——2024 Xiangya International Diabetes and Immunology Forum Symposium Wonderful Express
In recent years, glucagon-like peptide 1 receptor agonists (GLP-1RA), as one of the new hypoglycemic drugs that have attracted much attention, have been improving their guideline status, but their clinical use rate and compliance are still facing challenges, and there is an urgent need for long-acting GLP-1RA with easier use to meet the treatment needs. The new GLP-1RA weekly formulation of vipernatide is a class 1 innovative drug independently developed by Paige Biotech, which has the advantages of rapid and potent, stable and durable, good safety, no need to titrate once a week, and comprehensive benefits, and has attracted great attention from the phase III clinical study in China.
On April 20, 2024, at the special meeting held during the 19th Xiangya International Diabetes Immunology Forum, the principal investigator (PI) presented the results of two pivotal phase III clinical studies of vipenatide. Professor Zhou Zhiguang (PI of Phase III.a clinical trial) from the Second Xiangya Hospital of Central South University presided over the meeting, and Professor Ji Linong (PI of Phase III.b clinical trial) from Peking University People's Hospital announced and interpreted the important results. What is the efficacy and safety of viperatitide in lowering blood sugar?
Statement by the President
Professor Zhou Zhiguang pointed out that with the expansion of hypoglycemic drugs and the accumulation of clinical research evidence, the treatment concept of type 2 diabetes mellitus (T2DM) has also evolved from simple hypoglycemic to individualized, comprehensive and patient-centered. As one of the new hypoglycemic drugs that have attracted much attention in the field, GLP-RA has been rising in the status of domestic and foreign guidelines, leading the reform of diabetes treatment and bringing a new choice for the comprehensive management of patients with T2DM.
Vipenatitide is a novel GLP-1RA weekly formulation independently developed by Paige Biotech, a leader in the domestic biomedical field, and its New Drug Application (NDA) for the treatment of T2DM in China has been accepted by the National Medical Products Administration in September 2023. As one of the PIs of the pivotal Phase III clinical study, Professor Zhou expressed his deep honor and pride to gather with many diabetes experts to witness the release of the Phase III clinical data of the class 1 new drug vipenatide. In fact, vipenatitide is not only carrying out phase III clinical trials in China, but also conducting clinical studies in the United States and other overseas countries, and it is expected that this domestic original innovative drug can bring good news to more diabetic patients in China and even around the world in the future.
Interpretation of the results of the phase III clinical study of vipenatitide
Professor Ji Linong gave a detailed introduction and in-depth analysis of the phase III clinical data of vipenatitide, and interpreted its characteristics and potential clinical value in the treatment of T2DM.
01 Current status of GLP-1RA: The status of the guidelines is constantly improving, but the actual use rate is low, and drug compliance needs to be improved urgently
Professor Ji first emphasized the important therapeutic status of GLP-1RA and the need for further optimization. Chinese patients with T2DM have the characteristics of high prevalence, low compliance rate, and often combined with a variety of metabolic factors, which require comprehensive management. GLP-1RA has been listed as a first-line treatment for patients with T2DM due to its multiple benefits, and has been gradually improved in major guidelines at home and abroad, but its actual clinical use rate is still low [1], which is closely related to its poor treatment compliance. The key factors influencing GLP-1RA adherence include dosing frequency, dose titration, and ease of use of injection devices[2]. The weekly formulation of GLP-1RA without dose adjustment and easy injection can be simplified to further optimize the treatment of T2DM. Viperatitide was developed based on clinical needs, and the research is progressing well, and the phase III clinical data will provide important evidence for the efficacy and safety of its treatment.
Phase 02III clinical data revealed: Based on evidence, vibenatitide meets the treatment needs of patients with T2DM
According to Professor Ji, the two pivotal Phase III clinical studies are designed to be multicenter, randomized, double-blind, placebo-controlled, to evaluate the efficacy and safety of viperatitide alone and in combination with metformin in patients with T2DM, respectively (Figure 1):
Phase III.a clinical study: A total of 273 patients with T2DM with poor glycemic control after diet and exercise intervention were randomly given vepenatid 150 μg once a week subcutaneously or placebo for 24 weeks in the double-blind treatment period, and then entered the open extension period, and both groups were treated with vepenatid for 28 weeks.
Phase III.b clinical study: A total of 620 patients with T2DM with poor glycemic control treated with metformin were included in the double-blind treatment period, and were randomly combined with vipernatide 150 μg once a week subcutaneously or placebo for 24 weeks on the basis of metformin treatment in the double-blind treatment period, and then entered the open extension period, and both groups of patients were treated with metformin combined with vipenatide for 28 weeks.
