Corifact (human coagulation factor XIII) / CSL Behring - LARVOL DELTA

Identifying the differences in the structural etiology underlying coagulation Factor XIII mutations based on a 2.68 Å cryo-EM structure of the coagulation Factor XIII-A2B2 complex. (ISTH 2024) - " Native plasma FXIII, isolated from Fibrogammin P, underwent cryo-EM analysis... Cryo-EM data analysis yielded a refined 2.68 Å resolution structure, revealing direct interactions between FXIII subunits, particularly through FXIII-B sushi domains 2, and FXIII-B dimerization onto FXIII-A2 dimers via sushi domain 5 (Figure 1). Heterozygous missense variants were strategically positioned closer to the complex interface than homozygous defects, suggesting a dominant-negative effect in heterozygous states. In a cohort of 17 patients, eight missense variants, including novel ones (I235F and R409L), were identified, located near the calcium-binding site and catalytic center."

F13A1 • F13B

A case of anti-NPX-2 antibody-positive dermatomyositis resulting in massive haemothorax with acquired factor XIII deficiency. (PubMed, Mod Rheumatol Case Rep) - "Emergency transcatheter arterial embolisation was performed and coagulation factor XIII concentrates (Fibrogammin P® 240 U/day for 5 days) were supplemented. Subsequently, the patient was discharged and managed with oral prednisolone and tacrolimus...Coagulation factor XIII deficiency cannot be assessed without measuring coagulation factor XIII activity because common coagulation-fibrinolytic system test results are not abnormal. The measurement of factor XIII activity should be performed when autoimmune diseases are complicated by unexplained bleeding."

Journal • Dermatomyositis • Immunology • Myositis • F13A1

CSL Behring receives FDA approval to expand the indication for Corifact (CSL Behring) - "CSL Behring announced...FDA has approved an expansion of the indication for Corifact... to include the peri-operative management of surgical bleeding in adult and pediatric patients with congenital factor XIII (FXIII) deficiency."

FDA event • Hemophilia

Efficacy and safety of prophylactic treatment with plasma-derived factor XIII concentrate (human) in patients with congenital factor XIII deficiency (Haemophilia) - P3, N=41; NCT00885742; Sponsor: CSL Behring; "The study met its primary endpoint: the upper limit of the 95% CI was substantially below the historical rate of 2.5 bleeding episodes per patient-year. Five spontaneous bleeding episodes (involving three patients; none requiring FXIII treatment) and eight trauma-related bleeding episodes (two requiring FXIII treatment) occurred. Five patients had surgery during the study, only one of whom required FXIII treatment for post-surgical bleeding. Most patients (≥85%) had trough FXIII activity levels ≥10%. No patient discontinued treatment due to an adverse event."

P3 data • Hemophilia

Corifact/Fibrogammin P in the prophylactic treatment of hereditary factor XIII deficiency: Results of a prospective, multicenter, open-label study (Thromb Res) - P3, N=41; NCT00885742; Sponsor: CSL Behring; "...study adds to the wealth of data gained from clinical trials and almost 20 years of clinical use confirming that Corifact™/Fibrogammin® P is an effective and well-tolerated prophylactic treatment for congenital FXIII deficiency."

P3 data • Hemophilia

Current understanding in diagnosis and management of factor XIII deficiency (Iran J Ped Hematol Oncol) - "After diagnosis of disease all patients with severe factor XIII deficiency (<1 U/dl) should receive prophylactic substitution therapy with fresh frozen plasma (FFP) and cryoprecipitate as traditional choices or purified concentrate of blood coagulation factor XIII (Fibrogammin P) inorder to control severe and life-threatening clinical complications of factor XIII deficiency."

Review • Hemophilia

Identification of Potential Novel Interacting Partners for Coagulation Factor XIII B (FXIII-B) Subunit, a Protein Associated with a Rare Bleeding Disorder. (PubMed, Int J Mol Sci) - "In the present study, we have explored the co-presence of protein excipients in commercial FXIII plasma concentrate FibrogamminP by combination of protein purification and mass spectrometry-based verification...The only protein that was observed in both experimental set ups was alpha-2-macroglobulin, which might therefore be a putative interacting partner of the FXIII/FXIII-B subunit. Future functional investigations will be needed to understand the physiological significance of this association."

Journal

A Unique Factor XIII Mutation in Southeastern Iran with an Unexpectedly High Prevalence: Khash Factor XIII. (PubMed, Semin Thromb Hemost) - "...Fibrogammin P has been used worldwide for about one decade, along with different therapeutic regimens for prophylaxis treatment, major and minor surgeries, and successful delivery...The area of Khash city provides novel insights into severe FXIII deficiency due to its high prevalence in this region. This report also provides a review of FXIII deficiency, its diagnosis, prevalence, molecular basis, clinical manifestations, management, and treatment, with a particular focus on Iran, representing a hotspot for this disorder."

Journal • Review