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

On October 12, the Center for Drug Evaluation (CDE) announced its proposal to include three drugs in the priority review and approval program, on the grounds that they are “new varieties, dosage forms, and strengths of pediatric medicines that align with children’s physiological characteristics.” The three drugs are Bayer’s “Rivaroxaban Granules” (JXHS2000148/9), “Rivaroxaban for Oral Suspension” (no acceptance number 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. The tablet formulation was first launched 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.

Bayer submitted a marketing application for rivaroxaban granules on September 25, 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 full-term neonates, infants, children, and adolescents under 18 years of age after initiation of standard anticoagulant therapy.”

In the pediatric population, venous thromboembolism (VTE) is a relatively rare condition, with an incidence approximately 100-fold 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 developed by Sanofi that targets IL-4Rα. In March 2017, it received FDA approval as the first targeted biologic agent for the treatment of moderate-to-severe atopic dermatitis in adults. On June 17, 2020, it was approved in China for the treatment of moderate-to-severe atopic dermatitis in adults.

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 topical prescription medications are not advisable.” This represents the second indication for dupilumab.

Dupilumab (Dupixent®) binds to IL-4Rα, 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 additional approvals for asthma and nasal polyps indications, reaching $924 million in sales in 2018. In 2019, its global sales amounted to $2.313 billion, representing a significant increase of 150%.

Atopic dermatitis is a common, recurrent, chronic inflammatory skin disease. Patients typically present with chronic rashes characterized by inflammation and pruritus. Patients with moderate-to-severe atopic dermatitis often have widespread erythematous rashes covering the majority of their body surface area, leading to intense, persistent pruritus, xerosis, 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 restricted. Topical therapies, such as corticosteroids, have limited efficacy in 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.