Monotherapy for glucose lowering surpasses tirzepatide, and in head-to-head combination therapy it is superior to semaglutide: Brightgene Bio-Medical Technology Co., Ltd. (688166.SH) BGM0504 competes for the global glucose-lowering benchmark.

Brightgene Bio-Medical Technology Co., Ltd. (688166.SH) BGM0504 injection has successively achieved two positive Phase III clinical results for glucose lowering, positioning its competitive reference against the two global glucose-lowering benchmarks, tirzepatide and semaglutide. In the monotherapy study, after 32 weeks of treatment in the BGM0504 10 mg group, HbA1c decreased by 2.6 percentage points from baseline, 93.4% of patients achieved HbA1c <7%, and 51.8% achieved the stricter HbA1c <5.7% target. Its reduction magnitude exceeded the listed monotherapy study results for tirzepatide and semaglutide, and the proportion achieving strict glycemic control targets also demonstrated outstanding performance. In the combination therapy study on a background of oral glucose-lowering drugs, the BGM0504 10 mg group was head-to-head superior to the semaglutide 1.0 mg group in the Week 32 primary endpoint analysis, with an additional HbA1c reduction of approximately 0.46 percentage points, and maintained this advantage through Week 52; the 5 mg group also achieved statistical superiority in the Week 52 supplementary analysis. Using the tirzepatide SURPASS-2 study as an external reference, the BGM0504 10 mg group also showed numerical advantages in glucose-lowering magnitude and HbA1c <5.7% achievement rate. From the larger reduction and high achievement rate in monotherapy to the direct superiority and sustained glycemic control in combination therapy, BGM0504 is challenging the global glucose-lowering benchmarks with data from two Phase III studies. Monotherapy reduction surpasses tirzepatide; strict glycemic control target achievement rate outstanding This monotherapy Phase III study was a multicenter, randomized, double-blind, placebo-controlled parallel-group study that enrolled 227 subjects, with a mean baseline HbA1c of approximately 8.3%. Subjects received BGM0504 5 mg, 10 mg, or placebo once weekly by subcutaneous injection, with a core treatment period of 32 weeks, followed by a 20-week extended treatment period. Based on the treatment-regimen estimand (TRE), at 32 weeks of treatment, HbA1c in the BGM0504 5 mg and 10 mg groups decreased by 2.2% and 2.6% from baseline, respectively, while the placebo group decreased by 0.51%. Both dose groups achieved statistical superiority versus placebo, and the 10 mg group also achieved statistical superiority versus the 5 mg group. Under the efficacy estimand (EE), the reductions in the two dose groups were likewise approximately 2.2% and 2.6%, respectively, with highly consistent results between the two estimand analyses. Comparing this result with tirzepatide monotherapy studies, BGM0504's reduction magnitude was numerically prominent. In the tirzepatide China monotherapy Phase III study SURPASS-CN-MONO, by TRE, the HbA1c reductions after 40 weeks of treatment in the 5 mg, 10 mg, and 15 mg groups were 2.19%, 1.75%, and 2.03%, respectively.[1] The reductions in the BGM0504 5 mg and 10 mg groups after 32 weeks of treatment were 2.2% and 2.6%, respectively; the 5 mg group's reduction was already numerically higher than all three above dose groups, and the 10 mg group further widened the reduction. Key efficacy comparison in the monotherapy study: HbA1c reduction magnitude Note: Reductions in the figure use the TRE estimand and have not been adjusted for placebo effect [13]. In the global SURPASS-1 study, the 40-week TRE reductions in the tirzepatide 5 mg and 10 mg groups were 1.75% and 1.71%, respectively; in the semaglutide SUSTAIN-1 study, the 30-week reductions in the 0.5 mg and 1.0 mg groups were 1.45% and 1.55%, respectively.