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- Molecule continues to demonstrate potential to be the best-in-class in achieving glycemic control with low incidence of hypoglycemia and neutral effect on body weight
- Phase IIb successfully completed
- Global Phase III trials likely to start by end 2009
- IND approved by USFDA
Mumbai, INDIA | June 24, 2009 | In the recently completed 12 week Phase IIb clinical trial in 494 patients with type 2 diabetes mellitus (T2DM), ‘Melogliptin’, Glenmark’s investigational medicine from a new class of diabetes treatments called dipeptidyl peptidase 4 (DPP-4) inhibitors, improved glycemic control in patients with type 2 diabetes mellitus and exhibited excellent safety and tolerability profile. In addition, patients taking Melogliptin experienced low incidence of hypoglycemia and neutral effect on body weight.
In this 12-week, randomized, double-blind, placebo-controlled, parallel group study, Melogliptin significantly reduced HbA1c from baseline as compared to placebo with a mean average reduction of 0.75% in patients receiving 50mg twice daily dose (p<0001) and 0.60 % in patients receiving 100 mg once daily dose (p<.0001).
In a subgroup of patients with higher baseline HbA1c of 8.5%-10%, Melogliptin reduced HbA1c from baseline as compared to placebo with a mean average reduction of 0.88 % and 1.05 % in patients receiving 100mg once daily dose and 50mg twice daily dose respectively, which compares favorably to reported results of other DPP-4’s.
Beta cell dysfunction, characterized by decreased ability to produce adequate insulin is hallmark of type 2 diabetes mellitus. In this study, 50mg twice daily Melogilptin produced significant improvement in measures of pancreatic beta cell function (an increase in HOMA-β, suggesting enhanced insulin release). With these results Melogliptin demonstrates potential for offering class leading improvements in the glycemic control and metabolic function.
Glenmark has recently received IND approval from the USFDA to carry out a clinical study in the US
“Global Phase III trials have been planned with Melogliptin and are due to start at the end of 2009 following regulatory approvals. These studies are designed to evaluate the compound both as monotherapy and in combination with other anti-diabetic therapies in patients with type 2 diabetes mellitus”. said Mr Glenn Saldanha, MD & CEO, Glenmark Pharmaceuticals Limited. He further added “With this phase II study being successful, we take a step closer towards our objective of becoming the first Indian company to have a truly global innovative drug for the world”
"Ever since diabetes was first identified, researchers have been looking for oral compounds that can restore normal glycemic control and abnormal beta cell function in a physiological manner from the diseased state. The results from this Melogliptin study hold great promise, both in the short and long term, for patients with diabetes of all severities," mentions Dr John Efthimiou, Chief Medical Officer, Glenmark Pharmaceuticals Limited.
Glenmark continues to be in discussions with various licensing partners to take the molecule forward.
Melogliptin, previously known as GRC 8200, inhibits an enzyme called DPP-4, resulting in an increase of circulating levels of GLP-1, a crucial incretin hormone. Incretin hormones are secreted from the intestines in response to a meal. GLP-1 stimulates the beta cells, located in the islets of the pancreas, to produce insulin, reducing the amount of glucose circulating in the blood in a physiological and proportional manner. GLP-1 also reduces the secretion of glucagon from the islets' alpha cells. People with type 2 diabetes mellitus also produce high levels of glucagon, signalling the liver to produce glucose. By restoring the production of insulin and suppressing elevated glucagon, Melogliptin improves glucose control and normal pancreatic function. Melogliptin is likely to be launched in 2013.
In this study, 494 patients with type 2 diabetes mellitus, with mean age 51 years (range was 30 years to 80 years) and with baseline HbA1c of 7% to 10% (mean 8.4%) were randomized to one of five treatment groups: placebo; Melogliptin (25 mg, 50 mg, or 100 mg) once daily; or Melogliptin 50 mg twice daily. Treatment with Melogliptin was generally well tolerated and patients experienced low incidence of hypoglycemia and neutral effect on body weight.
