– Supplemental BLA based on clinical trial results from the Phase 3 TEN02 Study, a prospective study of Coagadex® for prophylaxis of bleeding episodes in children under 12 years old with moderate to severe hereditary factor X deficiency

– FDA previously granted Coagadex® Orphan Drug Designation for the treatment of hereditary factor X deficiency

ELSTREE, UK and DURHAM, NC, USA I May 23, 2018 I Bio Products Laboratory Limited (BPL), a leading manufacturer of plasma-derived protein therapies, announced today that the U.S. Food and Drug Administration (FDA) has accepted for filing a supplemental Biologics License Application (BLA) for Coagadex® (Coagulation Factor X, Human) for prophylactic treatment of hereditary factor X deficiency, as well as treatment in children under 12 years of age.

“BPL is dedicated to improving the lives of patients with bleeding and clotting disorders, and is extremely pleased that FDA has accepted our supplemental BLA with Priority Review,” said Eric Wolford, PharmD, Vice President of Global Medical at BPL. “The addition of prophylactic and pediatric data to the prescribing information would represent another key step to ensure patients receive appropriate treatment for hereditary factor X deficiency, a rare and serious condition.”

The submission of the supplemental BLA is based on data from TEN02, the Phase 3 prospective study of Coagadex® (Coagulation Factor X, Human) for prophylaxis of bleeding episodes in children under 12 years old with moderate to severe hereditary factor X deficiency. Coagadex was first approved in October 2015 for the treatment of adults and children (aged 12 years and over) with hereditary factor X deficiency for on-demand treatment and control of bleeding episodes, and perioperative management of bleeding in patients with mild hereditary factor X deficiency. Coagadex is the first and only FDA-approved product to treat hereditary factor X deficiency and is the only specific factor X concentrate available in the U.S.

In granting Priority Review for the application, the FDA’s goal is to review and take action within six months instead of the typical 10-month timeline.  Priority Review designation is granted to applications for drugs that, if approved, would provide significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications. 

About TEN02

TEN02 (ClinicalTrials.gov NCT01721681) was an open-label, multicenter, non-randomized, phase 3, prospective study conducted in subjects <12 years of age with a diagnosis of moderate or severe hereditary factor X deficiency (basal plasma factor X activity <5 IU/dL at diagnosis) and either a history of severe bleeding or an F10 gene mutation causing a documented severe bleeding type.

The primary endpoint of the study was the investigator’s assessment of overall efficacy of Coagadex®, which was rated as “excellent” by the investigators for all subjects in the per-protocol population. A prophylactic dosing regimen of 40–50 IU/kg twice weekly was recommended in the study; dose and frequency were adjusted over the initial six weeks to maintain factor X concentration levels ≥5 IU/dL (with peak levels ≤120 IU/dL). On-demand use was also assessed, where appropriate. For acute bleeds, on-demand treatment was to be initiated at 25 IU/kg, consistent with on-demand dosing in the approved population of patients over 12 years of age. The data from this study demonstrates Coagadex to be efficacious when administered as routine prophylaxis to subjects aged <12 years with hereditary FX deficiency, and for on-demand treatment of bleeds. In addition, the safety analysis demonstrates that Coagadex is well-tolerated in this population.

A total of 28 treatment-emergent adverse events (TEAEs) were reported in 8 unique subjects, (88.9%) of the treated population, none of which was considered related to treatment. The majority of TEAEs (n=26; 92.9%) were mild in severity; the remaining 2 TEAEs (7.1%) were of moderate severity. The most common TEAEs were pyrexia and nasopharyngitis, both with 4 events in 3 unique subjects.  Two serious adverse events (mild influenza, and moderate lower respiratory tract infection) were reported in one subject; neither was considered treatment related by the investigator.  No deaths or other serious AEs were reported.

Additional information on the TEN02 clinical trial and its results can be found by visiting https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.13500.

About Factor X Deficiency

Hereditary factor X deficiency is a rare bleeding disorder that affects approximately 300-600 patients in the U.S.  Affected individuals often have inadequate amounts of circulating factor X, an important component of the coagulation system. Factor X deficient patients are at increased risk of bleeding and need to be managed similarly to hemophilia patients.

Please see the Important Safety Information below and www.coagadex.com for full prescribing information.

Indications for Coagadex

Coagadex, a plasma-derived blood coagulation factor X concentrate, is indicated in adults and children (aged 12 years and above) with hereditary Factor X deficiency for:

  • On-demand treatment and control of bleeding episodes
  • Perioperative management of bleeding in patients with mild hereditary Factor X deficiency

Limitation of Use

Perioperative management of bleeding in major surgery in patients with moderate and severe hereditary Factor X deficiency has not been studied.

Important Safety Information for Coagadex

Coagadex is contraindicated in patients with known hypersensitivity to any of the components of the product.

Allergic type hypersensitivity reactions, including anaphylaxis, are possible with Coagadex. If symptoms occur, patients should discontinue use of the product immediately and contact their physician.

The formation of neutralizing antibodies (inhibitors) to factor X is a possible complication in the management of individuals with factor X deficiency. Carefully monitor patients taking Coagadex for the development of inhibitors by appropriate clinical observations and laboratory tests.

Coagadex is made from human plasma and may contain infectious agents, e.g. viruses and, theoretically, the Creutzfeldt-Jakob disease agent. No cases of transmission of viral diseases, vCJD or CJD, have been associated with the use of Coagadex.

In clinical studies, the most common adverse reactions (frequency ≥5% of subjects) with Coagadex were infusion site erythema, infusion site pain, fatigue and back pain.

For complete Prescribing Information for Coagadex please see www.coagadex.com.

About Bio Products Laboratory, Ltd.

Bio Products laboratory, Limited (BPL) is a leading manufacturer of plasma-derived protein therapies with global headquarters in Elstree, England, US headquarters in Durham, NC, and a presence in more than 45 countries worldwide.  The company has over 60 years of experience developing and manufacturing plasma-derived therapies since being established as part of the Lister Institute in 1950, and currently markets a wide range of products, including coagulation factors, human immunoglobulins, and albumin.  BPL is committed to continued investment in research and development to maintain its key position as a reliable supplier of high-quality products to patients and healthcare providers worldwide.

SOURCE: Bio Products Laboratories