Actavis,  a global, integrated specialty pharmaceutical company,  confirmed that the company has received a complete response letter from the US Food and Drug Administration (FDA) for its New Drug Application (NDA) for the fixed-dose combination (FDC) of nebivolol and valsartan for the treatment of hypertension.  

"Although we are disappointed in the receipt of a complete response letter, Actavis remains committed to bringing treatments to market that address the significant public health issue of cardiovascular disease," said David Nicholson, senior vice president, Actavis Global Brands R&D. "Bystolic is a safe and effective option that is commonly used in combination with other antihypertensive medications to help patients reach blood pressure treatment goals. We will review the complete response and determine the appropriate next steps."

Data submitted to the FDA in support of approval of this NDA included a single phase III randomized, controlled trial of approximately 4,100 patients. In this pivotal efficacy study, the FDC of nebivolol and valsartan met its primary and key secondary endpoints, demonstrating statistically significant reductions from baseline in diastolic and systolic blood pressure at eight weeks in patients with hypertension, versus both nebivolol alone and valsartan alone, including either monotherapy agent at its highest doses. The rate of patients experiencing at least one treatment-emergent adverse event was similar across treatment groups and placebo. In addition, a 52-week open-label safety study was conducted to describe the long-term safety profile of the nebivolol/valsartan combination. As of 2014 data, the worldwide exposure of each component drug has been 40 million patient-years for nebivolol and 180 million patient-years for valsartan.

According to the CDC, hypertension has been called the "silent killer" because it often has no warning signs or symptoms and has been associated with serious cardiovascular (CV) risks, such as stroke and myocardial infarction. Hypertension represents a significant public health issue with high prevalence in the United States. According to the National Institute for Health Statistics, approximately 30 per cent of adults in the United States have hypertension. Inadequate control of hypertension is a significant public health problem, with approximately half of all patients still not achieving target goals. Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce CV morbidity and mortality, and it can be concluded that blood pressure reduction is largely responsible for those benefits. In addition, approximately two-thirds of hypertensive patients will require more than one drug to achieve blood pressure goals, further emphasising the importance of antihypertensive drug combinations and of studies of safety and efficacy such as this programme's.