Octanate (human Factor VIII/von Willebrand Factor) / Octapharma - LARVOL DELTA

Longitudinal Patient Analysis Suggests a Positive Correlation of IL-10/IL-6 and FVIII Inhibitor Amount (ASH 2023) - "Prophylactic treatment began at the age of 9 months with 30IU/kg Octanate, and after four days of exposure, the formation of inhibitors was initially detected...Preliminary data suggest a positive correlation between both cytokines and active inhibitor presence. However, to reach a definitive conclusion, the sample size will be/should be increased."

Clinical • Diabetes • Hematological Disorders • Hemophilia • Hepatitis C • Infectious Disease • Metabolic Disorders • Rare Diseases • Type 1 Diabetes Mellitus • CXCL8 • IFNG • IL10 • IL17A • IL18 • IL1B • IL23A • IL33 • IL6 • TNFA

Protect-NOW: Efficacy, Safety & Utilisation of Nuwiq, Octanate and Wilate in Previously Untreated & Minimally Treated Haemophilia A Patients (clinicaltrials.gov) - P=N/A | N=200 | Recruiting | Sponsor: Octapharma | N=140 ➔ 200

Enrollment change • Hematological Disorders • Hemophilia • Rare Diseases

Design of a Real-World Observational Study in Previously Untreated and Minimally Treated Hemophilia A Patients: Protect-NOW. (PubMed, TH Open) - P=N/A | "Background  The efficacy, safety, and immunogenicity of each of Octapharma's factor VIII (FVIII) products, Nuwiq, octanate, and wilate, have been investigated in previously untreated patients (PUPs) with severe hemophilia A in prospective clinical trials. The secondary objectives are to assess utilization patterns (including dosage and frequency of administration) and the effectiveness in surgical prophylaxis. Conclusions  The Protect-NOW study will provide information on the treatment of PUPs and MTPs in routine clinical practice, which will help guide clinical decision making for treating these patients in the future."

Journal • Observational data • Real-world • Real-world evidence • Hematological Disorders • Hemophilia • Rare Diseases

Immunogenicity of Two Plasma-Derived FVIII Products and Simoctocog Alfa in Previously Untreated Patients According to F8 Mutation Type (ASH 2018) - "Conclusion s: PUPs with non-null F8 mutations did not develop inhibitors when treated with octanate®, wilate® or Nuwiq®. Whilst the different studies are not directly comparable, the findings with these products, two pdFVIII/VWF and a rFVIII from a human cell line, show similar behavior to the SIPPET trial where no patients with non-null mutations treated with pdFVIII/VWF products developed inhibitors."

Clinical • Biosimilar • Gene Therapies • Hematological Disorders • Hemophilia

ANALYSIS OF FACTOR VIII LEVELS IN HAEMOPHILIA A TREATED PATIENTS - PRELIMINARY RESULTS OF PHARMACOKINETIC STUDY (EAHAD 2023) - "This retrospective study aimed to analyse factor VIII (FVIII) levels, as effectiveness of prophylaxis, in severe haemophilia A patients treated in two Estonian Haemophilia Treatment Centres. From January 2019 to April 2021, in total 28 PK-profiles in 21 subjects (10 adults and 11 children) were analysed: Nuwiq (n= 6), Octanate (n= 2), Adynovi (n= 8), Elocta (n=12). Our study results demonstrated that in EHL treated patients FVIII levels are higher at particular time points when comparing to SHL-products. In future perspective, implementing available tools like WAPPS-Hemo (Web Accessible Population Pharmacokinetics Service – Haemophilia, McMaster University, Canada) with additional PK parameters would be evaluated for optimized individualized therapeutic approach."

