AstraZeneca’s Brilinta (ticagrelor) met its primary endpoint in the Phase III THALES trial, boosting the blockbuster drug’s prospects in prevention of acute ischemic stroke (AIS) and transient ischemic attack (TIA).
GlobalData believes that Brilinta’s use in these patients will significantly increase even before the approval in these indications, as the drug is currently used off-label in AIS and TIA patients, albeit very rarely. Nevertheless, the drug will face fierce competition with much cheaper clopidogrel (Plavix generics) and therefore AstraZeneca may focus on a very specific patient population (carriers of the CYP2C19 loss-of-function allele) to effectively capture a portion of the stroke market and significantly boost drug sales.
In combination with aspirin, Brilinta significantly decreased the risk of stroke or death over aspirin alone in patients who had suffered AIS or TIA and began treatment within 24 hours for 30 days. Provided the approval is obtained for the use of aspirin / Brilinta dual antiplatelet therapy (DAPT) in AIS and TIA, physicians would use the twice-daily Brilinta as a short-term 30-day treatment, as tested in the THALES trial. Previously, GlobalData’s primary research showed a very low level of off-label use of Brilinta globally, while in some countries, like the UK and Japan, no off-label use of this drug was detected.
Combining antiplatelet drugs to maximise efficacy is a common strategy in stroke prevention and the combination of aspirin and clopidogrel is the most commonly prescribed DAPT. Clinical trials have been investigating antiplatelet combinations that could be superior to aspirin monotherapy. In the POINT trial, clopidogrel combined with aspirin demonstrated reduced risk of major ischemic events occurring in patients with minor AIS or high-risk TIA. However, the trial also reported a higher risk of haemorrhage at 90 days in patients receiving the combination.
Some studies have shown that patients with minor AIS or TIA who are treated with Brilinta plus aspirin have a lower proportion of high platelet reactivity than those who are treated with clopidogrel plus aspirin, particularly for those who are carriers of the CYP2C19 loss-of-function allele.
GlobalData believes that Brilinta will likely be used as an add-on to aspirin in AIS and TIA patients carrying the CYP2C19 loss-of-function gene, as clopidogrel has decreased antiplatelet efficacy in patients who are poor metabolisers of CYP2C19. By targeting a niche population with specific unmet needs, the drug could steal some patient share from the much cheaper clopidogrel generics.
Brilinta is approved in all major markets for the treatment of acute coronary syndrome and for the secondary prevention of cardiovascular events among high-risk patients who have experienced a heart attack. Penetrating even a small portion of the stroke market would significantly boost the drug’s sales, as clopidogrel sales in 2019 (Plavix and clopidogrel generics), for stroke patients alone, were estimated to be close to $1bn, according to a GlobalData report.