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Independent Data Monitoring Committee (IDMC) stops CREDENCE Phase III trial early, following positive efficacy findings of Invokana (canagliflozin) in people with type 2 diabetes and chronic kidney disease (CKD)[1]
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5 million people in the UK are diagnosed with type 2 diabetes, 40% of which may develop chronic kidney disease at a cost of £8.8 billion to the NHS[2],[3],[4]
Cambridge, UK: 17 July 2018. As the exclusive UK distributor of Invokana (canagliflozin) and Janssen’s partner of choice in diabetes, Napp welcomes the announcement from the Janssen Pharmaceutical Companies of Johnson & Johnson, that the Phase III CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) clinical trial has been stopped early based on a decision from the IDMC.[1],[5] The recommendation is based on demonstration of efficacy as the trial achieved pre-specified criteria for the primary composite end points.[1]
CREDENCE is the first dedicated renal outcomes trial in patients with CKD and type 2 diabetes, which reviewed the efficacy and safety of Invokana (canagliflozin) versus placebo when used in addition to standard of care.[1] The trial assessed efficacy and safety by evaluating the risk and reduction of time to dialysis or kidney transplantation, doubling of serum creatinine, and renal or cardiovascular death.[1]
“3 million people are currently living with CKD in the UK, a large proportion of which have diabetes, and many patients progress to requiring treatments such as dialysis, which can cause a significant negative impact on a patient’s day to day life, and kidney transplants,” said Professor Philip Kalra, Consultant Nephrologist at Salford Royal and the University of Manchester. “We are excited by this positive announcement, and the demonstration of Invokana’s potential to treat patients with type 2 diabetes and CKD and we look forward to seeing the beneficial changes this could have on patients’ health.”
Approximately 3.5 million people in the UK are diagnosed with type 2 diabetes, and 3 million are currently living with CKD, a progressive condition that impacts a person’s overall health and wellbeing.[1],[2],[6] Nearly 40% of people living with type 1 and 2 diabetes will develop CKD or kidney problems during their lifetime, which can result in patients requiring renal treatments such as dialysis or kidney transplants.[3],[7] With the current cost to the NHS of direct patient care for people living with type 2 diabetes and its comorbidities estimated at £8.8 billion annually, and the cost of CKD at £1.45 billion per year, this is particularly exciting news for the NHS at a time when the health service is under ever increasing financial pressure to provide sustainable healthcare options.[4],[8]
“This announcement highlights canagliflozin as a possible kidney protective treatment option for people living with type 2 diabetes and CKD, a condition that can be complex and difficult to manage. Canagliflozin is already helping to manage the early treatment and control of type 2 diabetes, and although we cannot comment on the data from the trial at this time, we look forward to seeing the full trial results and the positive impact this could have on patients in the UK,” said Paul Schofield, Medical Director at Napp Pharmaceuticals Ltd.
For further information and questions on the data specifically, please contact Janssen directly, who conducted the study.
Notes to editors:
About Invokana (canagliflozin)
Invokana is a member of a class of drugs known as sodium glucose co-transporter 2 (SGLT2) inhibitors.[9]
SGLT2 inhibitors contribute to controlling blood glucose levels via the kidney.[9] As glucose is filtered from the blood into the kidneys, it is reabsorbed back into the bloodstream.[9],[10] SGLT2is are an important transport carrier in the kidneys for this reabsorption.[9] 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.[10],[11] This mechanism of action is independent of insulin.[11]
In November 2013, the European Commission approved Invokana in the European Union for the treatment of adults with type 2 diabetes mellitus, to improve glycaemic (i.e blood sugar) control.[10],[12]
Canagliflozin has been studied as monotherapy and in combination with other type 2 diabetes therapies including insulin.[12] It is recommended to start canagliflozin at 100mg once daily and if tolerated this can be increased to 300mg for tighter blood glucose control in patients with adequate kidney function (eGFR > 60ml/min/1.73m2).[12] The Phase III programme evaluated the safety and efficacy of canagliflozin across the spectrum of type 2 diabetes and included placebo and active comparator-controlled studies.[10],[13] Three studies have compared canagliflozin to current standard treatments; two of which compared canagliflozin to sitagliptin (Januvia®) which showed non-inferior efficacy measured by HbA1c reduction (a marker of blood glucose control) at the 100mg dose, and a superior HbA1c reduction at the 300mg once daily dose, together with a similar tolerability profile.[10],[14],[15] The third study compared canagliflozin to glimepiride (Amaryl®) as dual therapy with metformin which showed a lower risk of hypoglycaemia.[16] The Phase III programme also included two large studies in special populations: patients over age 55 with type 2 diabetes and patients with type 2 diabetes who were considered to be at high risk for cardiovascular disease.[17],[18]
Common adverse drug reactions associated with the use of Invokana include urinary tract infections (UTIs), hypoglycaemia, nausea, constipation, thirst, polyuria or pollakiuria, vulvovaginal candidiasis, balanitis or balanoposthitis, dyslipidemia and increased haematocrit.[12]
About Type 2 Diabetes
Type 2 diabetes is a chronic condition that results in the body being unable to metabolise sugar (glucose).[19] A number of factors can increase the risk of developing type 2 diabetes, including obesity.[19],[20] 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 (hyperglycemia).[19],[20] If left uncontrolled, type 2 diabetes can lead to long-term complications such as heart attack, stroke, kidney damage (nephropathy), eye disease (retinopathy) and peripheral nerve damage (neuropathy).[19]
About Napp Pharmaceuticals Limited
Napp Pharmaceuticals Limited is a UK pharmaceutical company based in the heart of the Cambridge science community, and part of a worldwide network of independently associated companies across 48 countries. Napp has grown up with the NHS, providing innovative medicines to patients in the UK since the 1920s. Napp is committed to improving patient outcomes and ensuring the sustainability of healthcare. At Napp, we are proud of our heritage, which began in the treatment of chronic pain and has expanded into respiratory medicine, diabetes, oncology and inflammatory disorders.
