Zydus Cadila becomes second Indian pharma with US IND for GK activator in diabetes

Zydus Cadila, one of India’s leading healthcare companies announced that it has received an IND approval from the US FDA for ZYGK1, an orally administered small molecule glucokinase activator for Type 2 diabetes. The move reinforces Zydus' transition from its heavy dependence on generics to its ambitions as a research-led company. It also makes Zydus the second Indian company exploring the glucokinase activation space, alongside Advinus.

Speaking on the new development, Pankaj R. Patel, Chairman and Managing Director of Zydus Cadila, said, “We have been building a promising pipeline of new molecular entities at the Zydus Research Centre and with each step forward, we are moving closer to our goal of becoming a research driven pharma major. We believe that these sustained efforts will help us address unmet healthcare needs in the focus areas of metabolic disorders and cardiovascular diseases.” The molecule was designed and developed at the Zydus Research Centre in Ahmedabad.

In patients with Type 2 diabetes, reduced glucokinase activity in the pancreas and the liver results in a lowered insulin release. Zydus hopes that the phase I trial of ZYGK1 will show that activating glucokinase addresses this deficiency.

In multiple preclinical models of Type 2 diabetes, ZYGK1 was found to be effective in controlling both fasting and non-fasting blood glucose. ZYGK1 showed very good safety profile in preclinical studies. Activating GK with small molecules such as ZYGK1 lower blood glucose levels by enhancing the ability of the pancreas to sense glucose, which leads to increased insulin production. Simultaneously, glucokinase activators increase the net uptake of blood glucose by the liver. Glucokinase activators, such as ZYGK1, represent a promising new class of drugs for the treatment of Type 2 diabetes.

Zydus now has several NMEs in clinical development in metabolic disease: ZYH1, for dyslipidemia is in Phase III; ZYOG1, an oral GLP-1 agonist for diabetes, ZYH7, for dyslipidemia and ZYH2, for diabetes have completed Phase I trials; ZYO1, for obesity and related disorders, ZYD1, a GLP-1 agonist to treat diabetes and ZYT1, a TR-beta agonist for treating dyslipidemia are still in Phase I.

Table 1. Glucokinase activators in type 2 diabetes development: Source TrialTrove

Company	Compound	Phase
Eli Lilly	LY-2608204	I
Advinus	GKM-001	I
Zydus Cadila	ZYGK-1	I
Forest Laboratories, TransTech Pharma	TTP-399	II
AstraZeneca	AZD1656	II

Author	Name	Anju Ghangurde
	Email	[email protected]
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