Actual therapeutic efficacy of recombinant DNA-derived coagulation factor VIII concentrate (recombinant)

Recombinant DNA-derived coagulation factor VIII concentrate (Altuiiio) was approved by the U.S. Food and Drug Administration (FDA) on February 23, 2023, becoming a first-of-its-kind highly sustained factor VIII replacement therapy. The drug is indicated for routine prophylaxis and as-needed treatment to control bleeding episodes in patients with hemophilia A, as well as for perioperative management in adults and children. As the first and only hemophilia A treatment that can be administered once weekly and maintain normal to near-normal levels (more than 40%) most of the time, Altuiiio has shown significant efficacy in bleeding control and has significant advantages in reducing bleeding compared with previous factor VIII preventive therapies.

The FDA's approval is based on data from the pivotal Phase 3 clinical study of XTEND-1 recently published in the New England Journal of Medicine. The study showed that once-weekly prophylactic treatment with Altuiiiio successfully met the primary endpoint, providing significant bleeding protection in patients with severe hemophilia A, with a mean annual bleeding rate (ABR) of 0.70 (95% CI: 0.5-1.0) and a median ABR of 0.0 (Q1, Q3: 0.0, 1.0). Compared with the patient's previous factor prevention treatment, Altuiiiio's ABR was significantly reduced by 77% (95% CI: 58%-87%), indicating its effectiveness and reliability in clinical application.

In addition, the research results also show thatAltuiiio is not only effective in preventing systemic bleeding, but also performs well in preventing joint bleeding. The median annualized joint bleeding rate was 0 (Q1, Q3: 0.0, 1.0), and for target joints (joints with recurrent bleeding, such as knees, ankles, or elbows), the bleeding relief rate reached 100%. Average factor VIII activity remained above 40% most of the time during Altuiiiio treatment, with activity above 10% on day 7. These activity levels were closely associated with a lower risk of bleeding.

Tolerability was also well assessed. In this study, Altuiiiio was considered well tolerated and no factor VIII production was detected, although this may occur after taking Altuiiiio. In addition, XTEND-Kids interim data showed that children under 12 years old (n=23) received once-weekly Altuiiiio treatment for 26 weeks, with an average ABR of 0.5 (95% CI: 0.2-1.3) and a median ABR of 0 (Q1, Q3: 0.0, 1.3), indicating that the effectiveness and safety of the drug in the pediatric population are equally satisfactory. Complete results from XTEND-Kids will be presented at a future medical meeting, further advancing understanding of the drug.

Regarding the safety ofAltuiiio, all study results show that its safety is confirmed. The most common side effects include headache and joint pain, with an incidence rate of more than 10%. Importantly, factor VIII antibodies have not been reported in patients taking Altuiiiio, although it is possible to develop antibodies following use of the drug.

To sum up,Altuiiio, as an innovative treatment for hemophilia A, has demonstrated significant efficacy and good safety in routine prevention, on-demand treatment and perioperative bleeding management. Its simple recommended dose is 50 IU/kg, which is suitable for all patients and different clinical situations, providing new hope and options for the treatment of hemophilia patients.

Reference link:https://www.drugs.com/history/altuviiio.html