China’s National Medical Products Administration (NMPA) has updated the label for AstraZeneca’s Forxiga (dapagliflozin) to include data from the DECLARE-TIMI 58 phase III trial.
DECLARE-TIMI 58 demonstrated that Forxiga achieved a statistically significant reduction in the composite endpoint of hospitalisation for heart failure (hHF) or cardiovascular (CV) death, versus placebo, in adults with type-2 diabetes (T2D) and established CV disease or multiple CV risk factors. The trial confirmed the well-established safety profile of Forxiga.
There are an estimated 463 million people living with diabetes worldwide, with nearly 120 million in China. Patients with T2D are two to five times more likely to develop chronic heart failure (HF) than those without T2D.
Ruud Dobber, executive vice president, BioPharmaceuticals Business Unit said, “Heart failure is one of the first cardiovascular complications for patients with type-2 diabetes. The DECLARE-TIMI 58 phase III data show that Forxiga reduces the risk of hospitalisation for heart failure and, with this label update, we look forward to bringing this significant benefit to patients in China.”
Forxiga is indicated as a monotherapy and as part of combination therapies to improve glycaemic control in adults with T2D. The NMPA label update, based on the DECLARE-TIMI 58 phase III data, follows the update to the EU marketing authorisation in August 2019 and the approval by the US Food and Drug Administration (US FDA) in October 2019 of an indication for Forxiga (known as Farxiga in the US) to reduce the risk of hHF in adults with T2D and established CV disease or multiple CV risk factors.
In May 2020, Farxiga was approved in the US to reduce the risk of CV death and hHF in adults with HF (NYHA class II-IV) with reduced ejection fraction (HFrEF) with and without T2D, and in October 2020 Forxiga was recommended for approval for HF in the EU by the Committee for Medicinal Products for Human Use. Additionally, the US FDA granted Farxiga Breakthrough Therapy Designation in October 2020 to accelerate the development and regulatory review for patients with chronic kidney disease (CKD), with and without T2D.
Type-2 diabetes is a chronic disease characterised by pathophysiologic defects leading to elevated glucose levels, or hyperglycaemia. Over time, this sustained hyperglycaemia contributes to further progression of the disease. The prevalence of diabetes is projected to reach 578 million people worldwide by 2030, and 700 million by 2045. T2D accounts for approximately 90-95 percent of all cases of diagnosed diabetes.
DECLARE-TIMI 58 is an AstraZeneca-sponsored, phase III, randomised, double-blinded, placebo-controlled, multicentre trial designed to evaluate the effect of Forxiga compared with placebo on CV outcomes in adults with T2D at risk of CV events, including patients with multiple CV risk factors or established CV disease, and also assessed key renal secondary endpoints. The trial included more than 17,000 patients across 882 sites in 33 countries and was independently run in collaboration with academic investigators from the TIMI study group (Boston, US) and the Hadassah Hebrew University Medical Center (Jerusalem, Israel).
Forxiga (dapagliflozin) is a first-in-class, oral, once-daily SGLT2 inhibitor indicated in adults for the treatment of insufficiently controlled T2D as both monotherapy and as part of combination therapy as an adjunct to diet and exercise to improve glycaemic control, with the additional benefits of weight loss and blood-pressure reduction.
Forxiga has been evaluated in patients with CKD in the phase III DAPA-CKD trial, with the full results announced in August 2020 demonstrating that Forxiga met all primary and secondary endpoints, providing overwhelming efficacy. Forxiga is currently being tested for patients with HF in the DELIVER (HF with preserved ejection fraction, HFpEF) and DETERMINE (HFrEF and HFpEF) phase III trials. Forxiga will also be tested in patients without T2D following an acute myocardial infarction (MI) or heart attack in the DAPA-MI trial - a first of its kind, indication-seeking registry-based randomised controlled trial. Forxiga has a robust programme of clinical trials that includes more than 35 completed and ongoing phase IIb/III trials in more than 35,000 patients, as well as more than 2.5 million patient-years’ experience.
AstraZeneca’s Tagrisso (osimertinib) has been approved in China for the adjuvant treatment of patients with early-stage (IB, II and IIIA) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after tumour resection with curative intent, with or without adjuvant chemotherapy as recommended by the patient’s physician. Tagrisso is indicated for EGFRm patients whose tumours have exon 19 deletions or exon 21 (L858R) mutations.
The approval by China’s National Medical Products Administration (NMPA) was based on positive results from the ADAURA phase III trial. In the trial, Tagrisso demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) in the primary analysis population of patients with Stage II and IIIA EGFRm NSCLC. The ADAURA trial also showed a statistically significant and clinically meaningful improvement in DFS in the overall trial population of patients with Stage IB-IIIA disease, a key secondary endpoint.
While up to 30% of all patients with NSCLC may be diagnosed early enough to have surgery with curative intent, recurrence is still common in early-stage disease. Historically, nearly half of patients diagnosed in Stage IB, and over three quarters of patients diagnosed in Stage IIIA, have experienced recurrence within five years. More than a third of the world’s lung cancer patients are in China and among those with NSCLC, approximately 40% have tumours with an EGFR mutation.
Dave Fredrickson, executive vice president, Oncology Business Unit, said, “The expedited approval of Tagrisso in China as part of a curative-intent regimen for early-stage EGFR-mutated lung cancer underscores the high unmet need in this setting and our commitment to improving outcomes in a country with one of the highest rates of EGFR mutations in the world. This approval reinforces the importance of EGFR testing across all stages of lung cancer, prior to treatment decisions, to ensure as many patients as possible can benefit from targeted therapies like Tagrisso and live cancer-free longer.”
In the ADAURA trial, adjuvant treatment with Tagrisso reduced the risk of disease recurrence or death by 83% in patients with stage II and IIIA disease (hazard ratio [HR] 0.17; 99.06% confidence interval [CI] 0.11-0.26; p<0.001) and by 80% in the overall trial population of patients with Stage IB-IIIA disease (HR 0.20; 99.12% CI 0.14-0.30; p<0.001).
Tagrisso is approved to treat early-stage lung cancer in more than a dozen countries, including the US, and additional global regulatory reviews are ongoing. Tagrisso is also approved for the 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC and for the treatment of locally advanced or metastatic EGFR T790M mutation-positive NSCLC in China, and in the US, Japan, the EU and many other countries.
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths. Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC. The majority of NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis. Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.
Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC. These patients are particularly sensitive to treatment with an EGFR-tyrosine kinase inhibitor (TKI) which blocks the cell-signalling pathways that drive the growth of tumour cells.
ADAURA is a randomised, double-blind, global, placebo-controlled phase III trial in the adjuvant treatment of 682 patients with Stage IB, II and IIIA EGFRm NSCLC following complete tumour resection and adjuvant chemotherapy as indicated. Patients were treated with Tagrisso 80mg once-daily oral tablets or placebo for three years or until disease recurrence.
The trial enrolled patients in more than 200 centres across more than 20 countries, including the US, in Europe, South America, Asia and the Middle East. The primary endpoint was DFS in Stage II and IIIA patients and a key secondary endpoint was DFS in Stage IB, II and IIIA patients.