Clinical • PK/PD data • Hematological Disorders • Hemophilia • Obesity • Rare Diseases

A snapshot analysis of a prospective, non-interventional study to evaluate real-life prophylactic treatment schedules of factor VIII concentrates (#153) (GTH 2023) - "It further aims to analyze all aspects of prophylactic treatment with Simoctocog alfa (Nuwiq) and the plasma-derived FVIII concentrates Wilate and Octanate. No inhibitor formation or any other adverse drug reactions were observed. Conclusion This snapshot analysis with a long observation time of a median of 31.5 months delivered important data on the ABR in real-life treatment of haemophilia A. It further confirms the outstanding tolerability and efficacy of the concentrates investigated."

Clinical • Observational data • Hematological Disorders • Hemophilia • Rare Diseases

Practical utilisation of Octapharma FVIII concentrates in previously untreated and minimally treated haemophilia A patients entering routine clinical treatment – The Protect-NOW Study (ISTH 2022) - P=N/A | "The incidence of high-titre inhibitors was 16%, 8% and 11% in trials with Nuwiq®, octanate® and wilate®, respectively...Patients on concomitant emicizumab prophylaxis may be included in the study... As of January 2022, 51 patients have been enrolled in the study from 29 sites in 14 countries. Recruitment is ongoing, and additional sites are being initiated. Conclusion(s): Protect-NOW is collecting real-world data on the effectiveness and safety of Octapharma FVIII products in routine clinical practice in PUPs and MTPs."

Clinical • Hematological Disorders • Hemophilia • Rare Diseases

Dose optimisation in children with severe haemophilia A on long-term octanate® prophylaxis (ISTH 2022) - "Four groups were defined based on the dosing interval and the presence or absence of bleeding episodes (BEs; spontaneous or associated with increased physical activity) in the previous year (Table 1). The estimated time to 1% FVIII activity for children on a 72-h dosing interval was 78 h in those with no previous BEs (Group 1) and 70 h in those with previous BEs (Group 2). For patients on a 96-h dosing interval, the values were 116 h in children without previous BEs (Group 3) and 111 h in those with previous BEs (Group 4)."

Clinical • Hematological Disorders • Hemophilia • Rare Diseases

Protect-NOW: Efficacy, Safety & Utilisation of Nuwiq, Octanate and Wilate in Previously Untreated & Minimally Treated Haemophilia A Patients (clinicaltrials.gov) - P=N/A | N=140 | Recruiting | Sponsor: Octapharma | Trial completion date: Jun 2023 ➔ Jun 2030 | Trial primary completion date: Jun 2023 ➔ Jun 2030

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

Immune Tolerance Induction (ITI) with a pdFVIII/VWF Concentrate (octanate) in 100 Patients in the Observational ITI (ObsITI) Study. (PubMed, TH Open) - "PS and CS were achieved in a median of 5.55 and 11.25 months, respectively. Conclusions  ITI with pdFVIII/VWF led to rapid eradication of FVIII inhibitors, normalization of FVIII pharmacokinetics in the majority of patients, and a significant reduction in bleeding rates."

Journal • Hematological Disorders • Hemophilia • Rare Diseases

"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

A patient with FVIII inhibitors on emicizumab prophylaxis switching to immune tolerance induction laboratory issues (BIC 2021) - "One month after the last dose, the boy was switched to ITI with daily administration of plasma-derived FVIII concentrate (Octanate 2500 IU/L). Residual emicizumab activity after discontinuation needs to be taken into consideration when performing clot-based coagulation assays in further follow-up of patients. Regarding inhibitor testing, unlike clotting assay, both chromogenic methods enabled reliable quantification."

Clinical • Hematological Disorders • Hemophilia • Rare Diseases

Design of an international investigator-initiated study on MOdern Treatment of Inhibitor-positiVe pATiEnts with haemophilia A (MOTIVATE). (PubMed, Ther Adv Hematol) - P=N/A, P4 | "The following treatment approaches will be evaluated: Group 1 - ITI with Nuwiq, octanate or wilate and aPCC/rFVIIa if needed to treat bleeding episodes (BEs) or during surgery or for prophylaxis; Group 2 - ITI with Nuwiq, octanate or wilate and emicizumab prophylaxis and aPCC/rFVIIa if needed to treat BEs or during surgery; Group 3 - routine prophylaxis with emicizumab, aPCC or rFVIIa without ITI and aPCC/rFVIIa if needed to treat BEs or during surgery. It is planned to enrol 120 patients who will be followed for up to 5 years. Optional sub-studies will explore factors that may influence ITI results as well as the impact of different treatment approaches on important aspects of patient health, including joint and bone health and the risk of thrombotic events."

