Rivaroxaban, a Multi-Billion-Dollar Anticoagulant, Faces Patent Expiry in 2020

Compiled by: Yaowang

Blockbuster Drug BenefitsVasaban FormulationThe patent has been declared invalid.

# Major Drug Formulation Patent Invalidated

Recently, the China National Intellectual Property Administration issued a decision on the examination of a request for invalidation, declaring the patent “Method for Preparing Solid Pharmaceutical Compositions for Oral Administration” (Application/Patent No.: 200480035106.X) held by Bayer Intellectual Property GmbH as “wholly invalidated.”

The claims are as follows:

According to the investigation, the technology described in the patent involves a special surface treatment of rivaroxaban during the wet granulation stage, which improves absorption properties and significantly enhances the bioavailability of the resulting formulation. The wetting agent used is sodium lauryl sulfate, and hydroxypropyl methylcellulose serves as the hydrophilic binder.

Comments have pointed out that the invalidation of formulation patents is a normal occurrence, as the patent in question pertains to a wet granulation process, which is relatively common.

The compound patent expires next year.

In this instance, a formulation patent for rivaroxaban was declared invalid. Additionally, the compound patent for rivaroxaban is set to expire in 2020.

Publicly available information indicates that rivaroxaban tablets were jointly developed by Bayer and Janssen, and are primarily indicated for the prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery.

Rivaroxaban Tablets were approved for marketing by the European Medicines Agency (EMA) on September 30, 2008, and received FDA approval for launch in the United States on July 1, 2011.

In the domestic market, Bayer’s rivaroxaban (brand name: Xarelto) entered China in June 2009 for the prevention of venous thromboembolism in adults following elective total hip or knee replacement surgery.

In May 2015, two new indications for rivaroxaban tablets were approved by the China Food and Drug Administration (CFDA): treatment and prevention of deep vein thrombosis and prevention of pulmonary embolism, as well as stroke prevention in patients with atrial fibrillation.

Currently, only the original research product is marketed and sold in China. It is reported that rivaroxaban is a Class B drug listed in the 2017 National Reimbursement Drug List, restricted to patients with non-valvular atrial fibrillation who have poor control with warfarin therapy or are at high risk of bleeding, as well as patients undergoing lower limb joint replacement surgery.

In 2018, the sales revenue of rivaroxaban in the Chinese hospital market was approximately RMB 1.527 billion.

Since its market launch, rivaroxaban has demonstrated strong market performance, ranking second in sales among global cardiovascular drugs in 2017, surpassed only by apixaban tablets.

In 2018, Bayer’s sales of rivaroxaban amounted to €3,631 million, and Johnson & Johnson’s sales totaled $2,477 million, with the combined equivalent reaching approximately RMB 44.71 billion.

Fierce Competition in the Domestic Generic Drug Market

Rivaroxaban Compound Patent Expiring Soon, Domestic Generic Drug Competition Intensifying. The Yaozhi Drug Registration and Acceptance Database shows that there are as many as 63 acceptance numbers for rivaroxaban generic drug applications; among the 42 acceptance numbers filed under the old Class 6 category, 40 have already been approved for clinical trials. There are 21 acceptance numbers filed under the new Class 4 generic drug category, involving 15 companies, including Huahai, Chia Tai Tianqing, CSPC Ouyi, Yangzijiang, and others.

According to the latest review and approval information, on May 13, Suzhou No. 3 Pharmaceutical Factory's "Rivaroxaban Tablets" were shown as "under approval," potentially entering the approval stage first and becoming the first generic approved.

Shortly thereafter, on May 23, Zhejiang Huahai Pharmaceutical Co., Ltd. announced that it had received notification from the U.S. Food and Drug Administration (FDA) that its Abbreviated New Drug Application (ANDA) for Rivaroxaban Tablets had been granted tentative approval. (Tentative approval refers to an approval status granted by the FDA when all regulatory review requirements for a generic drug have been met, but final approval is withheld due to unexpired patents or exclusivity rights.)

According to the announcement, Huahai has invested approximately RMB 14.7005 million in research and development expenses for the rivaroxaban tablet project.

Rivaroxaban Tablets are one of Bayer’s best-selling drugs globally, with revenue surpassing the $1 billion mark in the first quarter of 2019, reaching €937 million ($1.043 billion). However, as the compound patent expires, Bayer will face competition from a host of generic drug manufacturers.

Appendix: Claims

Original Title: Billion-Dollar Blockbuster Drug, Patent Expiring Soon