Hemophilia B is an X-linked congenital bleeding disorder caused by a deficiency of coagulation factor IX (FIX) clotting activity, which can manifest as bruising, spontaneous bleeding events, or excessive bleeding after an injury or surgery, particularly into muscles, joints, and soft tissues [1, 2]. Hemophilia B accounts for up to 20% of all cases of hemophilia [1].

According to a World Federation of Hemophilia (WFH) global survey, in 2020, India had 3150 individuals with hemophilia B (incidence: 0.23 per 100,000), second only to the United States (n = 4093; incidence: 1.25 per 100,000) [3]. However, the actual incidence rate in India is probably higher than the rate reported by the WFH. In India, a substantial proportion of individuals with hemophilia remain undiagnosed, with many cases unregistered, suggesting that these rates are likely underestimated [4]. By comparison, the proportion of individuals with hemophilia B in 2020 was approximately 10-fold lower in other Asian countries, including Indonesia (n = 347; incidence of 0.13 per 100,000), the Philippines (n = 201; 0.19 per 100,000), Thailand (n = 206; 0.30 per 100,000), and Malaysia (n = 177; 0.55 per 100,000) [3]. Given the poor availability of diagnostic facilities, a diagnosis of hemophilia can be missed leading to a low rate of diagnosis and/or late diagnosis so by the time of diagnosis, Indians with hemophilia may have accrued joint damage due to the lack of treatment in the absence of a diagnosis [4].

Available treatment options for individuals with hemophilia B include plasma-derived or recombinant clotting factor concentrate, administered on demand or as prophylaxis treatment [1, 5]. Although current plasma-derived products have a good safety profile, concerns remain regarding the potential for transmission of infectious diseases; this has led to a transition toward greater use of recombinant products [1, 5]. However, the requirement for multiple infusions of factor replacement in some individuals can limit adherence and, thus, the efficacy of these therapies [5].

The use of both standard and extended half-life FIX replacement products is much lower per capita in India than in other parts of Asia and the rest of the world [3]; recent 2020 WFH estimates for mean per capita FIX use in 2019 were 0.015 IU/total population in India compared with estimates ranging from 0.0004 IU/total population in Indonesia to 0.400 IU/total population in Singapore, 1.575 in the United States, and 1.138 in the United Kingdom [3]. Economic considerations drive treatment decisions in Indians with hemophilia, with few individuals having access to factor replacement therapy and subsequent reliance on adjunct therapies such as tranexamic acid and products such as fresh frozen plasma and cryoprecipitate [4]. Development of inhibitors has also been reported in Indian patients with hemophilia, including those with hemophilia B, with prevalence rates of up to 13% [4]. Gaining an understanding of inhibitor development in these patients is hindered by the inconsistent administration of factor replacement therapy and frequent switching of products.

Nonacog alfa, a standard half-life recombinant human blood coagulation FIX replacement product, is approved in India for the treatment and prophylaxis of bleeding events in patients with hemophilia B [6, 7]. Although extended half-life replacement FIX products are available, access to these products is limited in India so the need for standard half-life products recombinant or plasma-derived products is still high. Therefore, this post-approval phase 4 study evaluated the safety and efficacy of nonacog alfa in males with moderately severe or severe hemophilia B in India.