Boehringer Ingelheim and Lilly present full results of Trajenta®’s CARMELINA® cardiovascular outcome trial

  • Trajenta® demonstrated a similar long-term cardiovascular and kidney safety profile compared to placebo in adults with type 2 diabetes1
  • The results of CARMELINA® were presented at the 54th EASD Annual Meeting today

Ingelheim, Germany and Indianapolis, US, 4 October 2018 – Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) today presented the full results of the long-term cardiovascular outcome trial, CARMELINA®, which studied the impact of Trajenta® (linagliptin) on cardiovascular and kidney safety in adults with type 2 diabetes at high risk for heart and/or kidney disease.1,2 The study met its primary endpoint,* with linagliptin demonstrating a similar cardiovascular safety profile compared to placebo when added to standard of care.1 CARMELINA® also included a key secondary composite endpoint,† showing a similar kidney safety profile compared to placebo.1

The overall safety profile of linagliptin in CARMELINA® was consistent with previous data and no new safety signals were observed.1 CARMELINA® also showed a similar rate of hospitalisation for heart failure for linagliptin compared to placebo.1

The full results were presented at the 54th European Association for the Study of Diabetes (EASD) Annual Meeting in Berlin, Germany.

“Heart disease is a major complication and the leading cause of death for people living with type 2 diabetes. CARMELINA® adds important new evidence for type 2 diabetes patients at high risk of heart and/or kidney disease, a population that has been underrepresented in other cardiovascular outcome trials, but whom we see in our daily practice. The trial confirmed that linagliptin can be used with confidence in this patient population,” commented Bernard Zinman, M.D., Professor in the Department of Medicine, University of Toronto and Senior Scientist at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada.

In CARMELINA®, cardiovascular events that contributed to the primary endpoint* occurred in 12.4 percent (434 people) of the linagliptin group compared to 12.1 percent (420 people) in the placebo group, demonstrating a similar long-term cardiovascular safety profile in adults with type 2 diabetes.1 Linagliptin also showed a similar long-term kidney safety profile compared to placebo. This was demonstrated on the composite endpoint reflecting declining kidney function† occurring in 9.4 percent (327 people) of the linagliptin group compared to 8.8 percent (306 people) of the placebo group.1

An increase in the risk of hospitalisation for heart failure has been observed in some other cardiovascular outcome trials in diabetes.3,4 In CARMELINA®, this endpoint was pre-specified and assessed thoroughly via adjudication. Hospitalisation for heart failure occurred in 6 percent (209 people) of the linagliptin group compared to 6.5 percent (226) of the placebo group.1 “These results are particularly meaningful given the patient population in CARMELINA, including those most vulnerable to developing heart failure,” said Waheed Jamal, MD, Corporate Vice President and Head of CardioMetabolic Medicine, Boehringer Ingelheim.

* Primary endpoint defined as time to first occurrence of the 3-P MACE (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) Key secondary endpoint defined as time to first occurrence of sustained end stage kidney disease (ESKD), death due to kidney disease, or a sustained decrease in eGFR from baseline of ≥40 percent compared to placebo Assessed by an independent clinical event committee in a blinded way

“While many guidelines5,6 now recognise the importance of choosing a diabetes treatment with a proven benefit on reducing cardiovascular risk and mortality in people with type 2 diabetes and heart disease, there remains a need for additional glucose-lowering options,” Waheed Jamal pointed out. “CARMELINA® reinforces confidence in linagliptin as an effective and well-tolerated treatment, with a simple dosing regimen for adults with type 2 diabetes.”

“We have created a unique cardiovascular outcome trial programme for linagliptin with two trials — CARMELINA®, whose results are released today, as well as CAROLINA®, which will report initial results in the near future,” added Jeff Emmick, MD, PhD, Vice President, Product Development, Lilly Diabetes. “This programme will provide clinical data on the long-term safety profile of linagliptin in a broad range of adults with type 2 diabetes, which reflects patients that doctors see in their daily practice.7

About CARMELINA®
CARMELINA® is a multi-national, randomised, double-blind, placebo-controlled clinical trial that involved 6,979 adults with type 2 diabetes from 27 countries at more than 600 sites observed for a median duration of 2.2 years.2,8 The study was designed to assess the effect of linagliptin (5mg once daily) compared to placebo (both added to standard of care) on cardiovascular outcomes in adults with type 2 diabetes and high cardiovascular risk, the majority of whom also had kidney disease.2,8 This population of people with high risk of cardiovascular and/or kidney disease reflects patients that doctors see in their daily practice.7 Standard of care included both glucose lowering agents and cardiovascular drugs (including antihypertensive and lipid lowering agents).