For more information, please visit: www.napp.co.uk
For further information, please contact:
Hanna Wikström, Communications Lead, Napp Pharmaceuticals Ltd
hanna.wikstrom@napp.co.uk / T: +44 (0)1223 424 444
References:
[1] Johnson & Johnson. 2018. Phase 3 CREDENCE Renal Outcomes Trial of INVOKANA® (canagliflozin) is Being Stopped Early for Positive Efficacy Findings. Available at: https://www.jnj.com/phase-3-credence-renal-outcomes-trial-of-invokana-canagliflozin-is-being-stopped-early-for-positive-efficacy-findings. Last Accessed: July 2018.
[2] Diabetes.co.uk. 2018. Diabetes Prevalence. Available at: https://www.diabetes.co.uk/diabetes-prevalence.html. Last Accessed: July 2018.
[3] Diabetes UK. 2018. Diabetes and kidney care. Available at: https://www.diabetes.org.uk/professionals/resources/shared-practice/kidney-care. Last Accessed: July 2018.
[4] NHS Choices. 2012. Diabetes: cases and costs predicted to rise. Available at: https://www.nhs.uk/news/diabetes/diabetes-cases-and-costs-predicted-to-rise/. Last Accessed: July 2018.
[5] Napp Pharmaceuticals Limited. 2017. Napp secures appointment as exclusive distributor of Invokana▼® in the UK. Available at: http://napp.co.uk/archives/secondary_news/napp-secures-appointment-as-exclusive-distributor-of-invokana%E2%96%BC-in-the-uk. Last Accessed: July 2018.
[6] Kidney Care UK. 2018. Facts and Stats. A range of useful facts and stats about kidneys. Available at: https://www.kidneycareuk.org/news-and-campaigns/facts-and-stats/. Last Accessed: July 2018.
[7] Kidney Research UK. 2017. Diabetes Summary. Available at: https://www.kidneyresearchuk.org/health-information/diabetes. Last Accessed: July 2018.
[8] NHS Kidney Care. 2012. Chronic Kidney Disease in England: The Human and Financial Costs. Available at: https://www.england.nhs.uk/improvement-hub/wp-content/uploads/sites/44/2017/11/Chronic-Kidney-Disease-in-England-The-Human-and-Financial-Cost.pdf. Last Accessed: July 2018.
[9] Diabetes.co.uk. 2017. Invokana (Canagliflozin). Available at: http://www.diabetes.co.uk/diabetes-medication/invokana-canagliflozin.html. Last Accessed: July 2018.
[10] 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: July 2018.
[11] Bays H. 2013. Sodium Glucose Co-transporter Type 2 (SGLT2) Inhibitors: Targeting the Kidney to Improve Glycemic Control in Diabetes Mellitus. Diabetes Therapy. 4(2): 195–220.
[12] Summary of Product Characteristics. 2018. Invokana 100 mg and 300 mg film-coated tablets. Available at: https://www.medicines.org.uk/emc/medicine/28400. Last Accessed: July 2018.
[13] Stenlof K et al. 2013. Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetes Obes Metab. 15(4):372-82.
[14] Schernthaner G et al. 2013. Canagliflozin Compared With Sitagliptin for Patients With Type 2 Diabetes Who Do Not Have Adequate Glycemic Control With Metformin Plus Sulfonyluea. Diabetes Car. 36(9): 2508-2515.
[15] Lavalle-Gonzalez F J et al. 2013. Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial. Diabetologia. 56(12): 2582–2592.
[16] Cefalu W T et al. 2013. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet. 382 (9896):941-950.
[17] Bode B et al. 2013. Efficacy and safety of canagliflozin treatment in older subjects with type 2 diabetes mellitus: a randomized trial. Hosp Pract. 41(2):72-84.
[18] Neal B et al. 2017.Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. NEJM. 377:644-57.
[19] Diabetes.co.uk. 2018. Type 2 Diabetes. Available at: http://www.diabetes.co.uk/type2-diabetes.html Last Accessed: July 2018.
[20] Diabetes.co.uk. 2018. Diabetes and Obesity. Available at: http://www.diabetes.co.uk/type2-diabetes.html. Last Accessed: July 2018.