About DPP IV Inhibitors:
The DPP- IV inhibitors have been the most promising class of drugs for the treatment of type 2 diabetes mellitus. In just a short span of two years and with just two products in the market i.e. Januvia and Galvus, this class of drugs has already emerged as the fastest growing class among oral anti-diabetics achieving annual global sales of USD 1.5 billion. By 2012, DPP IV inhibitors are expected to more than double its sales to atleast USD 4 billion, capturing 8 % of the overall diabetes market.
Mechanism of Action : The naturally occurring incretin hormones such as GLP-1 (glucagon like peptide-1) and GIP (gastric inhibitory polypeptide) are potent insulinotropic agents playing prominent role in glucose homeostasis. GLP-1 is known to stimulate insulin secretion in response to oral glucose load and inhibits release of glucagon. GLP-1 is rapidly metabolized by the enzyme dipeptidyl peptidase IV, which limits its beneficial action. Extension of the duration of action of GLP-1 has been the focus for the treatment of type II diabetes. Hence, DPP-IV inhibition, by virtue of its ability to preserve GLP-1 levels and stimulate insulin gene expression and biosynthesis, has emerged as one of the targets for the treatment of type 2 diabetes mellitus. DPP-IV inhibitors are known to increase the expression of glucose sensing mechanisms in b-cells of pancreas and promotion of genes involved in the differentiation of b-cells, both of which are of primary importance in the progress of diabetes.”
About the Diabetes market
In 2007, it is estimated that there were 246 million diabetic adult population. Type 2 diabetes mellitus constitutes about 85% to 95% of all diabetes cases in developed countries and accounts for an even higher percentage in developing countries. The epidemic nature of diabetes continues to affect ever-increasing numbers of people around the world.
In 2007, it is estimated that 6.0% of adults aged 20-79 in most countries have diabetes. The Western Pacific Region and the European Region have the highest number of people with diabetes, approximately 67 and 53 million respectively. The highest rate of diabetes prevalence is to be found in the North American region (9.2%) followed by the European Region (8.4%). The global prevalence of diabetes is expected to exceed over 380 million patients by 2025 with an alarming increase in developing countries. Diabetes will no longer be restricted to the developed nations and India is likely to become the diabetes capital of the world.
The global diabetes market is estimated at $24 Bn in 2007 and projected to grow to $ 45 Bn by 2018. It will likely be the leading drug class in metabolic and Cardio Vascular market. Oral anti-diabetics will drive the market growth with a projected share of 70% of the total market or ~S31 Bn in value.
About Glenmark Pharmaceuticals Ltd.:
Glenmark Pharmaceuticals Ltd. (GPL) is a research-driven, global, integrated pharmaceutical company headquartered at Mumbai, India. The company is listed on India’s two premier stock exchanges, the Bombay Stock Exchange (BSE) and the National Stock Exchange (NSE). It employs over 5500 people across its global operations over 85 countries. The Company is a leader in India in the discovery of new molecules and is focused in the areas of inflammation [Asthma/COPD, etc.], and metabolic disorders [Diabetes, Obesity, etc.]. The Company is in the process of creating marketing front-ends for the launch of its proprietary products in the future. Glenmark’s first Asthma/COPD molecule, Oglemilast [GRC 3886], was licensed out to Forest Laboratories and Teijin Pharma Limited for the North American and Japanese markets, respectively, in two landmark deals. Oglemilast is presently undergoing Phase II clinical trials in the US. GRC 6211 has been out-licensed to Eli Lilly & company.
In December 2008, Glenmark bagged the prestigious SCRIP award for the “Best Pharma Company in the World – SME” and the “Best Company in Emerging Markets” at the SCRIP Awards 2008 in London. SCRIP is the leading pharmaceuticals magazine in the world.For more information on GPL, log on to http://www.glenmarkpharma.com/
SOURCE: Glenmark Pharmaceuticals Limited |