Clinical • Journal • Hematological Disorders • Hemophilia • Rare Diseases

[VIRTUAL] PRactical Utilisation of Octapharma FVIII Concentrates in Previously Untreated and Minimally Treated Haemophilia A Patients Entering Routine Clinical Treatment with Nuwiq®, octanate® or wilate® – The Protect-NOW Study (ISTH 2021) - "Results : As of March 2021, 37 patients have been enrolled in the study from 13 sites in Belarus, Canada, France, Germany, Italy, Lithuania, Spain and the United Kingdom, with additional sites to be initiated. Conclusions : Protect-NOW is collecting clinically relevant information on the outcomes of PUPs and MTPs treated with Octapharma‘s FVIII products in a real-world setting."

Clinical • Hematological Disorders • Hemophilia • Rare Diseases

Octapharma's ongoing dedication to improving the lives of people with haemophilia and von Willebrand disease to be showcased at the ISTH 2021 Congress (PRNewswire) - "Octapharma announced today that new clinical and scientific findings encompassing their Haematology portfolio, including Nuwiq®, wilate®, octanate® and octanine®F, will be presented at the upcoming International Society on Thrombosis and Haemostasis (ISTH) Virtual Congress, taking place on July 17–21, 2021."

Clinical data • Hemophilia

Personalised Prophylaxis in a Child with Haemophilia A and Type 1 Diabetes. (PubMed, Clin Pract) - "After six years, the haemophilia treatment was changed from a plasma-derived factor VIII (FVIII) concentrate (octanate, Octapharma, Lachen, Switzerland) to Nuwiq (simocotocog alfa, Octapharma, Lachen, Switzerland), a recombinant FVIII (rFVIII) product from a human cell line, which allowed for a personalised treatment schedule that supported good adherence. rFVIII was well tolerated, with no treatment-related adverse events observed. This case illustrates the importance of treatment personalisation for young patients and their families managing concomitant diseases."

Clinical • Journal • Review • Diabetes • Hematological Disorders • Hemophilia • Metabolic Disorders • Rare Diseases • Type 1 Diabetes Mellitus

MOTIVATE (MOdern Treatment of Inhibitor-positiVe pATiEnts with haemophilia A) enrolls first patient in the US (PRNewswire) - P=Obs, N=120; NCT04023019; "Dr Robert Sidonio and Dr Carmen Escuriola-Ettingshausen have announced that MOTIVATE (MOdern Treatment of Inhibitor-positiVe pATiEnts with haemophilia A) has commenced patient enrollment in the US....MOTIVATE provides an exciting opportunity to collect real-world clinical data on modern approaches to treating patients with hemophilia A and inhibitors, and to compare the efficacy and safety of different treatment approaches. The study is investigating ITI with and without emicizumab prophylaxis....Dr Escuriola-Ettingshausen...explained 'Real-world data from MOTIVATE and its sub-studies will help us greatly to understand how to optimize treatment for hemophilia A patients with inhibitors to improve patient outcomes'."

Media quote • Observational data • Hemophilia

Evaluation of the digestion and transport profiles and potential immunocompetence of puerarin and its acylated derivatives. (PubMed, Food Funct) - "The apparent permeability coefficients of puerarin, puerarin acetate, puerarin propanoate, puerarin butyrate, puerarin hexanoate, puerarin octanate and puerarin laurate were 1.62 ± 0.09, 1.70 ± 0.15, 1.89 ± 0.19, 1.86 ± 0.18, 2.29 ± 0.12, 4.06 ± 1.01 and 2.32 ± 0.88 × 10-6 cm s-1, respectively, in Caco-2 cell monolayers...These findings suggested that a better absorption could be predicted after oral intake using PAES. Meanwhile, the concentration of esters and their metabolites (puerarin) found in the digestion and transport profiles directly affected their potential immunocompetence."

