Bayer's Rivaroxaban for Oral Suspension Approved in China for Pediatric VTE Treatment and Prevention

Today, the official website of China's National Medical Products Administration (NMPA) announced that the new drug application for Bayer's Rivaroxaban Dry Suspension has been officially approved. According to the priority review announcement by the Center for Drug Evaluation (CDE) under the NMPA, the application is indicated for: the treatment of venous thromboembolism (VTE) and prevention of VTE recurrence in full-term newborns, infants, children, and adolescent patients under 18 years old following the initiation of standard anticoagulation therapy.

Screenshot source: NMPA official website

Rivaroxaban was discovered by Bayer and is currently being co-developed by Bayer and Janssen, a subsidiary of Johnson & Johnson. It is an orally administered drug that selectively and directly inhibits Factor Xa. By inhibiting Factor Xa, it interrupts the intrinsic and extrinsic pathways of the coagulation cascade, suppressing thrombin generation and thrombus formation. Additionally, rivaroxaban does not inhibit thrombin (activated Factor II) and has not been shown to affect platelets.

In China, Rivaroxaban Tablets (trade name: Xarelto) have been approved for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery, adult patients with venous thromboembolism, adult patients with non-valvular atrial fibrillation, and patients with chronic coronary artery disease or peripheral artery disease, among other indications. In March 2022, Rivaroxaban Tablets were approved in China for a new indication, for the treatment of venous thromboembolism and prevention of recurrent venous thromboembolism in children and adolescents under 18 years of age weighing between 30kg to 50kg and 50kg or more, following at least 5 days of initial non-oral anticoagulation therapy.

The product approved for marketing in China this time is Rivaroxaban Dry Suspension. The marketing application was accepted by the CDE in September 2020 and was included in the priority review by the CDE on the grounds of "new varieties, dosage forms, and specifications of pediatric drugs that meet the physiological characteristics of children." Studies have shown that, compared with tablets, dry suspensions have advantages such as better absorption and convenient administration, offering better compliance for special populations such as children and the elderly.

Screenshot source: CDE official website

Previously, results from a Phase 3 clinical study named EINSTEIN-Jr showed that rivaroxaban demonstrated strong efficacy and safety in pediatric patients with venous thrombosis, with results similar to those previously obtained in adults. Compared with standard treatment (heparin alone or combined with vitamin K antagonists), the recurrence rate of venous thrombosis in children using rivaroxaban was lower, and no major bleeding events occurred in the rivaroxaban group. This indicates that the efficacy and safety of rivaroxaban in pediatric patients with venous thrombosis are consistent with previous findings in adult studies.

Venous thrombosis includes cerebral venous sinus thrombosis (clots in the brain), pulmonary embolism (clots migrating to the lungs), and deep vein thrombosis, which typically occurs in the deep veins of the legs. Venous thrombosis is a common complication among hospitalized pediatric patients. Currently recommended therapies for venous thrombosis include unfractionated heparin, low molecular weight heparin, and fondaparinux, with or without vitamin K antagonists.

References:

[1] Information on Pending Drug Approval Documents Released on May 7, 2022. Retrieved May 7, 2022. From https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20220507125048169.html

[2] Breaking News | Bayer's Xarelto® Approved in China for Patients with Coronary Artery Disease or Peripheral Artery Disease. Retrieved Aug 3, 2020, from https://mp.weixin.qq.com/s/ngwKFKB7C4w71pDzFJrCtw

[3] Phase III clinical trial results show that rivaroxaban is safe and effective for the treatment of venous thromboembolism in children. Retrieved Jul 15, 2019, from https://mp.weixin.qq.com/s/7lF6Tf2pv1o1R4L7ykTdGQ