EMA CHMP recommends approval of linagliptin for type 2 diabetes

Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) today received a positive opinion from the European Medicines Agency's (EMA) medicinal committee recommending approval of linagliptin, 5 mg, film-coated tablets (to be marketed under the trade name Trajenta® in Europe) for the treatment of adults with type 2 diabetes. If adopted by the European Commission, linagliptin will be the only DPP-4 inhibitor approved at one dosage strength for patients with type 2 diabetes in Europe.  Linagliptin, 5 mg, is marketed under the trade name Tradjenta™ (linagliptin) tablets in the U.S. and was approved by the U.S. Food and Drug Administration (FDA) in May 2011 to be used along with diet and exercise to lower blood sugar in adults with type 2 diabetes.  Linagliptin should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis (increased ketones in the blood or urine). It has not been studied in combination with insulin.

The Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of linagliptin as monotherapy in patients inadequately controlled by diet and exercise alone and for whom metformin is inappropriate due to intolerance, or contraindicated due to renal impairment. Linagliptin is also recommended for approval in combination with metformin and metformin plus sulfonylurea. Data showed linagliptin plus metformin reduced hemoglobin A1C (HbA1C or A1C) levels by a mean of 0.6 to 0.7 percent (compared to placebo). A1C is measured in people with diabetes to provide an index of blood glucose control for the previous two to three months. It is used as a marker to determine the efficacy of glucose-lowering therapies.

"This will be an important step forward in the management of type 2 diabetes in Europe," said Prof. Anthony Barnett, clinical director, Department of Diabetes and Endocrinology, University of Birmingham and Heart of England NHS, UK. "Of note, linagliptin is primarily excreted via the bile and gut, meaning no dose adjustment is recommended in patients with kidney or liver impairment. Therefore, this will be the first DPP-4 inhibitor available at one dose for all adult patients with type 2 diabetes."

Linagliptin received a positive opinion based on a clinical trial program which involved approximately 4,000 adults with type 2 diabetes. Included in the program were placebo-controlled studies evaluating linagliptin as monotherapy and in combination with the commonly prescribed oral antihyperglycemic medications, metformin and/or sulfonylurea.  In two monotherapy studies, linagliptin showed a statistically significant mean difference in A1C from placebo of -0.6 to -0.7 percent. In patients who were not adequately controlled on metformin or metformin plus sulfonylurea, the addition of linagliptin also resulted in a statistically significant mean difference in A1C from placebo of -0.6 percent.

"Type 2 diabetes is increasing at an alarming rate worldwide. We are proud that we may soon have the opportunity to offer a new treatment option from our own Boehringer Ingelheim research labs to the millions of European patients with type 2 diabetes whose blood glucose is not adequately controlled," said Prof. Klaus Dugi, corporate senior vice president medicine, Boehringer Ingelheim.

The CHMP positive opinion for linagliptin marks another regulatory milestone for the Boehringer Ingelheim and Eli Lilly and Company worldwide diabetes alliance, which was formed in January 2011. Linagliptin received approval for use in the U.S. in May 2011.

"We are extremely pleased by the CHMP positive recommendation for approval of linagliptin in Europe," said Enrique Conterno, president of Lilly Diabetes. "Based on our comprehensive studies and the CHMP's positive recommendation, we believe linagliptin can be an important new treatment option for adult patients with type 2 diabetes."