MUNDIPHARMA

As the European distributor of Invokana^® (canagliflozin) and Vokanamet^® (canagliflozin and metformin), Mundipharma welcomes the publication of the first KDIGO (Kidney Disease: Improving Global Outcomes) 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (CKD). The new guideline recommends the use of sodium-glucose co-transporter-2 inhibitor (SGLT2i) class, which includes canagliflozin, as a first-line treatment option alongside metformin for the management of hyperglycaemia in patients with type 2 diabetes mellitus (T2DM), CKD and eGFR ≥30 ml/min/1.73 m² .¹

This new guideline includes data from CV outcomes trials (CVOTs) for SGLT2is which give evidence of significant cardioprotective and possible kidney-protective effects across the class. This includes the positive CV outcomes data for canagliflozin,² empagliflozin and dapagliflozin, and CKD outcomes from the canagliflozin CREDENCE clinical trial.³ The guideline also highlights that whilst kidney events were secondary outcomes in most of the CVOTs, CREDENCE was the first randomised controlled trial specifically powered for primary renal outcomes among patients exclusively with albuminuric CKD.³

The CREDENCE trial is the first dedicated renal outcomes study in patients with DKD and T2DM. The study enrolled 4401 subjects with an eGFR of 30 to <90ml/min/1.73m² and albuminuria (urinary albumin: creatinine ratio >300 to 5000 mg/g). Importantly, all patients were treated on a background of standard of care for DKD, including a maximum tolerated dose of an ACE inhibitor or ARB. The results showed that canagliflozin demonstrated a 30% reduction, compared to placebo, in the risk of the primary composite endpoint, comprising end-stage renal disease (ESRD), doubling of serum creatinine and renal or cardiovascular (CV) death, with event rates of 43.2 vs 61.2 per 1000 patient years, respectively (Hazard Ratio [HR]: 0.70; 95% Confidence Interval [CI]: 0.57 to 0.84; p<0.0001).⁵

Canagliflozin received approval from the European Commission (EC) in July this year, to extend its treatment of T2DM indication in Europe to treat diabetic kidney disease (DKD) in T2DM patients.⁶ It is currently the only SGLT2i labelled to treat DKD in TD2M patients.

“The KDIGO recommendations are based on evidence from recent clinical trials. These trials include CREDENCE, which demonstrated that canaglifozin reduced the risk of deteriorating kidney function and associated cardiovascular complications in patients with both type 2 diabetes and chronic kidney disease. CREDENCE is one reason why SGLT2 inhibitors have been given a prime position in diabetes management in the guideline,” said Professor David Wheeler, Professor of Kidney Medicine at University College London and Honorary Consultant Nephrologist at the Royal Free NHS Foundation Trust, London, UK.

An estimated 59 million adults in Europe currently live with diabetes and around 90% of these have T2DM. This figure is set to rise to 68 million by 2045.⁷ If left untreated, people with T2DM are at greater risk of developing serious health complications, such as CKD, heart failure (HF), and CV disease, which is the most common cause of death amongst them.⁸ It is estimated that approximately 40% of people with T2DM will go on to develop CKD,⁴ so effective therapies need to be sought rapidly to halt the progression of the disease.¹

“People with type 2 diabetes and chronic kidney disease are at greater risk of cardiovascular disease and progression to end-stage kidney disease, so it is of paramount importance that physicians have clear guidelines which recommend appropriate therapies to help prevent these risks,” said Dr Vinicius Gomes de Lima, European Medical Affairs Lead, Mundipharma.

The KDIGO guideline can be viewed at: https://kdigo.org/wp-content/uploads/2018/03/KDIGO-Diabetes-in-CKD-GL.pdf .

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Notes to the editors:

About the KDIGO Guideline¹
The first KDIGO (Kidney Disease: Improving Global Outcomes) Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease was published in https://kdigo.org/wp-content/uploads/2018/03/KDIGO-Diabetes-in-CKD-GL.pdf .

