Remogliflozin was discovered and developed by Japanese firm Kissei Pharmaceutical Co and subsequently developed by GlaxoSmithKline Plc and BHV Pharma, a wholly-owned subsidiary of Avolynt Inc. Glenmark said it was the first in the world to launch Remogliflozin and India was the first country to get access to this drug.
IUPAC Chemical Name: ethyl [(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[5-methyl-1-propan-2-yl-4-[(4-propan-2-yloxyphenyl)methyl]pyrazol-3-yl]oxyoxan-2-yl]methyl carbonate,
CAS No: 442201-24-3,
Code: GSK 189075,
- WO2001016147 (Assigned to Kissei Pharmaceutical) relates to remogliflozin base,
- WO02053573 (Assigned to Kissei Pharmaceutical) relates to remogliflozin etabonate,
- WO2012006398 (Assigned to BHV PHARMA INC) relates to biphasic formulation comprising remogliflozin etabonate in immediate and controlled release phases,
- US8951976 (Kissei Pharmaceutical) relates to method of treatment for NAFL, NASH, hypernutritive fatty liver, alcoholic fatty liver disease, diabetic fatty liver and acute fatty liver using remogliflozin etabonate,
- WO2010092125 (Boehringer Ingelheim) relates to composition comprising (a) an SGLT2 inhibitor, and (b) a DPPIV inhibitor, and (c) a third anti-diabetic agent.
- Immediate release oral formulation of remogliflozin Formulation Patent (WO2018198102, claiming priority from Indian Provisional Patent Application number 201721020166 (filed on June 8, 2017) filed by Glenmark in 2017.
Remogliflozin is a selective SGLT2 inhibitor and potent anti-oxidant in clinical development for NASH and type 2 diabetes. Remogliflozin has been dosed in over 800 patients in greater than twenty clinical trials. In the previous phase 2b clinical studies, remogliflozin demonstrated HbA1c lowering greater than 1% with few adverse events. Low incidence rates of genitourinary infections and little or no increases in LDL-c, common side effects commonly associated with SGLT2 inhibitors, were also observed.
Remogliflozin has also demonstrated strong improvements in both insulin sensitivity and beta cell function as well as reductions in liver enzymes and oxidative stress. The REIN study, a global pivotal study of remogliflozin in patients with histologically confirmed NASH, is anticipated to initiate in late 2016.
Glenmark did the phase III clinical trials for Remogliflozin in India after it received certain rights to it through a licensing collaboration with BHV Pharma.
Method of action:
Remogliflozin etabonate (CAS No. 442201-24-3) is a pro-drug of remogliflozin. Remogliflozin inhibits the sodium-glucose transport proteins (SGLT), which are responsible for glucose reabsorption in the kidney. Blocking this transporter causes blood glucose to be eliminated through the urine. Remogliflozin is selective for SGLT2.
Glenmark Pharmaceuticals is bringing to India Remogliflozin etabonate, a drug used to treat adults with Type 2 diabetes.
Remogliflozin is part of the SGLT2 (sodium glucose co-transporter-2) inhibitor family. “These are a new class of drugs and different molecules of this family have been in India for more than three years,”. SGLT2 inhibitors are known to help patients additionally in terms of cardiovascular benefits and weight loss, he explained.
Remogliflozin has been studied in 26 clinical trials globally, covering about 2,500 patients from various ethnicities. Key side-effects included urinary tract infections as the sugar was excreted.
Remogliflozin Indicated to Type-2 Diabetes Mellitus:
Remogliflozin is an SGLT2 inhibitor indicated in the treatment of type-2 diabetes mellitus in adults. SGLT2 inhibitors provide glycemic control, induce weight loss and reduce cardiovascular risks. Glenmark is the first in the world to launch Remogliflozin and India is the first country to get access to the innovative drug. Others in the family of drugs include Empagliflozin, Dapagliflozin, and Canagliflozin
Glenmark received regulatory approval for Remogliflozin etabonate 100 mg tablets after successfully completing phase-3 clinical trials, which are published by Clinical Trials Registry- India (CTRI) as reiterated below
Title of the Study: A clinical trial to compare the glycaemic control and safety of insulin degludec/liraglutide (IDegLira) with insulin glargine (IGlar) as add-on therapy to SGLT2i in subjects with type 2 diabetes mellitus.
This is a 26-week randomised, active-controlled, multicentre, multinational, two-arm parallel, open-label, TTT trial in subjects with T2DM. Subjects inadequately controlled on treatment with SGLT2i ± OAD will be eligible for the trial. The trial will compare IDegLira to IGlar as an add-on to treatment with SGLT2i ± OAD. Inadequately controlled T2DM is defined as an HbA1c level of 7.0-11.0 % (53-97 mmol/mol) (both inclusive). A total of 416 subjects will be randomized using IWRS in a 1:1 manner to either of the two trial arms, IDegLira (OD) or IGlar (OD). The total trial duration will be approximately 32 weeks, consisting of a 2 week screening period, a 26-week treatment period, and two follow-up contacts (FU1 and FU2).
