Haemoctin (human plasma derived coagulation factor VIII) / ADMA Biologics - LARVOL DELTA

Low resolution cryo-EM maps and AFM analysis combined with alpha fold model of full-length coagulation Factor VIII sheds light on the conformational positioning of the Factor VIII B domain (#51) (GTH 2023) - "Method The FL-FVIII was purified from two commercial sources of FL-FVIII, one a recombinant (Kovaltry) and the other one a plasma-derived concentrate (Haemoctin) using gel filtration chromatography. Conclusion The FL-FVIII shows a significant amount of conformational variability, most of which is attributed to the disordered B domain. Glycosylation plays a key role in the folding and stabilization of the B domain with respect to the rest of the FL-FVIII."

"El mejor factor es el que llega a tu vena amigo. Acá solo plasmarico de Octanate y de Haemoctin para la Hemofilia A." (@Javierin_A)

Hemophilia

Biotest AG: Biotest increases sales in the first half of 2021 by 10% (Biotest Press Release) - "In the first half of the 2021 financial year, the Biotest Group recorded sales of € 257.8 million (same period in the previous year: € 234.8 million)....In addition, sales of other products such as Haemoctin (R) and Albumin increased compared to the first half of 2020."

Commercial • Genetic Disorders • Hemophilia

RESIST EXP: Rescue Immunotolerance Study in Induction of Immune Tolerance (ITI)-Experienced Patients (RES.I.S.T. Experienced) (clinicaltrials.gov) - P=N/A; N=3; Completed; Sponsor: City of Hope Medical Center; Active, not recruiting ➔ Completed; Trial completion date: Jun 2020 ➔ Oct 2020; Trial primary completion date: Jun 2020 ➔ Oct 2020

Clinical • Trial completion • Trial completion date • Trial primary completion date • Hematological Disorders • Hemophilia • Rare Diseases

RESIST NAIVE: Study of First TIME Immunotolerance Induction in Severe Hemophilia A Patients With Inhibitor at High Risk of Failure: Comparison With FVIII Concentrates With or Without Von Willebrand Factor - RES.I.S.T. Naive (clinicaltrials.gov) - P=N/A; N=0; Withdrawn; Sponsor: City of Hope Medical Center; N=148 ➔ 0; Active, not recruiting ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • Hematological Disorders • Hemophilia • Rare Diseases

Long-Term Safety and Efficacy Data of a Plasma-Derived Factor VIII Concentrate with von Willebrand Factor for Treatment of Patients with Hemophilia A Covering 18 Years. (PubMed, Hamostaseologie) - "We describe the results of the (to our knowledge) longest long-term noninterventional study so far performed to obtain real-life data on the treatment of hemophilia A patients with a single plasma-derived FVIII concentrate containing von Willebrand factor (pdFVIII; Haemoctin/Faktor VIII SDH Intersero)...Inhibitors were found in 13% (3/23) and high-titer inhibitors in 4% (1/23) of previously untreated patients with severe hemophilia A. Four previously treated patients with severe hemophilia A developed inhibitors, thereof three high-titer inhibitors (3.3 and 2.5 high-titer inhibitors in 1,000 patient-years). No unexpected adverse effect on the health of the patients, no pdFVIII-related thrombosis, thromboembolic event, or hypersensitivity reaction, and no suspected viral transmission related to pdFVIII were documented."

Clinical • Journal

VWf containing therapeutic concentrates induce FXII activation, leading to kallikrein activation and bradykinin formation in vitro (GTH 2020) - "Methodology: Three pdFVIII products (Octanate®, Immunate®, Haemoctin®) and four rFVIII products (Kovaltry®, Kogenate®, NovoEight® and Advate®), two pd vWF products (Haemate®, and Wilate®) and rVWf (Vonvendi®) were studied. As the FXII/kallikrein pathway is proinflammatory and as its product bradykinin activates signalling pathways resulting in increased vasodilation, vascular permeability, edema formation and chemotaxis of neutrophils as well as inducing pain, our findings might be of clinical interest. Further research aims to analyse the role of vWF FXII interaction in more detail. Part of the work was supported by a grant of Bayer Vital GmbH, 51368 Leverkusen, Germany"

Preclinical

Biotest AG: Biotest shows excellent efficacy and tolerability of Haemoctin(R) SDH in long-term study of patients with haemophilia A (PharmiWeb) - P=Obs, N=198; "Within this surveillance study, 198 patients representing all age groups (0-88 years) were treated with Haemoctin(R) SDH in Germany and Hungary. 160 patients had severe and 38 non-severe haemophilia A. Data were obtained during prophylactic or on-demand treatment over 18 years (overall 1,418 patient years; mean >7 years treatment time per patient) and analysed....The annual bleeding rate was considerably lower for patients treated prophylactically (median 3.1) than for patients treated only on demand with Haemoctin(R) SDH (median 21.9)."

Observational data

FXII Activation Leading to Kallikrein and Bradykinin Formation in Vitro Induced by Some Plasma Derived FVIII Concentrates, but Not by Recombinant FVIII (ISTH 2019) - " Five pdFVIII products (Octanate®, HaemateP®, Immunate, Haemoctin® and Beriate®) and two rFVIII products (Kovaltry® and Advate®) were studied. As the FXII/kallikrein pathway is proinflammatory and as its product bradykinin activates signaling pathways resulting in increased vasodilation, vascular permeability, edema formation and chemotaxis of neutrophils as well as inducing pain, our findings might be of clinical interest. Further research aims to investigate the effect of factor VIII products ex vivo."

Preclinical

Biotest receives approval for double concentrated Haemoctin SDH for improved haemophilia A treatment in Europe (PharmiWeb) - "Biotest receives approval in 13 European countries for the reduced solvent volume by half for the factor VIII concentrate Haemoctin(R) SDH....Biotest reduced the volume for injection of Haemoctin(R) SDH by half....The approval for the introduction of the reduced volume was already granted for all European countries in which Haemoctin(R) SDH is approved. The national approvals are expected within 2019. Launch in Germany is planned for May 2019."

European regulatory • Launch Europe

Some plasma derived FVIII concentrates activated FXII leading to kallikrein and bradykinin formation in vitro, while recombinant FVIII concentrates did not (GTH 2019) - "Methodology: Five pdFVIII products (Octanate, HaemateP, Immunate, Haemoctin and Beriate ) and two rFVIII products (Kovaltry and Advate) were studied. As the FXII/kallikrein pathway is proinflammatory and as its product bradykinin activates signaling pathways resulting in increased vasodilation, vascular permeability, oedema formation and chemotaxis of neutrophils as well as inducing pain, our findings might be of clinical interest. Further research aims to investigate the effect of factor VIII products ex vivo. This work was supported by a grant of Bayer Vital GmbH, 51368 Leverkusen, Germany"

Preclinical