Roche Submits Four NDAs for Emicizumab Injection in China, Seeking Priority Review for Expanded Indication in Hemophilia A

Reposted from | Medical Horizon

The latest public notice on the website of the Center for Drug Evaluation (CDE) under China’s National Medical Products Administration (NMPA) indicates that four New Drug Applications (NDAs) for emicizumab injection (Hemlibra), submitted by Roche, are proposed to be included in the priority review program. Emicizumab is a bispecific antibody that has previously been granted Breakthrough Therapy Designation and Priority Review status by the U.S. Food and Drug Administration (FDA). In China, emicizumab is listed among the urgently needed overseas new drugs and was approved for marketing in 2018 through the priority review and approval pathway for the treatment of hemophilia A.

According to the CDE announcement, the four New Drug Applications (NDAs) for emicizumab injection proposed for inclusion in the priority review correspond to four specifications: 60 mg (0.4 mL)/vial, 105 mg (0.7 mL)/vial, 150 mg (1 mL)/vial, and 30 mg (1 mL)/vial. The proposed indications are all for routine prophylactic treatment to prevent bleeding or reduce the frequency of bleeding episodes in adult and pediatric patients with hemophilia A (congenital factor VIII deficiency) without factor VIII inhibitors.

Source: CDE Official Website

Emicizumab is a bispecific antibody targeting factor IXa and factor X. It brings together factor IXa and factor X, which are required to activate the natural coagulation cascade, thereby helping patients with hemophilia A restore their coagulation function. This product was discovered by Chugai Pharmaceutical Co., Ltd., a subsidiary of Roche, and jointly developed by Chugai Pharmaceutical Co., Ltd., Roche, and Genentech.

In November 2017, emicizumab received its initial approval from the U.S. Food and Drug Administration (FDA) for market launch and has since been approved in numerous countries and regions worldwide. According to Roche’s financial reports, global sales of emicizumab reached CHF 1.38 billion (approximately USD 1.52 billion) in 2019. It is one of Roche’s key products and a blockbuster drug in the global hemophilia treatment landscape.

According to a press release previously issued by Roche, emicizumab is the first prophylactic therapy approved by the FDA for the treatment of hemophilia A in patients with or without factor VIII inhibitors. The approval of emicizumab for the indication in patients with hemophilia A without factor VIII inhibitors was primarily based on the results of the following two Phase 3 trials:

In the HAVEN 3 study, a total of 71 adolescents aged 12 years and older and adults with hemophilia A were divided into two groups: one group received emicizumab prophylaxis once weekly (n=36), and the other received it once every two weeks (n=35). The results showed that treated bleeding episodes were reduced by 96% and 97%, respectively, in the two groups. Furthermore, both groups demonstrated significant reductions across all bleeding-related endpoints compared to the no-prophylaxis group (n=18), with a favorable safety profile.

In the single-arm, Phase 3 HAVEN 4 study, a total of 41 patients with hemophilia A received prophylactic treatment every four weeks. Clinically meaningful bleeding control was achieved in both patients with factor VIII inhibitors (n=5) and those without factor VIII inhibitors (n=36), with a favorable safety profile.

In China, emicizumab is among the first batch of overseas new drugs designated as clinically urgent. The drug received accelerated approval from the National Medical Products Administration (NMPA) in China in November 2018 for routine prophylactic treatment to prevent bleeding or reduce the frequency of bleeding episodes in patients with hemophilia A (congenital factor VIII deficiency) with factor VIII inhibitors.

Emicizumab’s proposed inclusion in the priority review program in China indicates that the marketing application for its new indication is expected to receive accelerated approval, positioning it as a prophylactic agent for hemophilia A suitable for patients both with and without factor VIII inhibitors.

Hemophilia A is an X-linked recessive hereditary bleeding disorder caused by a deficiency of coagulation factor VIII and abnormal coagulation function. Patients' blood fails to clot normally, leading to uncontrolled, frequent, persistent, or spontaneous bleeding.

Currently, many prophylactic therapies for hemophilia A patients without factor VIII inhibitors require multiple injections per week. Even after administering the medication, patients may still experience bleeding episodes; therefore, there is an urgent need for new therapies to improve their quality of life. Emicizumab represents a significant breakthrough for the hemophilia A patient population, as it reduces bleeding events and allows for dosing intervals of once weekly, once every two weeks, or once every four weeks.

References:

[1] Center for Drug Evaluation, National Medical Products Administration of China. Retrieved Sep 14, 2020, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=21#

[2] FDA approves Roche’s Hemlibra for haemophilia A without factor VIII inhibitors. Retrieved October 5, 2018, from https://www.roche.com/media/releases/med-cor-2018-10-04c.htm

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