Doubts dog new anticoagulant uptake
This article was originally published in Scrip
Experts are struggling to predict what the pattern of uptake will be of the new oral anticoagulants for the stroke prevention in atrial fibrillation (SPAF) market. While nobody can dispute the need for alternatives to warfarin, there are concerns over the lack of antidotes to reverse bleeding, and ambiguity over the appropriate patient populations to be treated with the latest products.
"Key opinion leaders and physicians are split over the likely impact of bleeding reversal concerns on uptake in a market undergoing a paradigm shift in treatment practices," Datamonitor Healthcare analyst Victoria Hudson told Scrip.
As a result, Datamonitor has taken the unusual step of publishing a two-scenario forecast to reflect the sales potential of the new products.
The new anticoagulants are: the direct thrombin inhibitor dabigatran (Pradaxa, Boehringer Ingelheim; the first to be approved, in October 2010), and the factor Xa inhibitors rivaroxaban (Xarelto, Bayer/Johnson & Johnson), apixaban (Eliquis, Bristol-Myers Squibb/Pfizer).
According to the new analysis published by Datamonitor, Forecast: Stroke Prevention in Atrial Fibrillation, the novel oral anticoagulants are expected to show a combined annual growth rate of 1.3% in the first scenario versus -3.18% in the second over the 2017–2021 period.
"The uncertainties mainly relate to a lack of standard procedures to treat patients undergoing a serious bleeding event. Through the use of two scenarios, worst- and best-case scenarios can be examined in the forecast," explained Ms Hudson.
In scenario one, uptake of the novel oral anticoagulants is expected to be limited by bleeding reversal concerns until the launch of the antidotes in 2017 and 2019. Physicians are expected to be reluctant to switch their patients from standard therapy warfarin or aspirin or prescribe the new products to treatment-naïve patients. The SPAF market is expected to show a compound annual growth rate CAGR of 9% over 2012–21 in scenario one.
In scenario two, the benefits of the new therapies versus warfarin will drive faster uptake, with bleeding reversal concerns being addressed prior to the launch of the antidotes in 2017 and 2019.
Sales of the novel oral anticoagulants are expected to demonstrate a compound annual growth rate (CAGR) of 14% in scenario one over 2012–2017, compared to 24% in scenario two over the same time period.
Of the three newer products, Eliquis – with its strong Phase III safety data versus either warfarin or aspirin (ARISTOTLE and AVERREOES – is expected to become the market leader. However, concerns over bleeding reversal are expected to delay its march to the top in scenario one versus scenario two. Eliquis is not expected to overtake Pradaxa and Xarelto as the leading brand until the launch of the universal Factor Xa inhibitor in 2017, with peak sales only reaching $1.95bn in 2021.
However, in scenario two, the market is forecast a CAGR of 12% over 2012–2021. Eliquis is expected to become the market leader as early as 2014, with peak sales of $2.79bn in 2021.
concerns
The nature of anticoagulation prophylaxis places predominately frail and elderly patients at great risk in the event of a major bleed. The current anticoagulants such as warfarin have standardized procedures and antidotes to treat patients undergoing a serious bleeding event but, as the novel oral anticoagulants are still relatively new to clinical practice, these procedures and antidotes are still in development.
The first antidote for the novel oral anticoagulants is not expected to be available until 2017. However, once launched they are expected to relieve concerns over bleeding reversal and lead to an increase in the uptake of the novel oral anticoagulants.
A universal Factor Xa inhibitor antidote (PRT-4445; Portola Pharmaceuticals) is currently undergoing Phase II trials. The antidote is being tested on patients receiving the SPAF therapies Eliquis and Xarelto (scripintelligence.com, 6 February 2013). Boehringer Ingelheim is developing an antidote to Pradaxa, which is currently in Phase I trials.