Two Diabetes Drugs Get Additional Approvals

July 01, 2013

The once-daily glucagonlike peptide (GLP)-1 agonist lixisenatide(Lyxumia, Sanofi), has been approved in Japan for type 2 diabetes patients when diet and exercise do not provide appropriate control, in combination with sulfonylureas, with and without biguanides (eg, metformin), and/or with basal insulin.

Separately, the dipeptidyl peptidase-4 (DPP-4) inhibitor saxagliptin (Onglyza, Bristol-Myers Squibb/AstraZeneca) has received a positive opinion from the European Medicines Agency for an extension to its marketing authorization in the European Union. If approved, which is usually a formality within a couple of months, the product will additionally be officially indicated as monotherapy for adult patients with type 2 diabetes who cannot be controlled by diet and exercise alone and who cannot take metformin, due to contraindications or intolerance.

Both agents fall under the umbrella of GLP-1–based drugs and have recently been the subject of controversy with regard to a possible increased risk of a rare malignancy — pancreatic cancer — associated with their use. However, the latest guidance indicates there is, as yet, no evidence to substantiate this claim.

Also, there had been hope that the DPP-4 inhibitors, at least, would prove to be cardioprotective. Saxagliptin was the first novel diabetes agent to receive US Food and Drug Administration (FDA) approval after the issuance of new guidelines in December 2008, requiring companies to perform CV-outcomes studies with new diabetes drugs. But just last month, top-line results from the CV-outcomes trial with saxagliptin, SAVOR-TIMI 53, showed no superiority of this agent over placebo in reducing a composite cardiovascular end point when added to usual care in patients with type 2 diabetes with either a history of established CVD or multiple CVD risk factors.

The results were a disappointment, as nonrandomized analyses had raised hopes that this class of drugs might have a cardiovascular protective effect. Full results of SAVOR-TIMI 53 will be reported at the European Society of Cardiology (ESC) 2013 Congress in Amsterdam.

Lixisenatide Approved in Japan

Lixisenatide is already approved in the European Union for the treatment of adults with type 2 diabetes mellitus with oral glucose-lowering products and/or basal insulin when these, together with diet and exercise, do not provide adequate glycemic control. It is also available in Mexico and is under consideration by the US FDA.

Other GLP-1 agonists include once-daily liraglutide (Victoza, Novo Nordisk) — considered the "gold standard" — and exenatide (Byetta, AstraZeneca/Bristol-Myers Squibb Alliance), which is now available as a once-weekly injection. Others are in development, including albiglutide, another once-weekly product from GlaxoSmithKline, which has been filed for approval in the United States and Europe.

Saxagliptin Gets Positive Opinion for Monotherapy in European Union

Meanwhile the European Medicine Agency's Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a variation to the terms of the marketing authorization for saxagliptin last week.

The CHMP adopted the new indication of use of saxagliptin in adults with type 2 diabetes as monotherapy in patients for whom metformin is inappropriate due to contraindications or intolerance. Formal European Commission approval should follow, after which the variation to the marketing authorization will be available in all official European Union languages.

Saxagliptin has been approved as both monotherapy and for use in combination with other oral glucose-lowering medications in the United States since 2009. As of last month, Bristol-Myers Squibb/AstraZeneca said saxagliptin has been submitted for regulatory review in 95 countries and is approved in 86 countries. In addition to the United States as well as those countries in the European Union, these include Canada, Mexico, India, Brazil, and China.


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