[2,3] From this cross-study numerical comparison, the BGM0504 5 mg group already showed a larger glucose-lowering magnitude at 32 weeks, with a reduction numerically higher than the listed tirzepatide and semaglutide dose groups; the 10 mg group's reduction further reached 2.6%, the most prominent among the comparisons with the other study data. In addition to the mean reduction, another outstanding feature of BGM0504 was the high HbA1c target achievement rate. At 32 weeks of treatment, the proportions achieving HbA1c <7% in the 5 mg and 10 mg groups were 82.2% and 93.4%, respectively, versus 21.7% in the placebo group; the proportions achieving HbA1c <5.7% were 39.9% and 51.8%, respectively, versus 2.6% in the placebo group. This means that more than 90% of patients in the 10 mg group achieved the HbA1c <7% target, and more than half achieved the stricter HbA1c <5.7% level. By TRE, the HbA1c <7% achievement rates listed for the tirzepatide 5 mg and 10 mg groups in SURPASS-CN-MONO were 90.4% and 79.2%, respectively, and the HbA1c <5.7% proportions were 40.4% and 29.8%, respectively.[1] Both achievement rates in the BGM0504 10 mg group were numerically higher than these two dose groups; among them, the 51.8% strict achievement rate was 11.4 percentage points higher than the higher value of 40.4% in the two groups. Among the 5 mg and 10 mg groups listed in the global SURPASS-1 study, the HbA1c <5.7% achievement rates for tirzepatide were 30.9% and 26.8%, respectively; in the semaglutide SUSTAIN-1 study, the HbA1c <7% achievement rates in the 0.5 mg and 1.0 mg groups were 74.0% and 72.0%, respectively.[2,3] These data comparisons provide a reference for understanding BGM0504's glycemic control performance and also show that it has surpassed tirzepatide and semaglutide in both HbA1c reduction and achievement rates. Note: Achievement rates in the figure use the TRE estimand; the SURPASS-CN-MONO column shows the 5 mg and 10 mg groups, and SUSTAIN-1 does not list HbA1c <5.7% data.[1,3] In terms of safety and tolerability, according to the announcement, BGM0504 performed well overall in the monotherapy study. The vast majority of common gastrointestinal adverse reactions were transient mild to moderate and recovered within a relatively short time without intervention or after only simple symptomatic treatment. During the treatment period of up to 52 weeks, the proportion of trial group discontinuations due to adverse events and the incidence of severe hypoglycemic events were both 0. Combination therapy head-to-head superior to semaglutide; glucose-lowering performance benchmarked against tirzepatide In addition to the monotherapy study, another Phase III study of BGM0504 used semaglutide 1.0 mg as an active comparator to directly test its ability to further control blood glucose on a background of metformin and other oral glucose-lowering drugs. The study enrolled Chinese adults with type 2 diabetes whose blood glucose remained inadequately controlled after prior oral medication treatment, with once-weekly subcutaneous injection, a 52-week treatment period, and the primary endpoint being the change in HbA1c from baseline at Week 32. Key efficacy results showed: at Week 32 of treatment, HbA1c in the BGM0504 injection 5 mg group, 10 mg group, and semaglutide 1.0 mg group decreased from baseline by 2.05%, 2.41%, and 1.95%, respectively. The BGM0504 10 mg group reduced HbA1c by an additional 0.46 and 0.36 percentage points compared with the semaglutide 1.0 mg group and the BGM0504 5 mg group, respectively, with both comparisons achieving statistically significant superiority. By Week 52, HbA1c in the three groups decreased from baseline by 2.07%, 2.34%, and 1.88%, respectively; the BGM0504 10 mg group reduced HbA1c by an additional 0.46 and 0.27 percentage points compared with the semaglutide 1.0 mg group and the 5 mg group, respectively, both achieving statistically significant superiority. The BGM0504 injection 5 mg group also showed sustained glucose-lowering effects. The Week 52 supplementary analysis showed that the 5 mg group reduced HbA1c by an additional 0.19% compared with the semaglutide group, achieving statistically significant superiority. The above results indicate that the 10 mg group demonstrated a clear glucose-lowering advantage at both observation time points, while the 5 mg group showed superiority versus semaglutide in the Week 52 supplementary analysis, further highlighting the long-term glycemic control performance of the 5 mg group. Note: The above are direct comparisons within the same combination therapy study using the TRE estimand; the 5 mg group achieved non-inferiority at 32 weeks and superiority in the 52-week supplementary analysis, and the 10 