LCZ696’s (near) future looks even brighter with an additional FDA incentive.
The US Food and Drug Administration (FDA) has granted priority review to the chronic heart failure drug LCZ696 (valsartan/sacubitril; Novartis), shortening its appraisal time by four months.
By Inês Guerra, Analyst
19 February 2015
I joined Datamonitor Healthcare as an analyst in early 2015, having completed a Master’s degree in Pharmaceutical Scie...
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On 13 February 2015, Novartis announced that the FDA had granted its much anticipated drug LCZ696 a priority review. With the designation leading to a shorter review time, the FDA is expected to make a decision on the drug’s approval as early as August 2015 (Novartis, 2015). Promisingly for Novartis, this is one of a number of encouraging nods for LCZ696 from regulators. In 2014, the FDA granted the drug fast track designation, and agreed to a rolling submission. Similarly, in November 2014, the European Medicines Agency (EMA) accepted Novartis’s request for an accelerated assessment (Novartis, 2014a).
LCZ696 is a first-in-class angiotensin receptor-neprilysin inhibitor consisting of valsartan and sacubitril. Valsartan is an angiotensin receptor blocker that competes with angiotensin II for binding to the AT1 receptor. Sacubitril is a prodrug that inhibits neprilysin, an enzyme responsible for the breakdown of several vasoactive peptides. Their combined action reduces vasoconstriction and sodium retention, helping improve some of the underlying causes of chronic heart failure (CHF) (Athyros et al., 2014; Packer et al., 2015).
The number of tools that the FDA and EMA are using to grant LCZ696 market authorization only serves to highlight the drug’s potential as a game-changing therapy within CHF. The priority review, the fast track designation, and the accelerated assessment are some of the initiatives developed by the FDA and EMA to speed up patients’ access to medicines. While they are in fact distinct approaches, all of them are directed at treatments considered to be of added value. This includes drugs that would target an unmet medical need, and that appear to have improved safety or efficacy over the available alternatives.
LCZ696 demonstrated improved efficacy over the gold-standard enalapril in the widely anticipated PARADIGM-HF pivotal study, justifying the priority review. When compared to enalapril, LCZ696 led to a 20% reduction in the risk of cardiovascular death (p<0.001), a 16% decrease in the risk of all-cause death (p<0.001), and 21% fewer heart failure (HF) hospitalizations (p<0.001). PARADIGM-HF was a randomized, double-blind, Phase III study that compared the efficacy and safety of LCZ696 versus enalapril. It was the largest heart failure study ever undertaken, including 8,442 HF patients with reduced ejection fraction. The trial results were presented at the 2014 European Society of Cardiology Congress in Barcelona, following the trial’s early termination due to the drug’s overwhelming benefit (Novartis, 2014b).
Not only is LCZ696 an attractive proposition for regulators and physicians, but also for payers. The drug addresses a major factor in CHF economic burden by demonstrating a reduction in hospitalization rates. In decreasing these rates relative to the current standard of care, payers should look more favorably on a therapy that is expected to compete with the widely genericized angiotensin-converting enzyme inhibitors. With the prevalence of CHF forecast to increase, the disease’s economic burden is also expected to place further pressure on payers (Novartis, 2015). A green light from the health technology assessment bodies should contribute to greater physician uptake and good market penetration.
Considering the FDA’s increasingly higher regulatory and safety requirements, the additional priority review designation only solidifies LCZ696’s reputation as a potential blockbuster. By granting a priority review, the FDA recognizes the drug’s significance in the treatment of a disease with a growing prevalence and poor prognosis. LCZ696 has the potential to change the CHF treatment paradigm while significantly boosting Novartis’s revenue, with Datamonitor Healthcare forecasting annual sales to reach $6bn in 2023. Moreover, LCZ696 will also aid the company’s cardiovascular portfolio, which is currently struggling following Diovan’s (valsartan) patent expiry in the EU, US, and Japan, as well as the launch of generic competition (Novartis, 2014c).
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Posted in Cardiovascular.