Bemiltenase Alfa (Bojia Ning®): A Global First-in-Class Factor X Activator for Hemophilia Patients with High-Titer Inhibitors

The development of neutralizing inhibitors against coagulation factors is the most severe and difficult-to-manage immune-related complication during replacement therapy for hemophilia. Among these,High-titer inhibitors (>5BU）Patient RoutineComplete loss of efficacy of FⅧ/FⅨ infusion, recurrent spontaneous bleeding, joint disability, and a significantly increased risk of death from severe hemorrhage. According toWorld Federation of Hemophilia (WFH) "Inhibitors to Clotting Factor" guidelines describe:High-titer inhibitors (>5B) Patients who do not respond to standard coagulation factor infusion, experience frequent spontaneous bleeding, rapid progression of arthropathy, and an increased risk of fatal bleeding and death; therefore, inhibitors are one of the most serious complications in hemophilia treatment.

For a long time, patients with hemophilia inhibitors have faced multiple unmet needs:Limited clinical treatment options, global lack of approved drugs in this field, incomplete subtype coverage, and heavy economic burden。StaidsonDeveloped by Jiangsu Beijietai Biotechnology, a controlled subsidiaryPomitase for Injectionα (Brand Name: Bojianing®), as the world's first coagulation factorX (FX) activator, a Class 1 innovative biologic drug in China, received conditional marketing approval from the NMPA on June 4, 2026, specifically forInhibitors>Hemorrhage Treatment for Adult Patients with Congenital Hemophilia A/B in 5BU。

Hemophilia with High-Titer Inhibitors:

The Most Challenging Diagnostic and Therapeutic Dilemmas in Clinical Practice

Inhibition of Influenza Epidemiology and Disease Hazards

Inhibitors are infused exogenousIgG-type neutralizing antibodies produced by the body after FⅧ/FⅨ administration are also a core refractory complication of hemophilia.

Epidemiological data show:

Severe HemophiliaA The incidence of inhibitor development in patients was20%~30%

HemophiliaB The incidence of inhibitors in patients was only1.5%~3%

PressBethesda Titer Classification,＞5BU is defined as a high-titer inhibitor

High-titer inhibitors account for approximately of all inhibitor patients75%

Such patients may experience complete failure of routine coagulation factor replacement therapy.

Core Clinical Burden in Patients with High-Titer Inhibitors

According to the Chinese Guidelines for the Diagnosis and Treatment of Hemophilia with Inhibitors (2023 Edition), patients with high-titer inhibitors (Bethesda titer >5 BU) may experience complete failure of conventional clotting factor replacement therapy, representing the most challenging population to manage clinically and those with the poorest prognosis in hemophilia care.

Core Diagnostic and Therapeutic Challenges Are Primarily Divided Into:

1. Hemorrhage is difficult to control, with a significantly increased risk of disability and mortality

According to the "Chinese Guidelines for the Diagnosis and Treatment of Hemophilia with Inhibitors ("2023 Edition)》, patients with high-titer inhibitors respond poorly or ineffectively to conventional clotting factor therapy, failing to control bleeding; life-threatening hemorrhage is the primary cause of death in such patients.

2. Limited options for inhibitor eradication, resulting in modest overall treatment benefits

Implementing immune tolerance induction (ITI) requires patients to undergo frequent venipuncture and receive high doses of clotting factor concentrates; both treatment costs and patient adherence can impact the success rate of ITI. Furthermore, the success rate of ITI in hemophilia B patients with inhibitors is only 30%, accompanied by risks of allergic reactions and irreversible renal injury. Therefore, ITI should be undertaken with caution in hemophilia B patients with inhibitors.

3. Existing clinical therapeutic drugs have inherent limitations and cannot meet the needs of all scenarios.

Existing interventions are limited by narrow indications, elevated safety risks, and an inability to cover all patient subtypes, making them particularly unsuitable for hemophilia.Therapeutic Needs in Patients with Hemophilia B and Inhibitors: Significant Gaps Remain in the Emergency Management of Breakthrough Bleeding.

4. Global innovation fills a long-standing therapeutic gap, addressing insufficient accessibility of medications at the primary care level

Currently, imported drugs such as recombinant activated factor VII (rFVIIa) and bispecific prophylactic antibodies are available internationally to manage bleeding in hemophilia patients with high-titer inhibitors. However, there is a lack of a comprehensive, domestically developed, and independently innovative treatment system in both China and abroad that fully covers patients with inhibitors in hemophilia A and B. At present, mainstream clinical practices in China rely heavily on imported medications, resulting in persistently high treatment costs and limited patient access to therapy. Furthermore, inadequate supportive care capabilities at primary healthcare institutions hinder the standardized and routine management of acute bleeding episodes, leading to a significant unmet clinical need.

Bojia Ning® World’s first mechanism of action:

Completely Bypass Inhibitor Interference

The intrinsic coagulation pathway relies on the FVIII-FIX complex to efficiently activate FX, generating a coagulation amplification effect. In patients with high-titer inhibitors, neutralizing antibodies against FVIII or FIX completely block this intrinsic coagulation amplification pathway. Traditional bypassing agents can only initiate the coagulation cascade indirectly and passively; they fail to reconstruct the unique coagulation amplification efficacy of the intrinsic pathway. Due to limitations in their mechanism of action, these agents inherently suffer from suboptimal hemostatic efficacy, significant variability in treatment response, and a high tendency for recurrent bleeding. Bojianing®, independently developed by Staidson, is the world’s first FX-specific activator. It directly and potently activates FX, restoring the complete coagulation amplification response without any dependence on the FVIII/FIX pathway. This innovative mechanism overcomes the inherent drawbacks of traditional bypassing agents, offering stable hemostasis and a low rate of bleeding recurrence. Furthermore, it is equally applicable to patients with either hemophilia A or hemophilia B who have high-titer inhibitors.

