October 28, 2020
Bayer’s development partner, Janssen Research & Development,
LLC, has submitted a supplemental New Drug Application (sNDA)
to the US Food and Drug Administration (FDA) for a new
indication to expand the use of Xarelto (rivaroxaban) in
people with peripheral artery disease (PAD) to include
those after recent lower-extremity revascularization due
to symptomatic PAD.
They showed that Xarelto vascular dose (2.5 mg twice daily)
plus aspirin (100 mg once daily) was superior to aspirin
alone in reducing the primary efficacy endpoint; a composite
of acute limb ischemia, major amputation of a vascular
etiology, heart attack, ischemic stroke or cardiovascular
death, with similar rates of Thrombolysis in Myocardial
Infarction (TIMI) major bleeding.
Two major phase III trials - VOYAGER PAD and COMPASS -
have now evaluated the use of dual antithrombotic
pathway inhibition with Xarelto in combination with aspirin
in more than 14,000 patients with PAD. Xarelto, in
combination with aspirin, was approved by the US FDA in
2018 to reduce the risk of major cardiovascular (CV)
events in patients with chronic PAD and coronary artery
disease (CAD). It is the only direct oral anticoagulant
(DOAC) approved for use in these patients.
The VOYAGER PAD trial is the first to demonstrate the
benefits of dual pathway inhibition in patients with
symptomatic PAD post revascularization, for whom there
are currently limited treatment options and no Class I
Guideline recommended treatment.
“By demonstrating the efficacy of dual pathway inhibition
in patients with PAD who have recently undergone a
revascularization procedure, the VOYAGER PAD study results
reinforce the benefits of Xarelto in patients with PAD,”
said Dr Joerg Moeller, member of the Executive Committee
at Bayer AG’s Pharmaceuticals Division and Head of Research
PAD is caused by atherosclerosis, a chronic progressive
disease, which is characterized by a build-up of plaque
in the arteries limiting blood flow to the limbs. It is
a serious underlying health crisis that impacts an estimated
20 million Americans with only 8.5 million diagnosed.
PAD increases the risk for major CV events and is the
leading cause of amputation which can double a patient’s
risk of death.
In Europe, Bayer had submitted a variation to include the
VOYAGER PAD data in the label of Xarelto in August 2020.
The treatment of patients with symptomatic PAD at high
risk for ischaemic events is already approved for Xarelto
when co-administered with aspirin. The VOYAGER PAD study
proves the benefits of Xarelto in patients with symptomatic
PAD after lower-extremity revascularization.
The phase III VOYAGER PAD study included 6,564 patients
from 542 sites across 34 countries worldwide.
In the study, patients were randomized to receive either
Xarelto 2.5 mg twice daily plus aspirin 100 mg once daily
or aspirin 100 mg once daily alone. The primary efficacy
endpoint was a composite of acute limb ischemia, major
amputation of a vascular etiology, heart attack (myocardial
infarction, MI), ischemic stroke or cardiovascular death.
The primary safety outcome was major bleeding according to
the Thrombolysis in Myocardial Infarction (TIMI) classification.
Xarelto is approved in more than 130 countries, whilst the
approved labeling, including the number of indications may
differ from country to country.
Rivaroxaban was discovered by Bayer, and is being jointly
developed with Janssen Research & Development, LLC. Xarelto
is marketed outside the US by Bayer and in the US by Janssen
Pharmaceuticals, Inc. (Janssen Research & Development, LLC and
Janssen Pharmaceuticals, Inc. are part of the Janssen
Pharmaceutical Companies of Johnson & Johnson).