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Landmark Phase 3 ‘CREDENCE’ study shows significant reduction of risk of renal failure in patients with type 2 diabetes and chronic kidney disease

  • First significant progress in people living with type 2 diabetes and chronic kidney disease research in nearly 20 years1
  • Sodium-glucose co-transporter-2 (SGLT2) inhibitor, canagliflozin (Invokana®) demonstrated significant reduction in risk of renal failure, dialysis or kidney transplantation, and renal or cardiovascular (CV) death in this high-risk population1

CAMBRIDGE, UK, 15 April 2019: Napp has today welcomed the CREDENCE (Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation) study data which successfully demonstrated that canagliflozin reduces the risk of renal and cardiovascular (CV) events and has an acceptable safety profile consistent with previous studies when added to standard of care in subjects with type 2 diabetes.1 The study met its primary endpoint showing that canagliflozin reduced the risk of composite of doubling of serum creatinine, end-stage kidney disease (ESKD) and renal or CV death by 30% [HR: 0.70; 95% CI:0.59 to 0.82; p<0.0001].1 These findings were consistent across the individual components of the primary composite endpoint, as well as across all 15 subgroups tested.1

In addition, the CREDENCE trial achieved several further secondary endpoints which include; canagliflozin reduced the risk of the secondary renal endpoint composite of doubling of serum creatinine, ESKD, and renal death by 34% [HR0.66; 95% CI: 0.53 to 0.81; p<0.0001].1; canagliflozin reduced the risk of major adverse cardiac events (MACE) (composite of non-fatal myocardial infarction, non-fatal stroke and CV death) by 20% [HR: 0.80; CI: 0.67 to 0.95; p=0.0121]; the risk of CV death and hospitalisation for heart failure by 31% [HR: 0.69; 95% CI: 0.57 to 0.83; p=0.0001]; and the risk of hospitalisation for heart failure alone by 39% [HR: 0.61; 95% CI: 0.47 to 0.80; p=0.0003].1 In regard to safety data, the incidence rates of adverse events and serious adverse events were numerically lower for patients treated with canagliflozin as compared to placebo. There were no observed differences in the incidence of lower limb amputations (HR: 1.11; 95% CI: 0.79 to 1.56) or adjudicated fractures (HR: 0.98; 95% CI: 0.70 to 1.37).1

David Wheeler, Professor of Kidney Medicine at University College London, UK and Honorary Consultant Nephrologist at the Royal Free NHS Foundation Trust, University College London, commented:“Kidney disease develops in approximately 40% of people with type 2 diabetes. We have been waiting for new drugs to help us manage these patients for almost 20 years. The exciting results from the CREDENCE study provide renewed optimism for these patients.”

Andrea Brown, spokesperson for the National Kidney Federation, commented: “Effectively managing chronic kidney disease is a rapidly growing challenge for the NHS and we welcome any research that helps improve the management of this debilitating complication of type 2 diabetes. The exciting research from CREDENCE is the first positive dedicated trial of an antidiabetic agent in this area, showing how under-recognised the irreversible impact of chronic kidney disease and type 2 diabetes has been up until now.”

The data from CREDENCE provides an important update regarding slowing the progression of chronic kidney disease for this group of people with type 2 diabetes. The trial, which was stopped early in July 2018 due to a conclusive signal of efficacy in the prevention of the primary endpoint, was conducted in more than 4,400 adults with type 2 diabetes at 659 sites worldwide, including 37 locations across the UK.5,6

In the UK, canagliflozin is indicated for the treatment of adults with insufficiently controlled type 2 diabetes as an adjunct to diet and exercise.7 The initiation dose is 100mg once daily in adults with an eGFR of ≥ 60 mL/min/1.73 m2 and can be increased to 300mg once daily if tighter glycaemic control is needed.7 Canagliflozin should not be initiated if eGFR is < 60 mL/min/1.73m2.7In patients tolerating canagliflozin whose eGFR falls persistently below 60 mL/min/1.73m2 the dose should be adjusted to or maintained at 100mg once daily. Canagliflozin should be stopped if eGFR falls persistently below 45 mL/min/1.73m2.7

