FDA Approvals Strengthen Octapharma USA Pediatric Critical Care Product Portfolio
Octaplas™ and fibryga® receive new product labeling following FDA’s approval of BLA supplements to update therapy research
FDA expands fibryga® indication to include treatment of acute bleeding episodes in pediatric congenital fibrinogen deficiency patients under 12 years of age
PARAMUS, N.J. (March 29, 2021) – The U.S. Food and Drug Administration (FDA) has approved two Octapharma supplements to Biological License Applications, strengthening the company’s pediatric critical care product portfolio. The supplement approvals resulted in new product labeling for Octaplas™, Pooled Plasma (Human), Solvent/Detergent (S/D) Treated Solution for Intravenous Infusion, and fibryga®, Fibrinogen (Human) Lyophilized Powder for Reconstitution.
The Octaplas™ labeling now provides the results of two post-marketing studies (LAS-212, LAS-213) evaluating the product’s efficacy, safety and tolerability for newborns through age 20. Octaplas™, an alternative to fresh frozen plasma, was evaluated in 91 pediatric patients up to age 20. There were no hyperfibrinolytic or treatment-related thromboembolic events reported by investigators. Results of these studies support the use of Octaplas™ in critically ill pediatric patients.
“These two studies with Octaplas™ are an important addition to the pediatric literature and provide supportive data for a virus-inactivated plasma option in these patients,” said Cassandra Josephson, MD, Professor of Pathology and Laboratory Medicine and Pediatrics at Emory University School of Medicine in Atlanta, Ga.
The new Octaplas™ prescribing information adds data from the LAS-213 clinical trial to assess the safety and tolerability of the product in the pediatric population (ClinicalTrials.gov: LAS 213, NCT01938378). The prospective, open-label, multicenter, single-arm post-marketing study evaluated Octaplas™ in the management of patients who underwent therapeutic plasma exchange (TPE). Patients were dosed based on body weight and doses were adjusted as needed.
A total of 102 TPE procedures were performed in 41 patients aged 2 to 20 years (15 between ages 2 and 12; 13 between ages 12 and 17; and 13 between the ages of 17 and 20). Fourteen participants had immune system disorders; 12 had nervous system disorders; 8 had renal and urinary disorders; 4 had infections and infestations; and 3 had other disorders. No thrombotic or thromboembolic events were found in any study participant. In total, 8 adverse reactions were found in 4 patients. Most adverse reactions (7 of 8) were mild in intensity and were recovered/resolved by the end of the study. No treatment-related serious adverse events were reported. Overall safety was assessed by investigators as excellent for most subjects (>90%) at 24 hours after each TPE throughout the study using prespecified definitions of excellent, good and poor.
An earlier study (LAS-212) published in the Frontiers in Pediatrics, supported the use of Octaplas™ in the management of pediatric patients who require replacement of multiple plasma coagulation factors. The prospective, open-label, multicenter, single arm, post-marketing study (ClinicalTrials.gov: LAS-212 NCT02050841) assessed 50 pediatric patients age 16 years and under (37 neonates/infants, less than age 2; and 13 children/adolescents, age 2 to 16). Study participants included 40 cardiac surgery patients, 5 liver transplant/dysfunction patients, 4 sepsis-related coagulopathy patients and 1 patient with hypoxic encephalopathy. Overall safety was assessed by investigators as excellent for all 50 patients.
“We are very pleased to announce the supplemental approvals for both Octaplas™ and fibryga®,” said Octapharma USA President Flemming Nielsen. “Critical care medicine is an important part of Octapharma’s therapeutic focus and we are committed to working with researchers to advance patient treatment options. Providing the resources and expertise to better manage rare disease continues to be one of our main goals.”
For fibryga®, human fibrinogen concentrate, the FDA approved Octapharma’s request to expand the indication for on-demand treatment of acute bleeding episodes to pediatric patients less than 12 years old with congenital fibrinogen deficiency (CFD), also known as Factor 1 deficiency. The expansion was supported by the results of a Phase 3 study recently published in Haemophilia. Researchers observed the efficacy, pharmacokinetics and safety of treatment with fibryga® in 14 pediatric patients with CFD.
A recent case report in the Journal of Thrombosis and Haemostasis reported on the treatment of a pediatric congenital afibrinogenemia patient. The patient received fibryga® for long-term prophylaxis after experiencing allergic reactions to other replacement therapies, and for perioperative management during liver transplantation. “Our case report provides further evidence for the safety and tolerability of this human fibrinogen concentrate in a pediatric patient with CFD,” said Fernando F. Corrales-Medina, MD of the University of Miami-Hemophilia Treatment Center.
