Forest Laboratories Announces Positive Phase III Study Results for Nebivolol and Valsartan Combination in Hypertension

Forest Laboratories FRX today announced positive topline results from an 8-week pivotal Phase III clinical trial evaluating the efficacy and safety of investigational fixed dose combination (FDC) of nebivolol and valsartan for the treatment of hypertension. The combination of nebivolol and valsartan demonstrated statistically significant reductions in diastolic blood pressure (DBP) vs. both nebivolol alone and valsartan alone at 8 weeks, which was the primary endpoint. The FDC also met the key secondary endpoint of change from baseline in systolic blood pressure (SBP) at 8 weeks. The single pivotal nebivolol/valsartan FDC trial was designed to meet the required regulatory “Combination Rule,” comparing a FDC against the highest approved dose of each component drug. “These Phase III results in patients with Stage 1 or Stage 2 hypertension are exciting and demonstrate the potential benefits of this novel FDC -- a first-in-class beta blocker/ARB combination,” said Marco Taglietti, MD, Senior Vice President of Research and Development and President, Forest Research Institute. “We are very pleased with these results which demonstrate the efficacy and safety profile of this combination and support the potential use of the nebivolol/valsartan FDC as a new treatment option for patients with hypertension who need dual therapy to reach their blood pressure goals.” Based on these positive results, Forest plans to submit a regulatory filing with the Food and Drug Administration (FDA) in the first quarter of calendar year 2014. About the Phase III Study This pivotal 8-week randomized, double-blind, placebo-controlled clinical trial in 4,161 hypertension patients studied nebivolol 5, 10, 20, and 40mg and valsartan 80, 160, and 320mg alone and in fixed dose combinations. The study consisted of a 1-week screening period, followed by 6 weeks of placebo wash-out, an 8-week double-blind treatment period, and a 1-week down-titration period. During the double-blind treatment period, patients were initially randomized to one of eight treatment groups: FDC nebivolol/valsartan 5/80, 5/160, or 10/160mg; nebivolol 5 or 20mg; valsartan 80 or 160mg or placebo. After four weeks, all dosages were doubled. The primary endpoint was change from baseline in mean sitting trough DBP at 8 weeks for FDC dose 20/320mg versus nebivolol 40mg (the highest approved nebivolol dose) and versus valsartan 320mg (the highest approved valsartan dose), and FDC doses 10/320mg and 10/160mg versus corresponding monotherapies. Across these doses, the incremental reduction in DBP for the combination vs. nebivolol was -1.2 to -2.4 mm Hg; (p value 0.03 to <0.0001) and versus valsartan was -3.7 to -4.4 mm Hg (p value <0.0001). The key secondary endpoint was change from baseline in sitting trough SBP at 8 weeks for the FDC doses 20/320mg, 10/320mg and 10/160mg vs. the same monotherapy components evaluated for DBP. Across these doses, the incremental reduction in SBP for the combination vs. nebivolol was -2.9 to -3.6 mm Hg; (p value 0.0013 to <0.0001) and versus valsartan was -3.0 to -3.9 mm Hg (p value 0.0011 to <0.0001). Treatment with nebivolol/valsartan FDC was well-tolerated in the study. Across all FDC doses the most common adverse events (incidence ≥ 2% and greater than placebo) were fatigue (0.9% to 2.3% vs. 1.1% in placebo) and dizziness (1.6% to 2.3% vs. 0.4% in placebo).