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CHMP Adopts Positive Opinion for Rivaroxaban in Combination with Aspirin for CAD and PAD Patients

Jul 30, 2018 18:52 CST Updated 18:52
Bayer

Pharmaceutical Product R&D Developer

Committee for Medicinal Products for Human Use

Committee for Medicinal Products for Human Use (CHMP)The Committee for Medicinal Products for Human Use (CHMP) is the committee within the European Medicines Agency (EMA) responsible for human medicines. The CHMP replaced the former Committee for Proprietary Medicinal Products (CPMP) in May 2004.The CHMP plays a vital role in the authorization of medicines in the European Union (EU). In the centralized procedure, the CHMP is responsible for: 1) conducting initial assessments of marketing authorization applications across the EU; assessing modifications or extensions to existing marketing authorizations (“variations”); considering recommendations from the Agency’s Pharmacovigilance Risk Assessment Committee regarding the safety of medicines on the market, and, where necessary, advising the European Commission to amend the marketing authorization of a medicinal product, or to suspend or withdraw it from the market.The CHMP also evaluates medicines authorized at the national level that are referred to the EMA, with the aim of maintaining a harmonized position throughout the EU.Furthermore, the CHMP and its working groups promote the development of medicines and pharmaceutical regulation by: providing scientific advice to companies researching and developing new medicines; developing scientific and regulatory guidelines to assist pharmaceutical companies in preparing marketing authorization applications for human medicines; and collaborating with international partners to harmonize regulatory requirements.

July 27, 2018: The Committee for Medicinal Products for Human Use of the European Medicines Agency adopted [an opinion/recommendation] regarding Bayer’s oral Factor Xa inhibitor, Xarelto®(Positive opinion on the new indication for rivaroxaban.) Xarelto (2.5 mg twice daily) in combination with aspirin (75–100 mg once daily) will be indicated for adult patients with coronary artery disease or symptomatic peripheral artery disease at high ischemic risk, to prevent atherothrombotic events.

The positive opinion is based on data from the COMPASS clinical trial, the largest Phase III study of rivaroxaban, which enrolled 27,395 patients. The results demonstrated that, compared with aspirin 100 mg once daily alone, rivaroxaban at an arterial dose of 2.5 mg twice daily plus aspirin 100 mg once daily significantly reduced the composite risk of stroke, cardiovascular death, and myocardial infarction by 24% (relative risk reduction) in patients with coronary artery disease or peripheral artery disease.

“Despite guideline-recommended treatment, patients with coronary artery disease (CAD) and peripheral artery disease (PAD) still experience high rates of events (myocardial infarction, stroke, and even death),” said Dr. Joerg Moeller, Member of the Executive Committee of Bayer’s Pharmaceuticals Division and Head of Research and Development. “Today’s positive opinion from the Committee for Medicinal Products for Human Use brings us one step closer to providing an important new treatment option for these patients.” Once approved, rivaroxaban will be the only non-vitamin K antagonist oral anticoagulant (NOAC) indicated in combination with aspirin for adult patients with CAD or symptomatic PAD at high ischemic risk, to prevent atherothrombotic events.

Cardiovascular diseases (including coronary artery disease and peripheral artery disease) cause 17.7 million deaths annually, accounting for 31% of all global deaths.[i]. Additionally, patients with cardiovascular disease have a reduced life expectancy of more than 7 years[ii]Coronary artery disease and peripheral artery disease are chronic, progressive conditions caused by atherosclerosis, characterized by the formation and rupture of atherosclerotic plaques on arterial walls.[iii],[iv]. Patients with this disease are at risk of thrombotic events, which may lead to disability, amputation, and death.

Although current treatment guidelines recommend antiplatelet therapy (e.g., aspirin), its efficacy is suboptimal.[v],[vi]. Further improvement in antithrombotic therapy requires the exploration of novel approaches, such as dual-pathway thrombosis inhibition, to enhance vascular protection and reduce the burden of cardiovascular events.

In addition to significantly reducing the composite efficacy endpoint of major adverse cardiovascular events (MACE), data from the COMPASS study also demonstrated that rivaroxaban at an arterial dose of 2.5 mg twice daily plus aspirin 100 mg once daily significantly reduced the risk of stroke by 42% (relative risk reduction) and the risk of cardiovascular death by 22%, compared with aspirin 100 mg once daily alone. Furthermore, the combination therapy improved clinical net benefit by 20%, a conclusion reached after balancing its efficacy in reducing stroke, cardiovascular death, and myocardial infarction against the risk of the most severe bleeding events.

The incidence of bleeding was low; although major bleeding increased, there was no significant increase in intracranial or fatal bleeding. More importantly, among patients with peripheral artery disease, the composite risk of major adverse limb events and major amputations due to vascular causes was significantly reduced. Therefore, this novel therapy offers significant advantages in the management of patients with peripheral artery disease who are already receiving antiplatelet therapy but remain at high risk for atherothrombotic events.

Additionally, the results of the COMPASS study are under review by the U.S. Food and Drug Administration as part of the supplemental New Drug Application for two new indications of rivaroxaban. The two new indications are: reducing the risk of major adverse events, including cardiovascular death, myocardial infarction, or stroke, in patients with stable coronary artery disease and/or peripheral artery disease; and reducing the risk of acute limb ischemia in patients with peripheral artery disease.

References:

[i] World Health Organization. Cardiovascular Diseases Factsheet http://www.who.int/gho/publications/world_health_statistics/en/. Accessed April 2018.
[ii] Crimmins E, Hayward M, Hiroshi U, et al. Life with and without heart disease among women and men over 50. J Women Aging 2008; 20(1-2): 5–19.
[iii] NHS Choices. Coronary heart disease. https://www.nhs.uk/conditions/coronary-heart-disease/. Accessed April 2018.
[iv] NHS Choices. Peripheral arterial disease. https://www.nhs.uk/conditions/peripheral-arterial-disease-pad/. Accessed April 2018.
[v] Montalescot G, Sechtem U, Achenbach S, et al. Eur Heart J 2013;34 :2949–3003.
[vi] Aboyans V, Ricco JB, Bartelink ML, et al. Eur Heart J 2017;39(9):763-816.

Editor:Li Baowei