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Boehringer Ingelheim and Eli Lilly and Company's DPP-4 inhibitor today received a positive opinion from the European Medicines Agency's (EMA) medicinal committee
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Ingelheim, Germany, 24 June, 2011 – 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®) 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 type 2 diabetes patients in Europe.
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.1 Linagliptin is also recommended for approval in combination with metformin and metformin + sulphonylurea.1 Data shows that linagliptin reduces haemoglobin A1c (HbA1c) levels by a mean of -0.6 to -0.7 percent2,3 (compared to placebo). HbA1c 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. "Studies show that linagliptin is efficacious with a favourable safety and tolerability profile. It is also primarily excreted unmetabolised via bile and gut, meaning no dose adjustment is needed in patients with declining kidney or liver function. Therefore, this will be the first DPP-4 inhibitor available at one dose for all patients".
Linagliptin 5 mg received a positive opinion based on a clinical trial programme which involved approximately 6,000 adults with type 2 diabetes. Included in the programme were placebo-controlled studies evaluating linagliptin as monotherapy4 and in combination with the commonly prescribed oral antihyperglycaemic medications metformin and / or sulphonylurea.2,5-6 In two monotherapy studies, linagliptin showed a statistically significant mean difference in HbA1c from placebo of -0.6 to -0.7 percent.3-4 In patients who were not adequately controlled on metformin or metformin plus sulphonylurea, the addition of linagliptin also resulted in a statistically significant mean difference in HbA1c from placebo of -0.6 percent. 2,5
In a study comparing the efficacy and safety of the addition of linagliptin 5 mg or glimepiride (mean dose 3 mg) in patients with inadequate glycaemic control on metformin monotherapy, mean reductions in HbA1c were -0.16% with linagliptin (mean baseline HbA1c 7.69%) and -0.36% with glimepiride (mean baseline HbA1c 7.69%) with a mean treatment difference of 0.20% (97.5% CI: 0.09, 0.299). The incidence of hypoglycaemia in the linagliptin group (7.5%) was significantly lower than that in the glimepiride group (36.1%). Patients treated with linagliptin exhibited a significant mean decrease from baseline in body weight compared to a significant weight gain in patients administered glimepiride (-1.39 vs +1.29 kg).
"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 US 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 patients with type 2 diabetes."
Linagliptin is an inhibitor of the enzyme DPP-4 (Dipeptidyl peptidase-4) an enzyme which is involved in the inactivation of the incretin hormones GLP-1 and GIP (glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide). Linagliptin glucose-dependently increases insulin secretion and lowers glucagon secretion thus resulting in an overall improvement in the glucose homoeostasis.1
Treatment with linagliptin produced significant reductions in fasting plasma glucose (FPG) compared to placebo, when used as monotherapy4 and in combination with metformin and/or sulphonylurea.2,5 Treatment with linagliptin produced significant reductions in two-hour post-prandial glucose (PPG) levels compared with placebo when used in combination with metformin. FPG is used to determine glucose levels in a fasting state (usually upon wakening in the morning), and PPG is used to determine glucose levels after meals (usually two hours after eating).
No dose adjustment for linagliptin is required even for patients with renal impairment.1 In controlled studies, change from baseline in body weight did not differ significantly between groups when linagliptin was administered as monotherapy4, in combination with metformin2 or in combination with metformin plus sulphonylurea.5 Patients treated with linagliptin exhibited a significant mean decrease from baseline body weight compared to a significant weight gain in patients administered sulphonylurea (-1.39 kg vs. +1.29 kg. p<0.0001).
An estimated 285 million people worldwide have diabetes.7 Type 2 diabetes is the most common type, accounting for an estimated 90 percent of all diabetes cases.8 Diabetes is a chronic disease that occurs when the body either does not properly produce, or use, the hormone insulin.9
Boehringer Ingelheim and Eli Lilly and Company
In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an alliance in the field of diabetes that centres on four pipeline compounds representing several of the largest treatment classes. This alliance leverages the companies’ strengths as two of the world’s leading pharmaceutical companies, combining Boehringer Ingelheim’s solid track record of research-driven innovation and Lilly’s innovative research, experience, and pioneering history in diabetes. By joining forces, the companies demonstrate commitment in the care of patients with diabetes and stand together to focus on patient needs. Find out more about the alliance at www.boehringer-ingelheim.com or www.lilly.com.
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 42,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavours.
In 2010, Boehringer Ingelheim posted net sales of about 12.6 billion euro while spending almost 24 percent of net sales in its largest business segment Prescription Medicines on research and development.
About Eli Lilly and Company
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, IN, Lilly provides answers – through medicines and information – for some of the world's most urgent medical needs. Additional information about Lilly is available at www.lilly.com.
About Lilly Diabetes
For more than 85 years, Lilly has been a worldwide leader in pioneering industry-leading solutions to support people living with and treating diabetes. Lilly introduced the world's first commercial insulin in 1923, and remains at the forefront of medical and delivery device innovation to manage diabetes. Lilly is also committed to providing solutions beyond therapy – practical tools, education, and support programmes to help overcome barriers to success along the diabetes journey. At Lilly, the journeys of each person living with or treating diabetes inspire ours. For more information, visit www.lillydiabetes.com.
This press release contains forward-looking statements about linagliptin tablets for the treatment of type 2 diabetes. It reflects Lilly's current beliefs; however, as with any such undertaking, there are substantial risks and uncertainties in the process of drug development and commercialization. There is no guarantee that future study results and patient experience will be consistent with study findings to date or that linagliptin will be commercially successful. For further discussion of these and other risks and uncertainties, please see Lilly's latest Forms 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.
1Trajenta™ (linagliptin) tablets. EMA Summary of Product Characteristics.
2Taskinen MR, Rosenstock J, Tamminen I, et al: Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Diabetes Obes Metab 2011;13:65-74.
3Del Prato S, Barnett AH, Huisman H, et al: Effect of linagliptin monotherapy on glycaemic control and markers of B-cell function in patients with inadequately controlled type 2 diabetes: a randomised controlled trial. Diabetes Obes Metab 2011;13:193-287.
4Barnett AH, Harper R, Toorawa R, et al: Linagliptin monotherapy improves glycaemic control in type 2 diabetes patients for whom metformin therapy is inappropriate, 46th Annual Meeting of the European Association for the Study of Diabetes. Stockholm, Sweden, 2010, pp Poster 823.
5Owens DR, Swallow R, Woerle HJ, et al: Linagliptin improves glycemic control in type 2 diabetes patients inadequately controlled by metformin and sulfonylurea without weight gain and low risk of hypoglycemia, 70th American Diabetes Association Scientific Sessions. Orlando, Florida, U.S.A., 2010, pp Poster 548-P.
6Lewin AJ, Arvay L, Liu D, et al: Safety and efficacy of linagliptin as add-on therapy to a sulphonylurea in inadequately controlled type 2 diabetes, 46th Annual Meeting of the European Association for the Study of Diabetes. Stockholm, Sweden, 2010, pp Poster 821-P
7International Diabetes Federation: Diabetes prevalence, 2009.
8International Diabetes Federation: www.idf.org, 2010.
9World Health Organization: Fact Sheet No. 312 What is Diabetes?, 2010.