Bio Products Laboratory Receives European Approval for Coagadex® ▼ (Human Coagulation Factor X)

ELSTREE, England–(BUSINESS WIRE)– Bio Products Laboratory, Limited (BPL) today announced that the European Medicines Agency has granted marketing authorisation for Coagadex. Coagadex is indicated for the treatment and prophylaxis of bleeding episodes and for perioperative management in patients with hereditary factor X deficiency. Coagadex is the first and only treatment licensed specifically for this rare bleeding disorder in Europe.¹

Factor X deficiency is a rare and serious condition caused by not having enough of the Factor X protein in the blood; this protein plays a crucial role in coagulation (blood clotting) which helps patients stop bleeding. People with Factor X deficiency are at increased risk of bleeding or experience excessive or prolonged bleeding. Severely affected individuals, usually children, have an increased risk of bleeding inside the brain, in the lungs or in the gastrointestinal tract, which can be life-threatening.² Hereditary Factor X deficiency is very rare and affects approximately 700 patients in Europe.²

Prof. Flora Peyvandi, Director of Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, Professor of Internal Medicine- IRCCS Maggiore Hospital, University of Milan, commented: “Until now, we have focused on treating Factor X deficiency with blood infusions of plasma or a concentrate of clotting factors. We have wanted a specific Factor X therapy to treat these vulnerable patients. Therefore, the approval of Coagadex in the EU today is a significant advance for patients.”

Dr Steve Austin, Haemophilia Centre Director of St George’s University Hospitals NHS Foundation Trust, London commented: “Having been involved in the clinical development programme of Coagadex, I am delighted that this therapy has now been approved. For the first time, patients with this rare bleeding disorder can receive a specific therapy that has been proven safe and effective in clinical studies.”

Coagadex was approved based upon data generated from two open-label, multicentre, prospective studies.^3,4 The first study enrolled patients with moderate to severe hereditary factor X deficiency who were treated on-demand for spontaneous or traumatic bleeding episodes.³ The primary efficacy endpoints were pharmacokinetic measures including recovery rate and half-life, and secondary endpoints included overall assessment of efficacy and the number of infusions needed to treat a bleed.³

The criteria for treatment success were satisfied in the study, and the pharmacokinetic parameters were consistent with previously published data.³ The overall mean in-vivo recovery rate was 2.0 IU/dL per IU/kg and the half-life was approximately 30 hours.³ There were 187 assessable bleeds in the study with patients rating the treatment as “excellent” in 170 (91%) cases, “good” in 14 (7.5%) cases, and “poor” in 2 (1.1%) cases.³ In addition, most bleeding episodes (155/187 [82.9%]) were effectively treated with only one infusion of Coagadex.³

Two patients in the study reported six adverse events considered possibly related to the medication: two events of fatigue in one patient, two events of infusion site erythema in one patient, and one of infusion site pain and back pain in each patient.³ There were no other drug-related adverse events, no serious drug-related adverse events, and no patients discontinued from the study due to adverse events.³

The second study collected data on two surgical patients receiving Coagadex perioperatively.⁴ Surgical data from three patients in the first study was added and resulted in five patients undergoing seven surgical procedures.⁴ For all surgical procedures, Coagadex was assessed by the investigator as excellent in controlling blood loss during and after surgery.⁴ All patients undergoing major surgery were diagnosed with mild factor X deficiency (i.e., factor X level >5 IU/dL and < 20 IU/dL).⁴ One patient with moderate deficiency and two with severe deficiency underwent minor procedures.⁴ No patients with moderate or severe disease underwent a major procedure.⁴ There were no treatment-related adverse events reported in surgical patients in the second study.⁴

In both studies combined, the most common adverse events were infusion site erythema, infusion site pain, fatigue and back pain.^3,4

John Perkins, CEO of BPL, commented: “BPL has over 60 years of expertise in plasma product manufacturing and we are proud of our achievements to date. Coagadex is a first of its kind medicine for this rare coagulation disorder. This achievement is a demonstration of our commitment to patients in areas with the greatest unmet need.”

ENDS

About Bio Products Laboratory Limited

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 exports to 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.

