Green light for new two-drug therapy from AstraZeneca
AstraZeneca’s two-drug therapy Qtern (saxagliptin and dapagliflozin fixed-dose combination) is now available in the UK for adults with type 2 diabetes.
Saxagliptin and dapagliflozin fixed-dose combination (saxa/dapa FDC) is a once-daily tablet that combines saxagliptin 5mg, a dipeptidyl peptidase-4 (DPP-4) inhibitor, with dapagliflozin 10mg, a sodium-glucose co-transporter 2 (SGLT2) inhibitor. This is the first launch of saxa/dapa FDC globally.
Saxa/dapa FDC received arketing authorisation from the European Commission in July 2016 and is indicated in adults aged 18 years and older with type 2 diabetes, to improve glycaemic control when metformin and/or sulphonylurea (SU) and one of the mono-components of saxa/dapa FDC do not provide adequate control, or when a patient is already being treated with the free combination of saxagliptin and dapagliflozin.
Professor Luigi Gnudi – professor of diabetes and metabolic medicine, honorary consultant in diabetes and endocrinology, head of the unit for metabolic medicine, cardiovascular division, King’s College London, Guy’s and St Thomas NHS Foundation Trust – said: “DPP-4 inhibitors and SGLT2 inhibitors are commonly prescribed together as they have complementary mechanisms of action to help improve glycaemic control in people with type 2 diabetes. Being available together in a single tablet provides another treatment option that can help to improve glycaemic control while reducing the pill burden. As a complex, progressive disease with many comorbidities, this is a welcome development for patients.”
The European approval was based on data from three Phase III randomised, double-blind, active/placebo-control, parallel group, multi-centre clinical trials in 1,169 adults with type 2 diabetes.
In one study where saxagliptin 5mg or placebo was added to patients treated with dapagliflozin 10mg and metformin, mean changes from baseline HbA1c were -0.51 per cent (95 per cent CI -0.63 to -0.39) and -0.16 per cent (95 per cent CI -0.28 to -0.04) respectively at 24 weeks. The proportion of patients achieving a HbA1c of less than seven per cent at week 24 was higher in the saxagliptin plus dapagliflozin plus metformin group 35.3 per cent (95 per cent CI [28.2, 42.2]) compared to the placebo plus dapagliflozin plus metformin group 23.1 per cent (95 per cent CI [16.9, 29.3]). The effect in HbA1c observed at week 24 was sustained at week 52.
The safety profile of saxa/dapa FDC was comparable to the known safety profiles of saxagliptin and dapagliflozin. The most frequently reported adverse reactions were hypoglycaemia (when used with a SU) and upper respiratory tract infection. Common adverse reactions are genital and urinary tract infections, gastroenteritis, dyslipidaemia, headache, dizziness, abdominal pain, diarrhoea, dyspepsia, gastritis, nausea, vomiting, dysuria, polyuria, rash, arthralgia, back pain, myalgia, fatigue and oedema, creatinine clearance decreased, haematocrit decreased. One uncommon and one rare adverse reaction were reported; pancreatitis and diabetic ketoacidosis, respectively.
Lisa Anson, country president, AstraZeneca UK, said: “Almost three-quarters (74 per cent) of people with type 2 diabetes in the UK are not reaching the recommended HbA1ctarget of 6.5 per cent, which means they are at increased risk of the complications associated with the condition. AstraZeneca is pleased to offer another treatment option in the diabetes portfolio to help patients reach their targets, enabling clinicians to continue oral therapy with a once-daily tablet.”
NICE will not appraise saxa/dapa FDC and hence decisions on its use in NHS England will be taken at a local level. The Scottish Medicines Consortium (SMC) and All Wales Medicines Strategy Group (AWMSG) will appraise saxa/dapa FDC in 2017 in line with their standard processes.