There are over 4 million people with type 2 diabetes in the UK, one third of which may go on to develop irreversible chronic kidney disease – at an annual cost to the NHS between £532-927 million.2,3,8 A serious condition, chronic kidney disease as a result of diabetes accounts for 27.5% of new cases of end-stage kidney failure and significantly increases the risk of CV death.9,10,11

“The publication of CREDENCE delivers critical new evidence in the understanding of chronic kidney disease caused by type 2 diabetes. We are extremely proud to support developments like this, that ultimately help to move medicine forward” said Hywel Day, Managaing Director Napp Pharmaceuticals Ltd.

-ENDS-

Notes to editors:

About the CREDENCE clinical trial

The CREDENCE study was the first dedicated outcome trial evaluating renal and CV outcomes in people with type 2 diabetes and chronic kidney disease with a sodium glucose co-transporter 2 (SGLT2) inhibitor. It was a phase 3, randomised, double-blind, event-driven, placebo-controlled, parallel-group, 2 arm multi-centre study of the effects of canagliflozin on renal and CV outcomes in subjects with type 2 diabetes and chronic kidney disease.6 In particular, it compared the efficacy and safety of canagliflozin versus placebo at preventing clinically important kidney and CV outcomes in patients with type 2 diabetes and chronic kidney disease when used in addition to standard of care, including a maximum tolerated daily dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB).6

About canagliflozin

Canagliflozin is a member of a class of drugs known as SGLT2 inhibitors.12 SGLT2 inhibitors contribute to controlling blood glucose levels via the kidney.12,13 As glucose is filtered from the blood into the kidneys, it is reabsorbed back into the bloodstream.13 An important transport carrier in the kidneys for this reabsorption is called sodium glucose co-transporter 2 (SGLT2).12 Canagliflozin selectively inhibits SGLT2, and, as a result, promotes the loss of glucose via the urine, lowering blood glucose levels in adults with type 2 diabetes.13 This mechanism of action is independent of insulin.13

Canagliflozin is approved in the European Union for the treatment of adults with insufficiently controlled type 2 diabetes as an adjunct to diet and exercise, as monotherapy when metformin is considered inappropriate due to intolerance or contraindications and in addition to other medicinal products for the treatment of diabetes.7,13 Approval was based on a comprehensive global Phase 3 clinical trial programme.7,13,14

About type 2 diabetes

Type 2 diabetes is caused by long-term high levels of sugar (glucose) in the blood.15 Type 2 diabetes is one of the most common long-term health conditions in the UK and typically occurs in older and overweight patients, though it is now being seen in ever-younger patients.­15,16 It is caused by a combination of sedentary lifestyle, unhealthy diet and/or genetic factors.15,16A number of factors can increase the risk of developing type 2 diabetes, including obesity.15,16 Obesity, specifically excess abdominal fat, can make the body less sensitive to insulin, causing a resistance by disrupting the function of insulin responsive cells and therefore the cells’ ability to respond to insulin, leading to higher blood sugar levels (hyperglycaemia).15,16

If not well controlled, type 2 diabetes can lead to long-term complicationssuch as; heart disease, stroke, kidney damage (nephropathy), eye disease (retinopathy) and peripheral nerve damage (neuropathy).4,16

About Napp Pharmaceuticals Ltd

Napp Pharmaceuticals Limited is a UK pharmaceutical company established in the 1920’s and based in the heart of the Cambridge science community. Focused principally in the areas of diabetes, respiratory, cancer, arthritis and gastroenterology, we have worked side by side with the NHS since its inception. As the UK healthcare environment has evolved, so has Napp, ensuring we have the right expertise to mirror what the NHS needs from us, understanding NHS priorities and what influences and drives decision-making. 

We are part of a worldwide network of independent companies, which gives us the flexibility to make locally driven decisions quickly. We have developed our working practices to ensure we can be agile, and act fast and efficiently, in order to help our partners deliver sustainable healthcare solutions that ultimately improve patient outcomes. We aim to bring value-added medicines to the NHS by building effective partnerships. This is innate in the way we work because we are a partnership-based organisation, placing it at the heart of everything we do and every relationship, from our wholesale distributors to NHS decision-makers.