Additionally, earlier research published in the Journal of Thrombosis and Haemostasis reported on the use of fibryga® for on‐demand treatment of bleeding and surgical prophylaxis in 25 adult and adolescent patients with afibrinogenemia. Fibryga® is not approved for use as prophylactic treatment.
Three research posters on fibryga® will be presented at the virtual American Society of Pediatric Hematology/Oncology (ASPHO) 2021 conference to be held April 20 – 23. The poster titles are:
Human Fibrinogen Concentrate for Bleeding Prophylaxis During Surgery in Adult, Adolescent and Pediatric Patients with Congenital Fibrinogen Deficiency: Results from the FORMA-02 and FORMA-04 Clinical Trials
Analysis of Fibrinogen Concentrate Pharmacokinetics and Dosing in Adult, Adolescent and Pediatric Patients with Congenital Fibrinogen Deficiency
Efficacy and Safety of Human Fibrinogen Concentrate in Pediatric and Adolescent Patients with Congenital Fibrinogen Deficiency: Results from the FORMA-02 and FORMA-04 Clinical Trials
For ASPHO program information, please visit ASPHO.org.
Fibryga®, Fibrinogen (Human) Lyophilized Powder for Reconstitution, for Intravenous Use, is a human fibrinogen concentrate indicated for the treatment of acute bleeding episodes in adults and children with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia. Fibryga® is not indicated for dysfibrinogenemia. Fibryga® is stored as a lyophilized powder at room temperature or refrigerated temperature [+2°C to + 25°C (36°F to 77°F)] for up to 30 months from the date of manufacture. The product can be reconstituted with sterile water within approximately 5 to 10 minutes with the provided Octajet transfer device and particle filter (17-micron).
Fibryga® is contraindicated in individuals who have manifested severe immediate hypersensitivity reactions, including anaphylaxis, to fibryga® or its components.
WARNINGS AND PRECAUTIONS
Monitor patients for early signs of hypersensitivity or allergic reactions. If necessary, discontinue administration and institute appropriate treatment.
Thrombotic events have been reported in patients receiving fibryga®. Treatment with human fibrinogen concentrate has been associated with thrombosis at target plasma fibrinogen levels that were below 150 mg/dL. The thrombotic risks may be greater when the target fibrinogen plasma level is 150 mg/dL. Weigh the benefits of administration versus the risks of thrombosis.
Fibryga® is made from pooled human plasma. Products made from human plasma may contain infectious agents, e.g., viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.
The fibryga® manufacturing process includes a solvent/detergent (S/D) step for virus inactivation, and a nanofiltration step (Planova 20N nanofilter or Pegasus SV4 nanofilter) for virus removal. For complete prescribing information, please visit fibrygausa.com.
Octaplas™ is a solvent/detergent (S/D) treated, pooled human plasma indicated for replacement of multiple coagulation factors in patients with acquired deficiencies due to liver disease or who are undergoing cardiac surgery or liver transplantation; and plasma exchange in patients with thrombotic thrombocytopenic purpura (TTP).
Octaplas™ is contraindicated in patients with immunoglobulin A (IgA) deficiency; severe deficiency of protein S; history of hypersensitivity to fresh frozen plasma or to plasma-derived products including any plasma protein; or a history of hypersensitivity reaction to Octaplas™.
WARNINGS AND PRECAUTIONS
Transfusion reactions can occur with ABO blood group mismatches; high infusion rates can induce hypervolemia with consequent pulmonary edema or heart failure; excessive bleeding due to hyperfibrinolysis can occur due to low levels of alpha 2-antiplasmin; thrombosis can occur due to low levels of Protein S; citrate toxicity can occur with volumes exceeding one milliliter of Octaplas™ per kg per minute; Octaplas™ is made from human blood and may carry the risk of transmitting infectious agents, e.g., viruses and theoretically, the variant Creutzfeldt-Jakob disease and Creutzfeldt-Jakob disease agent.
For complete prescribing information, please visit octaplasus.com.
About the Octapharma Group
Headquartered in Lachen, Switzerland, Octapharma is one of the largest human protein manufacturers in the world, developing and producing human proteins from human plasma and human cell lines.
Octapharma employs more than 9,000 people worldwide to support the treatment of patients in 118 countries with products across three therapeutic areas: Hematology, Immunotherapy and Critical Care.
Octapharma has seven research and development sites and six state-of-the-art manufacturing facilities in Austria, France, Germany, Mexico and Sweden, and operates more than 160 plasma donation centers across Europe and the U.S. Octapharma USA is located in Paramus, N.J. For more information, please visit www.octapharmausa.com.