Journal • IL10 • IL6 • TNFA

[VIRTUAL] PHARMACOKINETIC DIFFERENCES IN HEMOPHILIA A BASED ON FVIII PRODUCT AND ON ASSAY TYPE (EAHAD 2021) - "Regarding SHL products, there were 30 PK evaluations with t1/2 (OSA) vs. t1/2 (CSA) for “Advate” (8): 10.2 hours vs. 8.4 h; for “Kogenate” (11): 11.9 hours vs. 11.1 h; for “Kovaltry” (3): 16.6 hours vs. 13.9 h; for “Octanate” (8): 17.1 hours vs. 15.2 hours. About EHL products, there were 15 PK assays with t1/2 (OSA) vs. t1/2 (CSA) for “Elocta” (13): 14.4 hours vs. 16.8 h; for “Adynovi” (2): 24.4 hours vs. 22.6 hours... In all products but “Elocta”, t1/2 evaluated with OSA were higher than t1/2 evaluated with CSA. It is still uncertain whether “Elocta” correlates with higher FVIII levels on CSA and if this fact was relevant for our statistically significant results in t1/2 of EHL in CSA. Interestingly, plasma-derived product presented higher t1/2 than recombinant products, even though n.s. Although the number of studied patients was low to draft definitive conclusions, making comparison analysis between products..."

PK/PD data • Hematological Disorders • Hemophilia • Rare Diseases

Protect-NOW: Efficacy, Safety & Utilisation of Nuwiq, Octanate and Wilate in Previously Untreated & Minimally Treated Haemophilia A Patients (clinicaltrials.gov) - P=N/A; N=140; Recruiting; Sponsor: Octapharma; Trial completion date: Jun 2022 ➔ Jun 2023; Trial primary completion date: Jun 2022 ➔ Jun 2023

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

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

Immune tolerance induction (ITI) with a single factor VIII/von willebrand factor concentrate in haemophilia A patients with inhibitors – Data from the obsiti study (EAHAD 2020) - P=N/A; "ITI with octanate® was successful in a large proportion of patients and led to rapid, sustained eradication of FVIII inhibitors."

Clinical • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

MOTIVATE (MOdern Treatment of Inhibitor-positiVe pATiEnts with haemophilia A) Begins Patient Recruitment (Canada Newswire) - "Dr Carmen Escuriola-Ettingshausen and Dr Robert Sidonio are pleased to announce that MOTIVATE (MOdern Treatment of Inhibitor-positiVe pATiEnts with haemophilia A) has been approved in the United States and Europe and is now recruiting participants....Three patient groups will be evaluated based on their treatment approach: ITI (with the human cell line-derived recombinant FVIII Nuwiq® or the plasma-derived FVIII products octanate® or wilate®); ITI (with Nuwiq®, octanate® or wilate®) and emicizumab prophylaxis; Routine prophylaxis with emicizumab, aPCC or rFVIIa without ITI....MOTIVATE aims to enrol a total of 120 patients of any age and with haemophilia A of any severity who have developed inhibitors to any FVIII product."

Trial status • Hemophilia

[VIRTUAL] Immune Tolerance Induction with Octanate® in Patients with Haemophilia A and Inhibitors: An Ongoing Case Series from a Malaysian Centre (ISTH 2020) - "These data indicate a high success rate and rapid achievement of negative inhibitor titres with octanate® in patients with severe haemophilia A and inhibitors. Moderate dose regimens for ITI can successfully eradicate inhibitors and make ITI feasible in countries with limited resources."

Clinical • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases