Table 1.

Exploration of new targets or pharmaceutical technologies for treating hemophilia

Product type/name	Patient population Target	Trial No.	Administration method Frequency	Latest clinical results	References
Antibody
Marstacimab	PwHA and PwHB with and without inhibitors TFPI	NCT03363321	Subcutaneous Once-weekly	FDA has approved marstacimab for PwHA or PwHB without inhibitors, and the BASIS clinical trial for marstacimab in inhibitor-positive PwH, as well as the BASIS KIDS clinical trial in children aged 1 to <18 years with or without inhibitors, are both ongoing.	Pfizer87 and Matino et al.89
SR604	PwHA and PwHB with and without inhibitors APC	NCT06349473; CTR20241608 (CDE)	Subcutaneous Once every 2 weeks (tentative)	SR604 exhibited prophylactic and therapeutic efficacy in tail-bleeding and knee-injury mouse models of HA and HB expressing human APC (pre-clinical). CDE has approved SR604 for phase I clinical trials.	Jiang et al.126 and CDE127
Recombinase
SerpinPC	PwHA and PwHB APC	NCT04073498; NCT05789524; NCT05789537	Subcutaneous Once every 2 or 4 weeks	SerpinPC treatment reduced the median all-bleed ABR to 1.0, representing a 96% reduction from the pre-exposure baseline ABR (phase I/IIa). A phase II clinical trial is underway.	Baglin et al.95 and Centessa Pharmaceuticals128
Cellular gene therapy
Auto CD34+ cells transduced with LV to produce FVIII	PwHA without inhibitors FVIII	NCT03818763	Intravenous Only once	No reports of spontaneous bleeding or a need for “on-demand” factor VIII post-infusion following the demonstration of whole blood vector copy number (phase I).	Wilcox et al.129
BE-101 (autologous primary human B cells medicine engineered to insert the human FIX gene)	PwHB FIX	Pre-clinical	Intravenous Unknown	A single dose of BE-101 could achieve active and sustained FIX levels. The data confirmed the expected biodistribution of FIX-expressing B cells in bone marrow tissue, where they engrafted stably over time (pre-clinical). FDA has approved BE-101 to conduct phase I/II clinical trials.	Be Biopharma 130
SiRNA
Fitusiran	PwHA and PwHB with and without inhibitors Antithrombin	NCT03417245; NCT03417102	Subcutaneous Once-monthly	Fitusiran prophylaxis showed hemostatic efficacy and statistically significant reductions in ABR (phase III).	Young et.al.131and Srivastava et al.132

ABR, annualized bleeding rate; APC, activated protein C; CDE, the Center for Drug Evaluation of the China National Medical Products Administration; CFCs, coagulation factor concentrates; FDA, US Food and Drug Administration; FIX, factor IX; FVIII, coagulation factor VIII; HA, hemophilia A; HB, hemophilia B; LV, lentiviral vector; PwHA, patients with hemophilia A; PwHB, patients with hemophilia B; siRNA, small interfering RNA; TFPI, tissue factor pathway inhibitor.