Three Pediatric Medicines—Rivaroxaban Granules, Rivaroxaban for Oral Suspension, and Dupilumab Injection—Proposed for Priority Review in China

October 12, CDEPublic Notice: Proposal to Include Three Drugs in the Priority Review and Approval Program, on the Grounds of Being “New Varieties, Dosage Forms, and Strengths of Pediatric Drugs That Align with Children’s Physiological Characteristics.” The three drugs are Bayer’s “Rivaroxaban Granules” (JXHS2000148/9), “Rivaroxaban for Oral Suspension” (no application number assigned yet), and Sanofi’s “Dupilumab Injection” (JXSS2000035).

Rivaroxaban Granules/for Oral Suspension

Rivaroxaban is a non-vitamin K antagonist oral anticoagulant jointly developed by Bayer and Janssen. Its dosage forms include tablets, capsules, granules, and suspensions. Among these, the tablet formulation was first marketed in China in 2009 under the brand name Xarelto®. To date, it has been approved for five indications, and five generic versions have received approval, manufactured by Chia Tai Tianqing Pharmaceutical Group, CSPC Pharmaceutical Group, Yangtze River Pharmaceutical Group, Nanjing Chia Tai Tianqing Pharmaceutical, and Jiangsu Jiayi Pharmaceutical. Only Bayer has submitted marketing applications for the granule and suspension formulations.

On September 25, Bayer submitted a marketing application for rivaroxaban granules, which was accepted by the Center for Drug Evaluation (CDE). The indication proposed for inclusion in the priority review is “for the treatment of venous thromboembolism (VTE) and prevention of VTE recurrence in term neonates, infants, children, and adolescents under 18 years of age after initiation of standard anticoagulant therapy.”

Venous thromboembolism (VTE) is a relatively rare condition in the pediatric population, with an incidence approximately 100 times lower than that in adults. Currently, the treatment of VTE in children is primarily based on extrapolations from adult studies. Therefore, there remains an unmet need for novel anticoagulant regimens tailored to pediatric patients with VTE.

Dupilumab Injection

Dupilumab is a human monoclonal antibody targeting IL-4Rα, developed by Sanofi. In March 2017, it became the first targeted biologic approved by the FDA for the treatment of moderate-to-severe atopic dermatitis in adults. On June 17, 2020, it was approved in China for the same indication.

The indication proposed for inclusion in the priority review is “for the treatment of moderate-to-severe atopic dermatitis in adolescents aged 12 years and older and adults whose disease is inadequately controlled with topical prescription medications, or for whom use of topical prescription medications is not advisable,” which represents the second indication for dupilumab.

Dupilumab (Dupixent®) binds to IL-4Rα, thereby simultaneously blocking the IL-4 and IL-13 signaling pathways; IL-4 and IL-13 are considered the key drivers of persistent inflammation in atopic dermatitis.

On March 28, 2017, Dupixent® received FDA approval for market launch, becoming the first biologic agent approved for the treatment of moderate-to-severe atopic dermatitis, and achieved sales of $251 million in its first year on the market. Subsequently, Dupixent gained approval for additional indications, including asthma and nasal polyps. In 2018, it generated $924 million in sales. In 2019, its global sales reached $2.313 billion, representing a substantial increase of 150%.

Atopic dermatitis is a common, recurrent, chronic inflammatory skin disease, typically characterized by chronic rashes with inflammation and pruritus. Patients with moderate-to-severe atopic dermatitis often present with widespread erythematous rash covering most of the body, leading to intense and persistent pruritus, dry skin, crusting, and exudation, while therapeutic options remain very limited.

Currently, there is limited data on patients with atopic dermatitis in China. Publicly available data indicate that the prevalence of atopic dermatitis among children was nearly 13% in 2016. However, therapeutic options for moderate-to-severe atopic dermatitis in China are highly constrained. Topical therapies, such as corticosteroids, offer limited efficacy for patients with moderate-to-severe disease and are difficult to use long-term, while systemic treatments, including immunosuppressants or oral glucocorticoids, may lead to serious adverse effects.