Pharmaceutical Companies Intensify Competition in Hemophilia Therapeutics with Multiple Drug Advances

　　【Pharmaceutical Network Industry Dynamics】 Hemophilia is a hereditary bleeding disorder, primarily caused by the deficiency or abnormality of coagulation factor VIII or coagulation factor IX, leading to impaired blood clotting function in patients. Data shows that the global number of hemophilia patients is approximately 700,000. In China, according to relevant data, there were 121,600 patients with type A hemophilia and 21,500 patients with type B hemophilia in 2022, totaling 143,100 patients. It is estimated that by 2030, the number of hemophilia patients in China will increase to 145,800.
 

In order to better meet the medication needs of patients, many pharmaceutical companies have launched competition in the hemophilia field. It is reported that Emicizumab (艾美赛珠单抗), a bispecific antibody drug developed by Roche, was approved by the FDA for marketing in November 2017, becoming the first non-factor drug for the treatment of Hemophilia A, reducing the dosing frequency to once a week and improving patient compliance. Meanwhile, RoctavianTM (Valoctocogene Roxaparvovec), an AAV gene therapy under BioMarin Pharmaceutical, was approved by the EU in August 2022 for the treatment of severe Hemophilia A patients without a history of Factor VIII inhibitors and without detectable antibodies to AAV5.
 

In addition, there are currently multiple new hemophilia drugs worldwide in Phase III clinical trials and the marketing application stage, with drug types covering recombinant factor VIII, gene therapy, siRNA, bispecific antibodies, and monoclonal antibodies.
 

It was reported that, on June 27, Pfizer announced that the U.S. Food and Drug Administration (FDA) has accepted and granted priority review for the Biologics License Application (BLA) of its investigational gene therapy, fidanacogene elaparvovec, with an FDA action date (FDUFA) set for Q2 2024.
 

According to reports, Pfizer's submission of this marketing application is based on the efficacy and safety data from the Phase 3 BENEGENE-2 trial, which enrolled a total of 45 patients. The analysis showed that the BENEGENE-2 trial met its primary endpoint, meaning that compared with the FIX prophylactic treatment regimen, after infusion of fidanacogene elaparvovec, the annualized bleeding rate (ABR) for total bleeding events in patients achieved both non-inferiority and superiority.
 

On June 26 local time, Danish multinational pharmaceutical company Novo Nordisk (NVO.US) presented the phase 3 clinical trial data (explorer8) of its hemophilia therapy Concizumab at the 24th annual meeting of the International Society on Thrombosis and Haemostasis (ISTH): The trial included 148 hemophilia patients who had not used inhibitors, and results showed that the therapy reduced spontaneous and traumatic bleeding by 86% in hemophilia A patients and by 79% in hemophilia B patients.
 

Data show that Concizumab is an antibody against tissue factor pathway inhibitor (TFPI). TFPI is an anticoagulant protein that controls the initiation phase of coagulation, weakening the extrinsic coagulation pathway by inhibiting the formation of the FVIIa-TF-FXa complex.
 

Industry insiders pointed out that Pfizer has taken the lead in the anti-TFPI drug track. On May 31, Pfizer announced that its Marstacimab, for treating Hemophilia A and Hemophilia B, had reached the primary endpoint in a Phase 3 clinical trial. Compared with on-demand intravenous injection of clotting factors, Marstacimab reduced the annual bleeding rate (ABR) by 92% in patients. Compared with prophylactic treatment using clotting factors, Marstacimab reduced the annual bleeding rate by 35% in patients.
 

It is reported that Pfizer has laid out six products in the hemophilia field. Apart from the three marketed coagulation factor drugs, the remaining three (fidanacogene elaparvovec, giroctocogene fitelparvovec, and marstacimab) are all in the late-stage research phase. In addition to the aforementioned fidanacogene elaparvovec and marstacimab, giroctocogene fitelparvovec is a gene therapy for hemophilia A, and its pivotal Phase III clinical trial is expected to be completed by July 2024.
 

In addition, in the Chinese market, there has been new progress recently regarding hemophilia drugs. According to reports, on June 28, based on the announcement by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration, the hemophilia A gene therapy product ZS802 injection developed by Zhishan Weixin has received tacit approval for clinical trials and will soon commence phase 1/2 clinical trials. Previously, the company's hemophilia B gene therapy project had already been approved for clinical trials in China.
 

Data shows that ZS802 belongs to Class 1 new drugs developed by Zhishan Weixin. The features of this product include: 1) Utilizing a liver-specific ultra-small promoter independently developed by Zhishan Weixin, which solves the viral vector packaging challenge and significantly improves drug quality; 2) Incorporating an optimized coagulation Factor VIII sequence independently modified by Zhishan Weixin, enhancing drug activity through specific amino acid residue mutations; 3) Selecting the optimal serotype of the viral vector based on the characteristics of the Chinese population, ensuring more patients receive effective treatment.
 

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