Figure 1. Viperatitide phase III clinical study design
The results of two phase III clinical studies have consistently confirmed the clinical hypoglycemic efficacy of viperatitide alone or in combination with metformin in the treatment of T2DM:
Rapid and potent: HbA1c decreased by 0.82% at 4 weeks of monotherapy (Fig. 2), and by 1.37% (Fig. 2), 1.263 mmol/L, and 2.521 mmol/L at 24 weeks of monotherapy, respectively[3];
Durably stable: the change from baseline in HbA1c remained stable at 52 weeks of monotherapy (Fig. 2) [3];
Symptomatic treatment: significantly improve C-peptide level and β cell function[3];
Overall benefits: 4.77 kg weight reduction (BMI >32 kg/m2 in patients), blood pressure, lipid regulation, and cardiovascular risk factor improvement[3];
Safety targeted: The incidence of hypoglycemia is low, and the most common adverse reactions are gastrointestinal reactions, but the incidence is low and well tolerated [3].
Figure 2. Change from baseline in HbA1c during 52 weeks of vipenatitide monotherapy
Conclusion and outlook
GLP-1RA plays an important role in the comprehensive management of diabetes, and in order to improve its poor compliance and low usage rate, it has become a new trend in the development of GLP-RA weekly formulations (such as viperatide). The data of the phase III clinical study of viperatitide have been announced, and the results have confirmed that it combines the efficacy, safety and simplicity of hypoglycemic treatment, and is a new long-acting GLP-1RA weekly preparation that can meet the treatment needs of patients with T2DM, and the clinical application prospect is promising.
We look forward to seeing more detailed data from the Phase III clinical study as soon as possible, and also look forward to this excellent domestic innovative drug being approved for marketing as soon as possible, and going abroad to benefit more diabetic patients and contribute to the innovation and development of diabetes treatment." Let's wait and see!
About Vipenatide:
Vipenatitide is a long-acting GLP-1RA weekly preparation independently developed by Paige Biotech, and is a Class 1 new drug that has been supported by the national "Major New Drug Creation" Science and Technology Major Project. The drug is a GLP-1 peptide derivative modified by pegylation (PEG) technology, and can retain the biological activity of the peptide in a high proportion, so as to effectively reduce the clinical dose and achieve once-a-week administration while balancing the activity, clearance and safety of GLP-1RA. Vipenatide is a single-dose, dose-free titration-free administration method combined with a disposable auto-injection pen, which is simple to operate and only requires two steps, helping to improve the convenience and quality of life of patients. The pivotal phase III clinical study [3] showed that after 24 weeks of viperatitide monotherapy, HbA1c was reduced by 1.37%, which was significantly higher than that in the placebo group, and at 52 weeks, HbA1c showed a further downward trend from baseline, with a reduction of 1.39%. Observing the whole treatment cycle, the change of HbA1c from baseline remained stable, and the HbA1c decreased by 0.82% in the fourth week of treatment, and the effect of vibenatitide was rapid.
In addition to the absolute reduction in HbA1c, treatment attainment is also an important goal of hypoglycemic therapy, and the HbA1c attainment rate of 24 weeks with vibenatitide monotherapy was 50.4%. In addition to the above advantages, vipenatitide also has the effect of significantly improving the level of C-peptide, pancreatic islet β cell function index and insulin resistance index. For overweight and obese T2DM populations, the weight loss is more significant with the increase of BMI base. In patients with T2DM with a BMI > 32 kg/m2, 52 weeks of treatment with vibenatitide reduced the mean body weight by 4.77 kg. In addition, vibenatid has a significant role in reducing blood pressure and lipids and improving cardiovascular risk factors. At the same time, viperatitide has a good safety profile, with a 26-week incidence of confirmatory hypoglycemia of 0, and a low incidence of gastrointestinal adverse reactions, with the incidences of nausea, vomiting, abdominal distension, and diarrhea being 8%, 5.1%, 5.1%, and 7.3%, respectively, and is well tolerated. The NDA for the treatment of T2DM was accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in September 2023.
About Paige Bio
Paige Biopharma is a biopharmaceutical company dedicated to the integration of R&D, production and sales of innovative drugs in the field of chronic disease treatment, with the mission of "being a health messenger for patients with chronic diseases". Since its establishment in 2008, the company has always focused on the in-depth cultivation and exploration of innovative therapies in the field of chronic disease treatment, and has built a R&D pipeline with metabolic diseases as the core and covering a wide range of chronic diseases, covering type 2 diabetes, non-alcoholic fatty liver disease, obesity, hyperuricemia, gout, opioid-induced constipation and other disease areas. A number of products in its R&D pipeline, including long-acting GLP-1/GCG receptor dual agonists and opioid receptor antagonists, have shown high potential and prospects. At present, Paige Biotech's core product, long-acting GLP-1 receptor agonist viperatitide injection, has completed phase III clinical trials and is expected to be approved for marketing in China in the near future. At the same time, Paige Biotech has made layout planning for the global market, striving to promote excellent domestic innovative drugs to the world and benefit more patients with chronic diseases.
Bibliography:
1. Limonte C.P., et al. J Diabetes Complications. 2022; 36(6): 108204.
2. Lee DSU, et al. Diabetol Metab Syndr. 2022; 14(1): 12.
3. Data on file.