CARMELINA® was led by an academic trial steering committee and the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance. Compared to other recently reported outcome trials of dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes, CARMELINA® included the highest number of patients with impaired kidney function.§

To learn more about CARMELINA®, please visit: https://www.carmelinatrial.com/

§ Glomerular filtration rate below 30 mL/min/m2

About Trajenta® (linagliptin)
Trajenta® is a one dose, once daily DPP-4-inhibitor that provides significant efficacy in the reduction of blood sugar levels for adults with type 2 diabetes. It can be prescribed for adult patients with type 2 diabetes regardless of age, disease duration, ethnicity, body mass index (BMI), liver and kidney function.9 Trajenta® has the lowest kidney excretion rate of all DPP-4 inhibitors.9-13

About our cardiovascular outcome trials
As cardiovascular disease is a major complication and the leading cause of death in type 2 diabetes,14 cardiovascular safety of all type 2 diabetes treatments is important. Worldwide, most people with type 2 diabetes die of a cardiovascular event.15 In 2015, Boehringer Ingelheim and Eli Lilly and Company announced results from the landmark cardiovascular outcome trial EMPA-REG OUTCOME® with the SGLT2 inhibitor empagliflozin.16,17

CARMELINA® is one of two cardiovascular outcome trials with the DPP-4 inhibitor linagliptin. CAROLINA®,18 will be the first DPP-4 inhibitor cardiovascular outcome trial to compare commonly used second line treatments — linagliptin and the sulphonylurea glimepiride. This trial includes adults with relatively early type 2 diabetes and increased cardiovascular risk or established complications, with less than optimised blood sugar control. The majority did not yet have heart and kidney disease. The study will report initial results in the near future. CARMELINA® and CAROLINA® will provide clinical data on the long-term safety profile of linagliptin in a broad range of adults with type 2 diabetes, which reflects patients that doctors see in their daily practice.7

Boehringer Ingelheim and Eli Lilly and Company
In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an alliance in diabetes that centres on compounds representing several of the largest diabetes treatment classes. The alliance leverages the strengths of two of the world’s leading pharmaceutical companies. By joining forces, the companies demonstrate commitment in the care of people with diabetes and stand together to focus on patient needs. Depending on geographies, the companies either co-promote or separately promote the respective molecules each contributed to the alliance.

Boehringer Ingelheim
Improving the health and quality of life of patients is the goal of the research-driven pharmaceutical company, Boehringer Ingelheim. The focus in doing so is on diseases for which no satisfactory treatment option exists to date. The company therefore concentrates on developing innovative therapies that can extend patients’ lives. In animal health, Boehringer Ingelheim stands for advanced prevention.

Family-owned since it was established in 1885, Boehringer Ingelheim is one of the pharmaceutical industry’s top 20 companies. Some 50,000 employees create value through innovation daily for the three business areas human pharmaceuticals, animal health and biopharmaceuticals. In 2017, Boehringer Ingelheim achieved net sales of nearly 18.1 billion euros. R&D expenditure, exceeding three billion euros, corresponded to 17.0 per cent of net sales.

As a family-owned company, Boehringer Ingelheim plans in generations and focuses on long-term success, rather than short-term profit. The company therefore aims at organic growth from its own resources with simultaneous openness to partnerships and strategic alliances in research. In everything it does, Boehringer Ingelheim naturally adopts responsibility towards mankind and the environment.

More information about Boehringer Ingelheim can be found on www.boehringer-ingelheim.com or in our annual report: http://annualreport.boehringer-ingelheim.com

About Lilly Diabetes
Lilly has been a global leader in diabetes care since 1923, when we introduced the world's first commercial insulin. Today we are building upon this heritage by working to meet the diverse needs of people with diabetes and those who care for them. Through research and collaboration, a wide range of therapies and a continued determination to provide real solutions—from medicines to support programs and more—we strive to make life better for all those affected by diabetes around the world. For more information, visit www.lillydiabetes.com.