Title of the Study: This trial will study if it is beneficial in terms of blood sugar control, and safe, to add liraglutide to anti-diabetes medication like sodium-glucose co- transporter 2 (SGLT2) inhibitor with or without metformin.
Scientific Title of Study: “This is a 26-week, confirmatory, randomised, double-blind, placebo-controlled, multicentre, multinational, two-arm, parallel-group trial, investigating the effect and safety of adding liraglutide 1.8 mg/day to pre-trial treatment with any SGLT2 inhibitor (as monotherapy or in combination with metformin) in subjects with T2DM who have not achieved adequate glycaemic control despite stable treatment with SGLT2 inhibitor ± metformin for at least 90 days prior to trial participation. ”
Title of Study: Is SGLT2 inhibitors(diabetes drug) effective?: Test on exfoliated human kidney cell.
Brief Summary: Diabetes mellitus is estimated to affect nearly 350million of the global population and predicted to affect over 550million by 2035. In healthy (ie, glucose-tolerant) individuals, approximately 160–180 grams of glucose from plasma is filtered by the kidneys daily. Renal glucose homeostatsis includes gluconeogenesis, glucose uptake from circulation for metabolism by the kidney and renal glucose filtration followed by reabsorption. The bulk of filtered glucose i.e.90% is reabsorbed by the low-affinity/high-capacity sodium glucose co-transporter (SGLT2) located in the S1 segments of proximal tubule and residual glucose is then absorbed by the high-affinity/low-capacity SGLT1 in the S3 segment. Transcellular glucose transport is facilitated by two basolateral membrane glucose transporters: the low-affinity GLUT2 in the S1 segment and the high-affinity GLUT1 in the S3 segment. Hence almost no glucose is excreted into the urine in normoglycaemic individuals. In a healthy adult, the maximum glucose transport capacity known as the renal threshold for glucose equates to a filtration rate of 260–350 mg/min/1.73 m2, which is equivalent to a plasma glucose concentration of approximately 180 mg/dL. Once this threshold is exceeded extra glucose cannot be reabsorbed and is excreted into the urine, resulting in glycosuria. In previous studies, it has been suggested that the renal threshold in a patient with uncontrolled diabetes may increase up to 250mg/dl,presumably due to upregulation of SGLT2. The filtered glucose load at glomerulus or glomerular filtration rate (GFR)is increased with hyperglycemia and diabetes is associated with glomerular hyperfiltration. A study in humans with type 1 diabetes showed a significant increase in the renal transport maximum (Tmax) of glucose, implying possible upregulation in tubular glucose carriers. Different studies have demonstrated that SGLT2 and tubular GLUT2 expressions were increased in alloxan induced and streptozotocin induced diabetic rats respectively. Human data regarding renal expression of SGLT2 and GLUT in diabetes is limited. Studies have demonstrated increased expression of intestinal glucose carriers in patients with type 2 diabetes. No studies have been conducted in individuals with pre-diabetes regarding the expression of SGLT2 and GLUT2 in pre-diabetes in human renal proximal tubular cells.
In our study we would isolate and subculture highly differentiated proximal tubular epithelial cells from human urine. This technique, with its variations, is a significant new tool in understanding the expression and activity of renal glucose transporters in human proximal tubular epithelial cells from subjects with prediabetes, type 2 diabetes as compared to healthy volunteers. SGLT2 might be pathologically and demonstrably upregulated in PCT of prediabetics and diabetics as compared to normal subjects. It will also try to prove that glycosuria in diabetic and prediabetic subjects occurs due to upregulation of SGLT2, which may have variability (quantitative or qualitative) in expression due to differences with possible genetic polymorphism. Hence these subgroup of diabetics and pre-diabetics are much less likely to respond to SGLT2 inhibition than non glycosuric subjects. Thus, this study might ultimately have a huge impact in the future in lowering the burden of medical expenditure regarding indiscriminate use of these costly group of drugs (SGLT2inhibitors) in clinical practice.
About Avolynt, Inc.
Avolynt is a privately owned drug development company based in Research Triangle Park, North Carolina. Avolynt’s mission is to improve the lives of patients suffering from dysfunctions related to human metabolism. The Avolynt team has significant discovery and development experience across the metabolic syndrome, including diabetes, obesity, and nonalcoholic steatohepatitis (NASH). The Company is developing a novel SGLT2 inhibitor for the treatment of NASH and type 2 diabetes. Avolynt, through its wholly owned subsidiary BHV Pharma, holds an exclusive license to remogliflozin-etabonate for the global territory outside of Japan, Korea, and Taiwan. For more information about Avolynt, visit www.avolynt.com.