Bojianing®’s hemostatic mechanism is entirely independent of FⅧ and FⅨ molecules.

Therefore, in vivo inhibitors (anti-FⅧ, anti-FⅨ neutralizing antibodies) cannot exert an inhibitory effect on it.

This means:

HemophiliaA. For patients with high-titer inhibitors

HemophiliaB. Applicable to patients with high-titer inhibitors

Remains effective after failure of conventional factor infusion

FillThe Gap in Domestic Emergency Drugs Specifically for Type B Inhibitors

Bojia Ning® Multicenter Clinical Evidence-Based Data: Dual Advantages in Efficacy and Safety

According to Bojianing® Core Efficacy Data from Pivotal Clinical Studies: Pivotal Clinical Study (IIPhase b) included adult patients with hemophilia A or B and high-titer inhibitors. The unified dosing regimen was 0.10 U/kg, repeatable every 4 hours until hemostasis was achieved. Meanwhile, the primary endpoint of the 12-hour effective hemostasis rate was 81.94%, significantly superior to the pre-specified single-arm target value of 55%. P < 0.0001, indicating a statistically significant difference.

Stratified Efficacy

Initial Bleeding12-Hour Hemostasis Efficacy Rate: 88.00%

Target Joint Hemorrhage12-Hour Effective Hemostasis Rate: 86.96%

HemophiliaNo difference in effective hemostasis rate between patients A and B

This indicates that Bojianing® Demonstrates significant clinical value in patients with hemophilia A and B accompanied by high-titer inhibitors.

Convenience of Administration

77.12% of bleeding events were stabilized with hemostasis achieved after only 1–2 intravenous administrations.

The average number of administrations is only1.9 ± 0.7 times.

andCompared with rFⅦa, the frequency of administration is significantly reduced; Bojia Ning® can significantly alleviate the pain associated with repeated intravenous injections and improve treatment compliance.

High-Dose Data

Phase Ib/II data show that the hemostasis rate in the high-dose group (0.16 U/kg) can reach 96.48%. This provides a higher dosing option for severe bleeding, trauma, or major postoperative hemorrhage.

Complete Safety Evidence from Clinical Trials

Based onI. Summary of Cumulative Subject Safety in Phase Ib/II and IIb Trials: Bojianing® Demonstrated a Favorable Overall Safety Profile.

Primary Safety Outcomes

NoneGrade 3 or Higher Drug-Related Adverse Events

No drug-related serious adverse events occurred (SAE）

Approx.36% of subjects experienced Grade 1 mild adverse reactions

Most adverse reactions do not require intervention and resolve spontaneously.

No thromboembolic events occurred in all clinical trials.

The risk of immunogenicity is extremely low, and the follow-up results from clinical trials at various stages show that,No anti-drug antibodies (ADA) were detected in any subjects, with no drug-related immune responses or neutralizing antibody production., without compromising hemostatic efficacy, and no allergic or immune-related adverse events.

This means:

Supports long-term, repeated treatment for bleeding.

Low propensity for the development of neutralizing antibodies against the drug itself

Offers long-term management value for patients with recurrent bleeding

In summary, from a clinical perspective, Bojianing® effectively complements the inhibitor bleeding treatment system recommended by the Chinese Guidelines for the Diagnosis and Treatment of Hemophilia with Inhibitors (2023 Edition), addressing the clinical limitations of traditional therapies. From an industrial standpoint, this drug has achieved a global innovative breakthrough in the acute bleeding treatment of hemophilia patients with high-titer inhibitors, breaking the monopoly held by imported drugs. Furthermore, leveraging mid-to-long-term indication expansion and systematic collaborative layout within its pipeline, Bojianing® possesses irreplaceable clinical value and promising prospects for global industrialization, holding the potential to significantly improve the treatment landscape and quality of life for hemophilia patients with inhibitors worldwide.

References: Thrombosis and Hemostasis Group, Hematology Branch, Chinese Medical Association, China HemophiliaCollaborative Group on Hemophilia. Diagnosis and Treatment of Hemophilia Complicated by InhibitorsNationalGuidelines (2023 Edition) [J]. Chinese Journal of Hematology, 2023, 44(11):881-892.

Chinese Guidelines for the Treatment of Hemophilia (2020 Edition)Chinese Journal of Hematology, 2020,41

About Staidson:

The Company’s core business focuses on the research and development, manufacturing, and marketing of innovative drugs with independent intellectual property rights, particularly biopharmaceuticals. According to the industry classification for listed companies by the China Securities Regulatory Commission (CSRC), it falls under the category “C27 Pharmaceutical Manufacturing.” As an innovative biopharmaceutical enterprise, the Company boasts a complete industrial chain with well-established systems for R&D, production, quality management, marketing, and supporting operations, and is recognized as a National High-Tech Enterprise.

The company is dedicated to the research and development, production, and sales of therapeutic drugs addressing unmet clinical needs, primarily including protein-based drugs (including therapeutic monoclonal antibody drugs) and chemical drugs. Its therapeutic focus areas include infectious diseases, respiratory and critical care, autoimmune diseases, and neurological disorders.