simultaneous improvements in multiple parameters including blood lipids and uric acid, its action has extended from singular weight management to synergistic changes across multidimensional metabolic parameters.The term cardiometabolic generally refers to a cluster of interrelated risk factors including body weight, blood pressure, blood lipids and blood glucose. Clinically, these factors rarely exist in isolation; instead, they collectively contribute to the onset and progression of cardiovascular and cerebrovascular diseases.Cardiometabolic diseases (CMDs) represent an umbrella term for this interconnected spectrum of disorders. They encompass metabolic conditions such as obesity, type 2 diabetes and dyslipidemia, as well as cardiovascular complications including hypertension, ischemic heart disease (IHD), heart failure (HF), and peripheral vascular diseases. Recognized as the leading cause of death worldwide, CMDs are fundamentally driven by cardiovascular damage resulting from metabolic abnormalities.Within this framework, the focus of disease management has gradually shifted from single indicator control to the synergistic improvement of multiple metabolic parameters. Against the backdrop that global pharmaceutical companies widely adopt the cardiometabolic framework to define metabolism-related disorders, such clinical data imply more than a simple expansion of indication scope. It embodies an evolving therapeutic paradigm: modulating multiple cardiometabolic risk factors through a single pharmacological mechanism.In this context, BGM0504 delivers not only enhanced weight loss efficacy, but also distinctive synergistic improvements across multiple cardiometabolic dimensions, including blood pressure, glucose metabolism, lipid metabolism and uric acid levels. This profile suggests its potential value extends beyond standalone weight management to the comprehensive intervention of multiple metabolic risk factors. It offers a promising perspective for the multidimensional clinical management of cardiometabolic diseases.SOURCE BrightGene