About Invokana^® (canagliflozin)
Canagliflozin is an oral, once-daily medication that belongs to a class of medications called sodium glucose co-transporter 2 (SGLT2) inhibitors. SGLT2 inhibitors work by inhibiting SGLT2 co-transporter, which promotes the excretion of glucose via the urine, and thus helps lowering blood glucose levels in adults with T2DM.⁵

Canagliflozin was approved in the European Union by the European Commission in November 2013. It is indicated for the treatment of adults with insufficiently controlled T2DM as an adjunct to diet and exercise, as monotherapy when metformin is considered inappropriate due to intolerance or contra-indications and in addition to other medicinal products for the treatment of diabetes.⁵

The recommended initiation dose of canagliflozin is 100 mg once daily in adults with an eGFR of ≥ 60 mL/min/1.73 m² and can be increased to 300 mg once daily if tighter glycaemic control is needed. For patients with an eGFR of 45 to <60 mL/min/1.73 m² the initiation dose is limited to 100mg once daily, if further glycaemic control is needed the addition of other anti-hyperglycaemic agents should be considered. In patients with an eGFR of 30 to < 45 mL/min/1.73 m² with a urinary albumin/creatinine ratio ˃ 300 mg/g, the initiation dose is limited to 100 mg once daily, if further glycaemic control is needed the addition of other anti-hyperglycaemic agents should be considered. Canagliflozin should not be initiated if eGFR is below 30 mL/min/1.73 m² , but for patients already taking canagliflozin it should be continued at 100 mg until dialysis or renal transplantation is required.⁵

Approval was based on a comprehensive global Phase III clinical trial programme.

About the CANVAS Programme²
The CANVAS Programme (N=10,142) comprised the two large canagliflozin cardiovascular outcome trials, CANVAS and CANVAS-R, and included 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.

Canagliflozin met the primary outcome by significantly reducing the rates of the composite of major adverse CV 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<0.0001 for non-inferiority; P=0.0158 for superiority) compared with placebo plus standard of care, 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.

Adverse events reported in the CANVAS Programme were generally consistent with the known safety profile of canagliflozin. Whilst an increase in lower limb amputation and bone fractures were observed in the CANVAS Programme, this signal was not observed in further long term clinical trial data involving high risk patients.³

About the CREDENCE Clinical Trial³
The CREDENCE (C anagliflozin and R enal E vents in D iabetes with E stablished N ephropathy C linical E valuation) study was the first dedicated and fully recruited renal outcome trial evaluating renal and cardiovascular outcomes in people with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) with a sodium glucose co-transporter 2 (SGLT2) inhibitor. It was a phase III randomised, double-blind, event-driven, placebo-controlled, parallel-group, two-arm multicentre study of the effects of canagliflozin on renal and cardiovascular outcomes in subjects with T2DM and CKD. In particular, it compared the efficacy and safety of canagliflozin versus placebo in preventing clinically important kidney and cardiovascular outcomes in patients with T2DM and CKD 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).

About the Mundipharma network
Mundipharma is a global (ex-US) network of privately-owned independent associated companies with a presence across Africa, Asia Pacific, Europe, Canada, Latin America and the Middle East.

We are dedicated to bringing to patients with severe and debilitating diseases the benefit of novel treatment options in fields such as Anti-Infectives, Biosimilars, CNS, Diabetes, Oncology & supportive care, Ophthalmology, Pain Management, Respiratory and Consumer Healthcare.

For further information by geographic region please go to www.mundipharma.com (Europe); www.purdue.ca (Canada) and www.mundipharma.com.sg (other ex-US markets).

Invokana^® is a registered trademark of Johnson & Johnson. The Marketing Authorisation Holder is Janssen-Cilag International NV.

References:

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¹ KDIGO 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney International . Oct 2020; 98(4S): S1–S115. Available at https://kdigo.org/wp-content/uploads/2018/03/KDIGO-Diabetes-in-CKD-GL.pdf . Last accessed September 2020.

² Neal B et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. The New England Journal of Medicine (2017);377:644-657.

³ Perkovic, V. et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephrology. The New England Journal of Medicine. 2019; 380(24): 2295-2306.

⁴ Alicic R, Rooney M, Tuttle K. Diabetic Kidney Disease: Challenges, Progress, and Possibilities. Clin J Am Soc Nephrol. 2017; 12(12):2032-45.

⁵ Invokana SMPC. Updated July 2020 https://www.medicines.org.uk/emc/product/8855 Last accessed July 2020

⁶ European Commission. 26th June 2020 Decision C(2013)8171(final) for Invokana – canagliflozin. Available at https://ec.europa.eu/health/documents/community-register/html/h884.htm . Last accessed July 2020.

⁷ IDF Diabetes Atlas Ninth Edition 2019. Available at: https://www.diabetesatlas.org/en/resources/ Last accessed July 2020

⁸ Einarson T, Acs A, Ludwig C. et al. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007-2017. Cardiovasc Diabetol. 2018 Jun 8;17(1):83.

Job code: MINT/MINVK-20034
Date of preparation: October 2020

View source version on businesswire.com: https://www.businesswire.com/news/home/20201001006167/en/