About Eli Lilly and Company
Lilly is a global healthcare leader that unites caring with discovery to make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at www.lilly.com and newsroom.lilly.com/social-channels.

Intended audiences
This press release is issued from Boehringer Ingelheim Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where Boehringer Ingelheim and Eli Lilly and Company do business.

This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Trajenta® and its safety profile, and reflects Lilly's current belief. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of development and commercialization. Among other things, there can be no guarantee that future study results will be consistent with the results to date or that Trajenta® will receive additional regulatory approvals. For further discussion of these and other risks and uncertainties, see Lilly's most recent Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.

Boehringer Ingelheim and Lilly present full results of Trajenta®’s CARMELINA® cardiovascular outcome trial.

CONTACT:
Katharina Opitz
Product Communication
Boehringer Ingelheim
Email: press@boehringer-ingelheim.com
Phone: +49 (6132) 77 2012
Gregory Andrew Kueterman
Director of Communications
Lilly Diabetes and Lilly USA
Email: kueterman_gregory_andrew@lilly.com
Phone: +1 (317) 432-5195

REFERENCES
1. Rosenstock J, et al. Cardiovascular and Renal Microvascular Outcome Study with Linagliptin in Patients with Type 2 Diabetes Mellitus (CARMELINA®). Oral presentation at the 54thAnnual Meeting of the European Association for the Study of Diabetes (EASD), Thursday, 4 October 2018, 17:15 - 18:15, Langerhans Hall, Berlin Germany.
2. ClinicalTrials.Gov. Cardiovascular and renal microvascular outcome study with linagliptin in patients with type 2 diabetes mellitus at high vascular risk. Available from: https://clinicaltrials.gov/ct2/show/NCT01897532?term=NCT01897532&rank=1. Accessed: September 2018.
3. Green JB, et al. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2015;373(3):232-42.
4. Scirica BM, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369(14):1317-26.
5. Piepoli MF, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts). Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016;37(29):2315-81.
6. Introduction: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S1-S2.
7. Boehringer Ingelheim and Eli Lilly and Company. Data on file.
8. Rosenstock J, et al. Rationale, design, and baseline characteristics of the CArdiovascular safety and Renal Microvascular outcomE study with LINAgliptin (CARMELINA®): a randomized, double-blind, placebo-controlled clinical trial in patients with type 2 diabetes and high cardio-renal risk. Cardiovasc Diabetol. 2018;17(1):39.
9. European Medicines Agency. Trajenta® (linagliptin) tablets. EMA Summary of Product Characteristics. Updated August 2017. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002110/WC500115745.pdf. Accessed: September 2018.
10. European Medicines Agency. Onglyza® (saxagliptin) tablets. EMA Summary of Product Characteristics. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001039/WC500044316.pdf. Last updated: July 2016. Accessed: September 2018.
11. European Medicines Agency. Vipidia® (alogliptin) tablets. EMA Summary of Product Characteristics. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002182/WC500152271.pdf. Last updated: Janaury 2015. Accessed: September 2018.
12. European Medicines Agency. Januvia® (sitagliptin) tablets. EMA Summary of Product Characteristics. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000722/WC500039054.pdf. Last updated: August 2017. Accessed: September 2018.
13. European Medicines Agency. Galvus® (vildagliptin) tablets. EMA Summary of Product Characteristics. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000771/WC500020327.pdf. Last updated: June 2017. Accessed: September 2018.
14. World Heart Federation. Cardiovascular Disease Risk Factors. Available from: https://www.world-heart-federation.org/resources/risk-factors/. Accessed: September 2018.
15. Morrish NJ, et al. Mortality and causes of death in the WHO Multinational Study of Vascular Disease in Diabetes. Diabetologia. 2001;44 Suppl 2:S14-21.
16. Zinman B, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-28.
17. Jardiance® (Full Prescribing Information). U.S.; Boehringer Ingelheim Pharmaceuticals, Inc; 2017.
18. ClinicalTrials.Gov. CARdiovascular Outcome study of LINAgliptin versus Glimepiride in patients with Type 2 diabetes. Available from: https://clinicaltrials.gov/ct2/show/NCT01243424. Accessed: September 2018.
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