Notes to editors

About Coagadex

Coagadex is derived from human plasma and used as a replacement for the naturally existing coagulation Factor X in patients with hereditary Factor X deficiency. In the EU, Coagadex is indicated for the treatment and prophylaxis of bleeding episodes and for perioperative management in patients with hereditary factor X deficiency. It was first approved by the Food and Drug Administration (FDA) in October 2015. A paediatric trial of Coagadex is ongoing.

Abbreviated Prescribing Information

Please refer to the Summary of Product Characteristics (SmPC) before prescribing.

Presentation:

Powder and solvent for solution for injection, nominally 250 IU and 500 IU presentations. Approximately 100 IU/mL human coagulation factor X after reconstitution with 2.5 mL (250 IU) or 5 mL (500 IU) sterilised water for injections.

Therapeutic indications:

Treatment and prophylaxis of bleeding episodes and for perioperative management in patients with hereditary factor X deficiency.

Posology and method of administration:

For intravenous use only.

Required dose (IU) = body weight (kg) x desired factor X rise (IU/dL or % of normal) x 0.5.

Treatment of bleeding episodes: 25 IU/kg when bleeding occurs or just before expected onset of menstrual bleeding. Repeat every 24 hours until the bleed stops.

Prophylaxis: 25 IU/kg prior to anticipated physical activity, dental appointments and secondary prophylaxis against re-bleeding. Repeat as required. Limited data are available for longer prophylaxis periods but 24.6 to 28 IU/kg once weekly or 25 IU every two weeks have been used.

Perioperative Management: Pre-surgery: raise plasma factor X levels to 70-90 IU/dL. The careful treatment dose and duration control is recommended in major surgery. Post-surgery: maintain plasma factor X levels at a minimum of 50 IU/dL until the subject is no longer at risk of bleeding due to surgery. Plasma factor X levels post-infusion should be monitored before and after surgery to ensure that haemostatic levels are obtained and maintained; mean half-life is 30.3 hours.

Administration: after reconstitution infuse intravenously at a suggested rate of 10 mL/minute but no more than 20 mL/minute.

Contraindications:

Hypersensitivity to the active substance or any of the excipients.

Special warnings and precautions:

Hypersensitivity reactions have been observed rarely in other haemophilias and are possible; early signs include angioedema, infusion site inflammation, chills, cough, dizziness, fever, flushing, generalised urticaria, headache, hives, hypotension, lethargy, musculoskeletal pains, nausea, pruritus, rash, restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing. When products prepared from human plasma are administered, the risk of transmission of infective agents, known or unknown, cannot be totally excluded. Patients with factor X deficiency may develop neutralising antibodies (inhibitors) to factor X. Monitor patients for inhibitor development by clinical observation and laboratory tests. No more than 60 IU/kg daily should be administered. Coagadex contains up to 0.4 mmol/mL (9.2 mg/mL) of sodium, which should be taken into consideration for patients on a controlled sodium diet.

Undesirable effects:

Common: back pain, infusion site erythema, infusion site pain, fatigue. Unknown frequency: no post marketing data available.

Overdose:

One case of accidental overdose was reported in the clinical trials, in which a subject received approximately 80 IU/kg Coagadex to treat a bleed. No adverse events were reported relating to this overdose. There is a potential for thromboembolism with overdose.

Pharmaceutical precautions: Shelf life at max. 30^oC: 3 years. Do not freeze.

Category: POM

Packaging quantities: Nominal 250 IU and 500 IU vials.

Marketing authorisation number and holder: 250 IU EU/1/16/1087/001, 500 IU EU/1/16/1087/002. BPL, Bio Products Laboratory Limited, Dagger Lane, Elstree, Herts, WD6 3BX. U.K.

Date of preparation: March 2016

Adverse events should be reported.
Reporting forms and information can be found at www.mhra.gov.uk/yellowcard
Adverse events should also be reported to BPL Medical Department on 020 8957 2255 or
adr@bpl.co.uk

▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

References

¹ Coagadex (Human Coagulation Factor X) Summary of Product Characteristics. 2016

² PK Gupta, Col H Kumar, S Kumar. Hereditary Factor X (Stuart-Prower Factor) Deficiency. MJAFI, Vol. 64, No. 3, 2008. http://medind.nic.in/maa/t08/i3/maat08i3p286.pdf [Last accessed January 2016]

³ BPL-TEN01-0414, NCT00930176

⁴ BPL-TEN03-0514, NCT01086852

UK/CF/0316/0003 – March 2016