We are extremely proud of our heritage in partnership working, which is centred around building and developing mutually beneficial, enduring partnerships that are open and based on respect – this is how we have built our reputation as a partner of choice.

UK/INV-19101   |  April 2019

For more information please contact or visit:

Diana Evans, Head of Communications

Email: diana.evans@napp.co.uk

Tel: +44 (0)1223 393191

 

Nappwww.napp.co.uk

National Kidney Federation: https://www.kidney.org.uk

 

Tatiana Allan

Cello Health Communications

Email: tallan@ch-corporateaffairs.co.uk

Phone: +44 203 434 1012

 

References:

  1. Perkovic, V. et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019 DOI: 10.1056/NEJMoa1811744
  2. Diabetes UK. Us, diabetes and a lot of facts and stats. Available at: https://www.diabetes.org.uk/resources-s3/2019-02/1362B_Facts%20and%20stats%20Update%20Jan%202019_LOW%20RES_EXTERNAL.pdf. Last accessed: April 2019.
  3. Diabetes UK. 2019. Kidney disease (nephropathy). Available at: https://www.diabetes.org.uk/guide-to-diabetes/complications/kidneys_nephropathy. Last accessed: April 2019.
  4. Update to International Diabetes Federation, 2016, Complications of Diabetes [Online] Available at: https://www.idf.org/aboutdiabetes/what-is-diabetes/complications.htmlLast accessed April 2019.
  5. Phase 3 CREDENCE Renal Outcomes Trial of INVOKANA® (canagliflozin) is Being Stopped Early for Positive Efficacy Findings. Available at: https://www.janssen.com/phase-3-credence-renal-outcomes-trial-invokanar-canagliflozin-being-stopped-early-positive-efficacy. Last accessed April 2019.
  1. gov. 2014. Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy (CREDENCE). Available at: https://clinicaltrials.gov/ct2/show/NCT02065791. Last accessed: April 2019.
  2. 2018. SmPC. Invokana 100 mg and 300 mg film-coated tablets. Available at: https://www.medicines.org.uk/emc/product/8855#INDICATIONS. Last accessed: April 2019.
  3. Gordois, A., et al. The health care costs of diabetic nephropathy in the United States and the United Kingdom. J Diabetes Complications. 2004 Jan-Feb;18(1):18-26.
  4. Kidney Care UK. Diabetes. Available at: https://www.kidneycareuk.org/about-kidney-health/conditions/diabetes/. Last accessed: April 2019.
  5. Pálsson, R and Patel, UD. Cardiovascular Complications of Diabetic Kidney Disease. Adv Chronic Kidney Dis. 2014 May; 21(3): 273–280.
  6. Afkarian, M., et al. Kidney Disease and Increased Mortality Risk in Type 2 Diabetes. J Am Soc Nephrol. 2013;24: 302–308. doi: 10.1681/ASN.2012070718.
  7. co.uk. 2017. Invokana (Canagliflozin). Available at: http://www.diabetes.co.uk/diabetes-medication/invokana-canagliflozin.html. Last Accessed: April 2019.
  8. European Medicines Agency. 2013. EPAR Summary for the Public: Invokana canagliflozin. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/002649/WC500156455.pdf. Last Accessed: April 2019.
  9. Canagliflozin Phase 3 Clinical Trial Programme. Available at: https://www.janssen.com/emea/sites/www_janssen_com_emea/files/canagliflozin_phase_3_backgrounder_2014_08_13_final.pdf. Last accessed: April 2019.
  10. co.uk. 2019. Type 2 Diabetes. Available at: http://www.diabetes.co.uk/type2-diabetes.html. Last accessed: April 2019.
  11. co.uk. 2019. Diabetes and obesity. Available at: https://www.diabetes.co.uk/diabetes-and-obesity.html. Last accessed: April 2019.
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