U.S. FDA Approves Expanded Indication for Xarelto™ Plus Aspirin in Patients with Symptomatic PAD Following Lower Extremity Revascularization

Janssen Pharmaceuticals, a Johnson & Johnson (JNJ) company, recently announced that the U.S. Food and Drug Administration (FDA) has approved an expanded peripheral artery disease (PAD) indication for Xarelto (rivaroxaban): Xarelto (vascular dose, 2.5 mg twice daily) in combination with aspirin (100 mg once daily) is indicated to reduce the risk of major thrombotic vascular events (such as heart attack and amputation) in patients with symptomatic PAD who have recently undergone lower extremity revascularization (LER).

Previously, Xarelto was approved for use in combination with aspirin to reduce the risk of major cardiovascular (CV) events (CV death, myocardial infarction, and stroke) in patients with chronic coronary artery disease (CAD) or peripheral artery disease (PAD). Xarelto is the first and only medication indicated for both CAD and PAD, and will now also include PAD patients following lower extremity revascularization (LER). Xarelto is the first anticoagulant in 20 years to demonstrate significant efficacy in PAD patients who remain at high risk for major thrombotic events, including acute limb ischemia and amputation. PAD affects 20 million people in the United States, is the leading cause of amputation, and amputation rates have continued to rise in recent years.

Xarelto is an oral Factor Xa inhibitor. It is the most widely prescribed non-vitamin K antagonist oral anticoagulant (NOAC) globally. The drug is currently approved for multiple therapeutic indications, which vary by country, and has been approved for 9 indications in the United States. Compared with other NOACs, Xarelto benefits a broad patient population by preventing various venous thromboembolism (VTE) and arterial thromboembolism (ATE) conditions.

Xarelto was co-developed by Bayer and Johnson & Johnson, and has received regulatory approval in over 100 countries worldwide. Johnson & Johnson is responsible for sales in the U.S. market, while Bayer handles markets outside the U.S. According to financial reports from both companies, Xarelto's global sales reached $7.5 billion in 2020.

VOYAGER PAD Study Results (Image source: NEJM, PMID: 32222135)

Peripheral artery disease (PAD) is a chronic circulatory disease that causes narrowing of the blood vessels, thereby reducing blood flow to the limbs (most commonly the legs). An estimated 20 million people in the United States alone have PAD, yet only 8.5 million are currently diagnosed with the condition. Although typically asymptomatic at onset, PAD can progress to severe symptoms requiring revascularization to prevent amputation. PAD is the leading cause of amputation in the United States and is associated with a high incidence of fatal and nonfatal cardiovascular events. Amputation is a devastating complication of PAD that, although largely preventable, is associated with high mortality rates.

This approval is based on data from the Phase 3 VOYAGER PAD study. The study demonstrated that, compared with aspirin (100 mg once daily), the combination of Xarelto (2.5 mg twice daily) and aspirin (100 mg once daily) reduced the risk of major adverse limb and cardiovascular events by 15% in patients with peripheral artery disease (PAD) following lower extremity revascularization (LER). The trial also found no significant difference in TIMI major bleeding between the Xarelto plus aspirin combination regimen and aspirin alone.

Results from the VOYAGER PAD trial complement those of the landmark Phase 3 COMPASS trial, which also evaluated dual pathway inhibition with Xarelto plus aspirin in patients with CAD and/or PAD, and further support this FDA label expansion for patients with PAD. Based on data from the COMPASS trial, the FDA approved the Xarelto plus aspirin regimen in 2018 to reduce the risk of major cardiovascular events, such as heart attack, stroke, and cardiovascular death, in patients with chronic PAD and CAD. Although the vascular dose of Xarelto in the COMPASS trial was associated with a higher rate of major bleeding, there were no significant differences in the rates of fatal bleeding, intracranial hemorrhage, or symptomatic bleeding in a critical organ.

Note: The original text has been abridged.

Source: U.S. FDA approves expansion of the peripheral artery disease (PAD) indication for Xarelto™ plus aspirin

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