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Update is based on positive cardiovascular and renal outcomes from CANVAS Programme
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Napp Pharmaceuticals Ltd is Janssen’s partner in diabetes and the exclusive distributor for both Invokana and Vokanamet in the UK
Cambridge, UK: 2nd August 2018. As the exclusive UK distributor of Invokana and Vokanamet, Napp Pharmaceuticals Ltd welcomes the announcement from the Janssen Pharmaceutical Companies of Johnson & Johnson that the Committee for Medicinal Products for Human Use (CHMP), of the European Medicines Agency (EMA), has issued a positive opinion to update the Invokana and Vokanamet labels including changes to the indication statements.
The recommended product information now includes data on the reduction in major adverse cardiovascular events in patients with type 2 diabetes mellitus (T2DM) who had either a history of CV disease or at least two CV risk factors.
Approximately 3.5 million people in the UK are diagnosed with type 2 diabetes.[1] Cardiovascular disease (CVD) is a major cause of death and disability in people with diabetes, accounting for 52% of fatalities in people with T2DM.[2]
“Improvements in glycaemic control, the reduction of cardiovascular morbidity and mortality, as well as improvements in renal outcomes are important in the treatment of type 2 diabetes. As Janssen’s partner of choice in diabetes, we are pleased with the CHMP’s decision to recommend a label update for canagliflozin to include the positive findings from the CANVAS programme. If approved by the European Commission, this will provide a more comprehensive overview of the effects of canagliflozin, and further assist clinicians in making informed treatment decisions that are most appropriate for their patients,” said Paul Schofield, Medical Director, Napp Pharmaceuticals.
The CHMP’s positive opinion will now be reviewed by the European Commission, which has the authority to grant approval of the updated label.
Commenting on the news, Professor Richard Donnelly, Professor in Medicine at The University of Nottingham said, “This change in the licence for canagliflozin will be welcomed by clinicians and GPs. We can now have full confidence to prescribe canagliflozin not only as a glucose-lowering agent, but as a treatment for type 2 diabetes that also confers a substantial reduction in the risk of life-threatening cardiovascular (CV) complications in those high-risk patients who already have established CV disease or multiple CV risk factors.”
The Type II variation application is based on the results of the CANVAS programme, the largest completed CV outcomes trial to date for an SGLT2 inhibitor.[3] The study, which included over 10,000 patients treated since 2009, met its primary endpoint and showed canagliflozin significantly reduced the combined risk of CV death, myocardial infarction and non-fatal stroke, versus placebo in adult patients with T2DM who had either a history of CV disease or at least two CV risk factors.[3]
The current cost to the NHS of direct patient care for people living with type 2 diabetes and its comorbidities is estimated at £8.8 billion annually; and the costs relating to CVD are at £9 billion per year.[4, 5] There is a need for new treatment options that may reduce the burden of potential complications from T2DM to alleviate growing financial pressures on the health service.
Canagliflozin was approved in the European Union by the European Commission in November 2013 and is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus.[6] Approval was based on a comprehensive global Phase III clinical trial programme.
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Notes to editors:
About the CANVAS programme
The CANVAS programme (N=10,142) comprises the two large canagliflozin cardiovascular outcome studies, CANVAS and CANVAS-R, and includes a pre-specified integrated analysis of these two studies to evaluate the potential for CV protection of canagliflozin in patients with T2DM who had either a prior history of CV disease or at least two CV risk factors. The integrated analysis also evaluated the effects of canagliflozin on renal and safety outcomes.[3]
Canagliflozin met the primary outcome by significantly reducing the rates of the composite of major adverse cardiovascular events (MACE) comprised of CV mortality, non-fatal myocardial infarction (MI), or non-fatal stroke (26.9 vs. 31.5/1000 patient-years, hazard ratio (HR) 0.86; 95% confidence interval (CI 0.75-0.97; P<0.001 for noninferiority; P=0.02 for superiority) compared with placebo, respectively. All 3 components of MACE composite (CV death, non-fatal MI, and non-fatal stroke) exhibited point estimates of effect suggesting benefit with canagliflozin.[3]
Adverse events reported in the CANVAS programme were generally consistent with the known safety profile of canagliflozin.[3] However, the study found that, in patients with type 2 diabetes who had established CV disease or at least two risk factors for CV disease, canagliflozin was associated with an approximately 2-fold increased risk of lower limb amputation with the rate of amputation over standard of care being 0.63/100 patient years for canagliflozin versus 0.34/100 patient years for placebo which corresponds to an additional risk of 0.29/100 patient years.[3] The risk of amputations across the class has previously been investigated by the EMA, and this is reflected in a warning in the labelling of all SGLT2 inhibitors.
