Summary of recent progress in the field of diabetes research (06.11) June 11, 2018 Source: WuXi PharmaTech 1. Taking β cells as the center, new diabetes drugs are approved for clinical use. A few days ago, ARKAY Therapeutics announced that the US FDA has accepted a new drug clinical trial (IND) application for its new diabetes drug RK-01. RK-01 is a "first-in-class" "beta-cell-centric" oral drug combination for the treatment of type 2 diabetes. It contains three components, namely metformin, valsartan and celecoxib. This clinical trial will assess the safety, tolerability, and efficacy of RK-01 in newly diagnosed and newly diagnosed patients, as well as in type 2 diabetic patients who are obese and cannot be effectively controlled by metformin alone. Type 2 diabetes is a global epidemic, which occurs after 35-40 years of age, accounting for more than 90% of diabetic patients, affecting more than 400 million people worldwide. Diabetes is the leading cause of blindness, kidney failure, heart attack, stroke and lower extremity amputation. In 2015, there were 1.6 million deaths directly caused by diabetes. Current treatments primarily control symptoms, but do not alleviate potentially complex causes. There is still huge unmet medical needs in this area. The unique formulation of RK-01 adds valsartan and celecoxib to metformin, which blocks several complementary mechanisms of inflammation and hyperglycemia, which lead to a gradual deterioration of islet beta cell function, which is exactly 2 The core of complex pathophysiology of type 2 diabetes. Valsartan is an angiotensin II receptor type 1 blocker that has been approved for the treatment of hypertension; celecoxib is a selective cyclooxygenase-2 (Cox-2) inhibitor It has been approved for the treatment of arthritis. Activation of the renin-angiotensin system (RAS) and Cox-2 in beta cells is associated with the complex pathophysiology of type 2 diabetes. Cox-2 derived pro-inflammatory prostaglandin PGE2 inhibits GLP-1 agonist-mediated glucose-dependent insulin secretion (GDIS) from beta cells. Currently, some commercially available drugs are GLP-1 agonists, but the existing treatments cannot block the damage of β-cell function caused by inflammation. While RK-01 can maintain or restore beta cells, it provides long-lasting glycemic control and even delays and prevents the use of insulin. 2. Novo Nordisk brings a new choice for hypoglycemic! Oral semaglutide effect is significant Recently, Novo Nordisk announced the results of PIONEER 2, the second phase 3a clinical trial of oral semaglutide. The 52-week open-label study evaluated the efficacy and safety of 14 mg oral smeglutide in 816 patients with type 2 diabetes who were not well controlled with metformin. Diabetes is a growing global epidemic. As of 2015, 400 million adults worldwide are affected by diabetes, of which about 100 million are in China. People with type 2 diabetes are resistant to insulin or are unable to secrete enough insulin to maintain normal blood sugar levels. Sustained high glucose levels can lead to complications of diabetes such as heart disease, stroke, kidney failure, neuropathy, lower extremity amputation and blindness. Therefore, controlling blood sugar is an urgent goal for patients with type 2 diabetes. Oral semaglutide is a novel GLP-1 analogue that promises new therapeutic options for patients with type 2 diabetes. In the PIONEER 2 trial, 816 patients were randomized to receive a daily dose of 14 mg oral semaglutide or 25 mg empagliflozin in a 1:1 ratio. The confirmatory endpoint was glycated hemoglobin (HbA1c) change and body weight change from baseline to week 26. Key secondary endpoints included HbA1c changes and body weight changes from baseline to week 52. Two different statistical methods were used in this trial to assess the efficacy of oral semaglutide: the main statistical methods were required by recent regulatory guidelines, whether or not to stop treatment and use of first aid drugs; secondary statistical methods described in treatment and not The effect of using emergency medicine. The results of the main statistical methods showed that the trial reached its main goal, demonstrating that oral smeglutide improved HbA1c better at 26 weeks, but there was no significant difference in weight loss compared with the control group. The results of the secondary statistical method showed that the HbA1c improvement in the oral semaglutide group was 1.4% at 26 weeks and 1.3% at 52 weeks, while the HbA1c improvement in the control group was 0.9% and 0.8%, respectively. At the same time, oral smeglutide showed a weight loss of 4.2 kg and 4.7 kg at 26 and 52 weeks, compared with 3.8 kg for the control group. In addition, 72% of the oral semaglutide group met the American Diabetes Association (ADA) HbA1c treatment target (less than 7.0%) at 52 weeks, compared with 47% in the control group. In terms of safety, oral semaglutide showed good tolerance in the trial and was consistent with GLP-1 therapy. 