mg group achieved statistical superiority at both 32 and 52 weeks. Benchmarked against the global glucose-lowering standard tirzepatide, BGM0504 also performed prominently in the combination therapy study. By TRE, in the SURPASS-2 study, the HbA1c reductions after 40 weeks of treatment in the tirzepatide 5 mg and 10 mg groups were 2.01 and 2.24 percentage points, respectively[4]; in the BGM0504 study, the reductions after 32 weeks of treatment in the 5 mg and 10 mg groups were 2.05 and 2.41 percentage points, respectively. In this cross-study numerical comparison, the additional glucose-lowering magnitude of the BGM0504 10 mg group was higher than that of the tirzepatide 5 mg and 10 mg groups, demonstrating strong glucose-lowering competitiveness. Note: The BGM0504 comparison with the semaglutide control in this study uses 32-week data, while tirzepatide uses 40-week data from SURPASS-2, using the TRE estimand. The mean baseline HbA1c was 8.43% in the BGM0504 study and 8.28% in SURPASS-2[4]; cross-study comparisons are for descriptive reference only. HbA1c achievement rates further demonstrated the benefit in the head-to-head study. At 32 weeks of treatment, the proportion achieving HbA1c <7% in the BGM0504 10 mg group was 85.5%, versus 77.5% in the semaglutide group, 8.0 percentage points higher; the proportions achieving the stricter HbA1c <5.7% target were 42.9% and 22.6%, respectively, with the BGM0504 group 20.3 percentage points higher. For the stricter HbA1c <5.7% target, the 32-week achievement rates in the BGM0504 5 mg and 10 mg groups were 29.8% and 42.9%, respectively, both higher than the 40-week rates of 27.0% and 40.0% in the same-dose groups listed in SURPASS-2.[4] In terms of safety and tolerability, according to the announcement, BGM0504 performed well overall in the combination therapy study. The vast majority of common gastrointestinal adverse reactions were transient mild to moderate and recovered within a relatively short time without intervention or after simple symptomatic treatment. During the 52-week treatment period, the proportion of trial group discontinuations due to adverse events related to the study drug was only 0.54%, and no severe hypoglycemic events occurred. Dual breakthrough in reduction and achievement rates; BGM0504 demonstrates potent glucose-lowering strength Evaluating a glucose-lowering drug requires combining the mean HbA1c reduction with patients' actual achievement rates. The former reflects overall glycemic improvement, while the latter reflects the proportion of patients reaching preset HbA1c targets. The core value of BGM0504's data this time lies in the larger reduction and higher strict achievement rate under the TRE estimand in the monotherapy study, as well as the direct superiority evidence versus semaglutide in combination therapy. Numerical leadership across studies and statistical superiority within the same study should be understood separately. In the monotherapy Phase III study, the BGM0504 10 mg group demonstrated potent glucose-lowering efficacy: under the TRE estimand, HbA1c decreased by a mean of 2.6 percentage points, as many as 93.4% of participants achieved the HbA1c <7% standard, and 51.8% of participants achieved the stricter HbA1c <5.7% target. In the combination therapy study targeting patients inadequately controlled on oral drugs, BGM0504 also performed impressively: head-to-head comparison showed that its 10 mg group's HbA1c reduction at the Week 32 primary efficacy endpoint was significantly better than semaglutide 1.0 mg (achieving statistical superiority), and the HbA1c <7% and <5.7% achievement rates were 8.0 and 20.3 percentage points higher, respectively. This reduction superiority remained robust at Week 52, supporting its potent glycemic control performance sustained through 52 weeks. Considering the choice of comparators across different studies, the superiority achieved by BGM0504 directly against semaglutide 1.0 mg, and the maintenance of this advantage through Week 52, provide a more direct basis for evaluating its incremental value relative to established glucose-lowering therapies. Professor Ji Linong, Principal Investigator of the Phase III clinical study of BGM0504 injection for adults with type 2 diabetes and Director of the Endocrinology Department