About Invokana (canagliflozin)
Invokana is a member of a class of drugs known as sodium glucose co-transporter 2 (SGLT2) inhibitors.[7]
SGLT2 inhibitors contribute to controlling blood glucose levels via the kidneys.[8] As glucose is filtered from the blood into the kidneys, it is reabsorbed back into the bloodstream.[8, 9] SGLT2is are an important transport carrier in the kidneys for this reabsorption.[7] 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.[8, 10] This mechanism of action is independent of insulin.[6]
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.[6]
Canagliflozin has been studied as monotherapy and in combination with other type 2 diabetes therapies including insulin.[9] 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).[6] 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.[3] 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, 11, 12] The third study compared canagliflozin to glimepiride (Amaryl®) as dual therapy with metformin which showed a lower risk of hypoglycaemia.10 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.[3, 13, 14]
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.[6]
About Vokanamet (canagliflozin and metformin)
Vokanamet is approved in the European Union to improve glycaemic control of adult patients with type 2 diabetes as an adjunct to diet and exercise and combines two oral glucose-lowering medicinal products with different and complementary mechanisms of action.[15]
About Type 2 Diabetes
Type 2 diabetes is a chronic condition that results in the body being unable to metabolise sugar (glucose). A number of factors can increase the risk of developing type 2 diabetes, including obesity.[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).[17] 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).[18]
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 Diabetes.co.uk. 2018. Diabetes Prevalence. Available at: https://www.diabetes.co.uk/diabetes-prevalence.html. Last Accessed: July 2018.
2 Diabetes UK. 2015. Diabetes: Facts and Stats. https://mrc.ukri.org/documents/pdf/diabetes-uk-facts-and-stats-june-2015/ Last accessed July 2018.
3 Neal B et al. 2017. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. The New England Journal of Medicine. 377(7): 644-57.
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 CVD statistics – BHF UK factsheet. 2018. British Heart Foundation. Available at: https://www.bhf.org.uk/-/media/files/research/heart-statistics/bhf-cvd-statistics—uk-factsheet.pdf?la=en Last Accessed: July 2018.
6 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.
7 Diabetes.co.uk. 2017. Invokana (Canagliflozin). Available at: http://www.diabetes.co.uk/diabetes-medication/invokana-canagliflozin.html. Last Accessed: July 2018.
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: July 2018.
9 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.
10 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.
11 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.
12 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.
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 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.
15 Summary of Product Characteristics. 2018. Vokanamet 50 mg/1000 mg film-coated tablets. Available at: https://www.medicines.org.uk/emc/product/8261/smpc Last accessed July 2018.
16 Diabetes.co.uk. 2018. Type 2 Diabetes. Available at: http://www.diabetes.co.uk/type2-diabetes.html Last Accessed: July 2018.
17 Diabetes.co.uk. 2018. Diabetes and Obesity. Available at: http://www.diabetes.co.uk/type2-diabetes.html. Last Accessed: July 2018.
18 NHS Choices. 2018. Type 2 diabetes. Available at https://www.nhs.uk/conditions/type-2-diabetes/health-problems/. Last Accessed: July 2018.
July 2018 / UK/INV-18153