3. Treatment of type 1 diabetes, Sanofi new drug listing application accepted Recently, the FDA announced that it has accepted Sanofi's new drug application (NDA) for Zynquista (sotagliflozin). If approved, oral Zynquista will be used in combination with insulin therapy to improve glycemic control in adults with type 1 diabetes. Type 1 diabetes is a type of diabetes in which the patient's body is unable to produce insulin and causes blood sugar levels to be too high. The pathogenesis is that the pancreatic beta cells responsible for insulin production are destroyed by autoimmune responses, which may include a variety of genetic and environmental factors. There are approximately 1.25 million patients with type 1 diabetes in the United States, of which approximately 193,000 are less than 20 years old. Despite the insulin therapy, about 70% of patients with type 1 diabetes do not achieve the expected level of glycosylated hemoglobin (A1C) of less than 7.0%, so there are a large number of new oral drugs that can be used in combination with insulin. Unmet needs. Zynquista is a small molecule, research oral SGLT (Sodium-glucose transport proteins)-1 and SGLT-2 dual inhibitors developed by Sanofi in collaboration with PharmaTech's partner Lexicon Pharmaceuticals. . SGLT-1 and SGLT-2 affect the absorption and clearance of sugar (glucose) by the intestines and kidneys, respectively. By controlling the activity of these two proteins, Zynquista improves glycemic control and produces additional clinical benefits. SGLT-2 inhibitors are often used in the treatment of type 2 diabetes. The new Zynquista drug application is based on data from the inTandem clinical trial, which included three Phase 3 clinical trials evaluating the safety and efficacy of Zynquista in approximately 3,000 adult patients with insulin-independent insulin control. In inTandem1, Zynquista reached the primary endpoint of changes in A1C levels from baseline to 24 weeks. The 200 mg dose of A1C level was changed to 0.43%, the 400 mg dose was 0.49%, and the placebo was 0.08%. inTandem2 produced similar results. The third inTandem3 trial enrolled 1405 patients with type 1 diabetes with baseline A1C levels between 7% and 11%. This randomized, double-blind study showed that 400 mg of Zynquista reduced baseline A1C by 0.79% after 24 weeks of treatment compared with 0.33% in the placebo group (p < 0.001). The inTandem3 trial reached a statistically significant primary endpoint, and the results were published in the New England Journal of Medicine last September. 4. Wearable insulin delivery device effectively reduces the cost of administration Valeritas Holdings, based in New Jersey, USA, recently announced data on the company's V-Go® device compared to daily insulin injection (MDI), including efficacy in blood glucose control, insulin utilization and health care costs. Wait. Diabetes is a chronic condition in which the patient's body cannot produce or use insulin properly. About 425 million adults worldwide have diabetes, and there are nearly 30 million patients in the United States alone. Type 2 diabetes is the most common type of diabetes in the world, with more than 200 million patients worldwide, accounting for 90% to 95% of all cases of diabetes in the United States. These diabetic patients need long-term insulin supplementation to control blood sugar. Valeritas is committed to developing insulin delivery devices that improve the lives of people with diabetes. Their flagship V-Go® wearable insulin delivery device is a simple and cost-effective basal-bolus insulin delivery method that can be used like a patch. There is no need to inject more than once a day. V-Go® continuously delivers preset basal insulin delivery rates over a 24-hour period and provides intravenous drip administration as needed during meals. The retrospective cohort study of this release utilized data from the HealthCore Comprehensive Research Database (HIRD) from 07/01/2011 to 07/31/2017. During follow-up, patients with type 2 diabetes (including 118 pairs of balanced matched groups, mean baseline glycated hemoglobin HbA1c9.2%) improved their glycemic control relative to baseline (patients with HbA1c ≤ 9% after administration, anterior/posterior: V-Go 49%/69%, p<0.001; MDI 50%/60%, p=0.046). Although the baseline number of insulin drug use and diabetes-related drug costs was similar in both groups, patients who used V-Go® continued to purchase fewer insulin drugs, and the cost of diabetes-related drugs increased less, compared with MDI users, V- The total daily dose of insulin for Go® users decreased by 21% (TDD). 