Metformin Extended Release — DepoMed

Abstract

Metformin extended release [Glumetza™, metformin hydrochloride, metformin gastric retention, metformin GR™] is a proprietary once-a-day formulation of metformin hydrochloride under development with DepoMed for the treatment of diabetes.

In May 2002, DepoMed licensed manufacturing and marketing rights for its proprietary formulation of metformin extended release (500mg dose) to Biovail Corporation for the US (including Puerto Rico) and Canada. Under the terms of the agreement, Biovail would pay a $25 million milestone fee upon approval and also customary royalties on the net sales in the US and Canada. Biovail also agreed to acquire approximately 2.4 million of additionally issued DepoMed shares for $12.3 million. Biovail has subsequently developed a 1000mg dose of metformin extended release. In April 2004, Depomed and Biovail amended their original license agreement of May 2002. Under the terms of the amended agreement, Depomed will receive royalties on sales of Biovail’s 1000mg tablet in the US and Canada. In turn, Biovail acquired access to Depomed’s clinical data for the metformin 500mg tablet that will be used to accelerate regulatory filings for Biovail’s 1000mg tablet and establish equivalence between the two dosages.[1]

Metformin GR™ is available for partnership in Europe and Asia (Bio-Square- 2004, Basel, Switzerland).

In April 2004, Depomed and Biovail filed an NDA with the US FDA for the once-daily, extended-release formulation of metformin extended release (Glumetza™), 500mg and 1000mg tablets. The 500mg dosage was developed by Depomed using its patented drug delivery GR™ technology, while Biovail developed the metformin 1000mg dose using its proprietary Smartcoat delivery technology.[1]

Depomed completed two double-blind, pivotal, phase III clinical trials with metformin extended release 500mg at 60 sites in the US in more than 1000 patients with type 2 diabetes. In three different dosing regimens, metformin extended release significantly decreased the glycosylated haemoglobin level similarly to that of metformin immediate release. Biovail successfully compared the metformin extended release 1000mg dose with Depomed’s 500mg dose in multiple equivalence studies. In these studies, metformin extended release was well tolerated and demonstrated an excellent safety profile in terms of gastrointestinal adverse events.

The licensee, Biovail, has submitted an application for metformin extended release with Health Canada.[2]

Bristol-Myers Squibb is marketing a proprietary, once-daily extended-release formulation of metformin (Glucophage® XR).

Several companies are developing controlled-release and extended release formulations of metformin.