at Peking University People's Hospital, said: "I am very satisfied with the results of the two Phase III clinical trials of BGM0504 injection conducted in adults with type 2 diabetes, both as monotherapy and combination therapy! Among participants receiving monotherapy in the study, HbA1c reduction reached 2.6%, the proportion of participants achieving HbA1c <7% reached 93.4%, and the proportion reaching normal HbA1c levels of HbA1c <5.7% reached 51.8%. In the combination therapy group, the head-to-head comparison of BGM0504 versus semaglutide showed that the 10 mg group met the prespecified non-inferiority criteria and achieved statistical superiority versus semaglutide at both 32 and 52 weeks; the 5 mg group also met the non-inferiority criteria at 32 weeks and achieved superiority in the 52-week supplementary analysis; in this treatment group, HbA1c reduction at 32 weeks reached 2.41%, the proportion of participants achieving HbA1c <7% reached 85.5%, and the proportion reaching normal HbA1c levels of HbA1c <5.7% reached 42.9%. Moreover, key secondary indicators such as fasting blood glucose were significantly improved, and cardiovascular indicators such as body weight and blood pressure showed clear benefits. More encouragingly, BGM0504 demonstrated excellent safety. I very much look forward to these two studies providing key supporting evidence for the approval and launch of BGM0504, offering an efficacious and safe treatment option for the vast number of patients with type 2 diabetes." Dr. Yuan Jiandong, Chairman of Brightgene Bio-Medical Technology Co., Ltd., said: "At present, the chronic disease management philosophy for adult diabetes in China is continuously upgrading. It is no longer merely satisfied with controlling blood glucose values, but is shifting toward comprehensive management that also addresses overall cardiovascular metabolic improvement, reduces complication risk, and enhances long-term quality of life. For the vast number of patients with type 2 diabetes, if a drug can simultaneously improve key metabolic indicators such as body weight, blood pressure, and blood lipids, it will bring entirely new value to long-term disease management. We will make every effort to accelerate the new drug application for BGM0504, and we also look forward to this innovative peptide drug benefiting patients as soon as possible, carrying forward our vision of continuously empowering chronic disease management with innovative drugs and benefiting the vast number of patients, and providing a new treatment option for the Chinese type 2 diabetes population that addresses both glucose lowering and metabolic protection." Competitor data sources [1] Tirzepatide (Eli Lilly) SURPASS-CN-MONO study. Yin Y, Ma J, Liu D, et al. Tirzepatide monotherapy in Chinese patients with early type 2 diabetes: A randomized, double-blind, placebo-controlled phase 3 trial (SURPASS-CN-MONO). Med. 2026;7:101183. The 40-week TRE reductions and HbA1c achievement rates cited in the text are shown in the publicly available supplementary materials Table S2 and Figure S2 (Table S2 begins on page 5 of the supplementary PDF). DOI: 10.1016/j.medj.2026.101183 publicly available supplementary materials [2] Tirzepatide (Eli Lilly) SURPASS-1 study. Rosenstock J, Wysham C, Fras JP, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021;398(10295):143155. The 40-week TRE reductions and HbA1c <5.7% achievement rates cited in the text are shown in the publicly available supplementary materials Table S6 (Treatment-Regimen Estimand, supplementary PDF beginning on page 15). DOI: 10.1016/S0140-6736(21)01324-6 [3] Semaglutide (Novo Nordisk) SUSTAIN 1 study. Sorli C, Harashima SI, Tsoukas GM, et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Lancet Diabetes Endocrinol. 2017;5(4):251260. The 30-week HbA1c reductions cited in the text are shown in Table 2, and the HbA1c <7% achievement rates are shown in Table 3. DOI: 10.1016/S2213-8587(17)30013-X [4] Tirzepatide (Eli Lilly) SURPASS-2 study. Fras JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021;385:503515. The 40-week TRE reductions cited in the text are shown in the main text and Figure 1A, the HbA1c <5.7% achievement rates are shown in Figure 1C; the mean baseline HbA1c is shown in Table 1. DOI: 10.1056/NEJMoa2107519