5. Diabetic macular edema eye disease new therapy to achieve positive top line results Biomedical company Clearside Biomedical recently announced that its Phase II clinical trial TYBEE has achieved positive top-line results. This trial evaluated the efficacy of intravitreal Eylea (aflibercept) in combination with choroidal epithelial CLS-TA (suprachoroidal CLS-TA) therapy in patients with diabetic macular edema (DME) during the 6-month evaluation period. DME is a retinal swelling caused by vascular leakage, which is the most common cause of loss of vision in diabetic patients. DME affects up to 30% of people with diabetes for 20 years or more. If untreated, about 20%-30% of patients will have moderate vision loss, and they urgently need effective treatment to improve their condition. The choroidal epithelium CLS-TA is Clearside's first in-situ treatment, a patented corticosteroid triamcinolone acetonide suspension for the posterior administration of the eye through the suprachoroidal space (SCSTM). CLS-TA reduces inflammation and other complications that cause swelling of the macula, which are the leading cause of visual impairment and blindness. The therapy is designed to quickly dispense large amounts of drug to the back of the eye, helping enough drugs reach and stay in the disease area, and extend the action time as much as possible. The TYBEE, which was announced this time, was a multicenter, randomized, blinded, controlled phase 2 clinical trial involving 71 untreated DME patients. Patients were randomized 1:1. Patients in the combined group received choroidal epithelial CLS-TA and intravitreal Eylea (weeks and March) ("combined group"). Patients in the control group received intravitreal Eylea once a month for 4 months. A sham-operated control of the choroidal epithelium, which received intravitreal Eylea treatment at 4 and 5 months, as needed. The results showed that the primary endpoint of improving the best corrected visual acuity (BCVA) compared to baseline was achieved within 6 months when assessed using the Early Diabetic Retinopathy Treatment Trial (ETDRS) scale. Patients in the combined group received an average of 12.3 ETDRS letters, compared with 13.5 ETDRS letters in the control group (E=0.664). In addition, the combination of choroidal CLS-TA and intravitreal Eylea also reached a critical secondary endpoint, ie, the patient's central retinal thickness (CST) decreased by an average of 208 microns compared to baseline at 6 months. The control group was reduced to 177 microns (p = 0.156). In addition, at 6 months, 93% of patients in the combined group had a CST reduction of more than 50%, compared with 73% in the control group. CLS-TA is generally well tolerated and no serious adverse events related to treatment are reported. In the combined group, 8.3% of patients had an IOL adverse event, which was higher than 2.9% of the control group. Cataracts occurred in approximately 5.6% of patients in the combined group and 2.9% of patients in the control group. Reference materials: [1] The US FDA Approves ARKAY Therapeutics' IND Application for Evaluating RK-01, a First-in Class 'Beta-cell-centric' Drug Combination Product in Type 2 Diabetes Patients [2] Racing to grab market share in diabetes, Novo touts its oral semaglutide win over Jardiance in PhIIIa trial [3] FDA to review ZynquistaTM (sotagliflozin) as potential treatment for type 1 diabetes [4] Valeritas' V-Go® Wearable Insulin Delivery Device Demonstrates Positive Clinical and Economic Benefits in Patients with Type 2 Diabetes [5] Clearside Biomedical Announces Positive Topline Results from Phase 2 Clinical Trial of CLS-TA Used with Eylea in Patients with Diabetic Macular Edema Original Title: Summary of Recent Progress in Diabetes Research (No. 57) Ball Valve,Sanitary Stainless Steel,Stainless Steel Tc Ball Valve,Sanitary Three Pieces Ball Valve Wenzhou Gaoya Light Industry Machinery Co.,ltd. , https://www.hongyafitting.com
