2016年6月12日，Coagadex获欧美批准上市，这是首个获批的治疗罕见出血性疾病——遗传性凝血因子X缺陷症的药物。
与血友病相似，凝血因子X缺陷是一种遗传性疾病，男性和女性的患病率相同，患者主要症状是出血不止。据估计，该疾病的患病率是1/500，000，欧洲的患者数量大约是700人，患者有可能出现脑部、肺部、胃肠道的出血，有可能造成生命危险。
Coagadex是一种血浆来源的凝血因子X，去年10月份，FDA批准其用于控制12岁以上患者的出血症状，以及具有轻度出血症状的患者在手术中使用。今年3月份，该药物在欧洲获批，用于出血时间的治疗和预防，以及围手术期患者出血情况控制。FDA批准该药物是基于一项开放性临床试验的数据，受试者为16名患有中度至重度遗传性凝血因子X缺陷的患者，结果表明患者仅需服用一剂药物就能够有效地控制出血症状，并且恢复的速度也很快。
COAGADEX(凝血因子X(人)Coagulation Factor X, Human)为静脉注射溶液/冻干燥粉
初次批准：[2015]
作用机制
COAGADEX暂时地取代丢失的对有效止血需要的因子X。因子X是一种无活性的酶原，它可被因子IXa (通过内在通路)或被因子VIIa(通过外在通路)激活。因子X从其无活性形式转换为活性形式(因子Xa)通过一个52-残基肽从重链的裂解。因子Xa与因子Va在一个磷脂表面上结合形成凝血酶原酶复合物，它在存在钙离子时激活凝血酶原为凝血酶。然后凝血酶作用与可溶性纤维蛋白和因子XIII形成一个交联纤维蛋白凝块。
适应证和用途
COAGADEX，凝血因子X(人)，是一种血浆来源人血凝血因子适用在成年和儿童(年龄12岁和以上)有遗传因子X缺乏为：
• 按需治疗和出血发作的控制
• 有轻度遗传性因子X缺乏患者中出血的围手术处理.
使用的限制
未曽在有中度和严重遗传性因子X缺乏患者研究重大手术出血的围手术处理。
剂量和给药方法
只为重建后静脉使用
⑴ 每小瓶COAGADEX含以国际单位(IU)的标记量因子X。
⑵ 治疗的剂量和时间依赖于因子X缺乏的严重程度，出血的位置和程度和患者的临床情况。
⑶ 为出血发作的治疗：每kg体重使用25IU，间隔24小时重复直至出血停止。
⑷ 为围手术处理：
① 手术前，升高血浆因子X水平至70-90IU/dL。
② 手术后，维持血浆因子X水平在最低50IU/dL直至患者不再处于由于手术出血风险。
③ 所需剂量(IU)=体重(kg)×想要因子X升高(IU/dL或正常的%)×0.5
剂型和规格
COAGADEX是可得到为冰冻干燥粉为重建在一次性使用小瓶含名义上(约) 250 IU或500 IU的因子X活性。当用药盒供应的无菌注射用水重建，最终浓度是约100 IU/mL。
禁忌证
在患者有对COAGADEX或组分的任何有威胁生命超敏性反应不要使用。
警告和注意事项
⑴ 超敏性反应，包括过敏性反应，是可能的。症状发生，终止COAGADEX和给予适当治疗。
⑵ 可能发生中和抗体的发展(抑制剂)。如没有达到预期血浆因子X活性水平，或如用适当剂量不能控制出血，进行分析测定因子X抑制剂浓度。
⑶ COAGADEX是从人血制造和所以携带传播传染病原体，如病毒，变异型克雅氏病[variant Creutzfeldt-Jakob disease(vCJD)]病原体和，理论上，克雅氏病(CJD)病原体。
不良反应
在临床试验中观察到最常见不良药物反应(频数 ≥5%受试者)是输注部位红斑，输注部位疼痛，疲乏和背痛。

Coagadex injection(Coagulation Factor X, Human)
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
Perioperative management of bleeding in major surgery in patients with moderate and severe hereditary factor X deficiency has not been studied.
1. Name of the medicinal product
Coagadex 250 IU powder and solvent for solution for injection.
Coagadex 500 IU powder and solvent for solution for injection.
2. Qualitative and quantitative composition
Each vial contains nominally 250 IU or 500 IU human coagulation factor X.
Coagadex contains 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.
Produced from the plasma of human donors.
Excipients with known effect:
Coagadex contains up to 0.4 mmol/mL (9.2 mg/mL) of sodium.
For the full list of excipients, see section 6.1.
3. Pharmaceutical form
Powder and solvent for solution for injection.
Powder vial containing white or off-white powder.
Solvent vial containing clear colourless liquid.
4. Clinical particulars
4.1 Therapeutic indications
Coagadex is indicated for the treatment and prophylaxis of bleeding episodes and for perioperative management in patients with hereditary factor X deficiency.
4.2 Posology and method of administration
Treatment should be initiated under the supervision of a physician experienced in the treatment of rare bleeding disorders.
Posology
The dose and duration of treatment in adults and children are the same.
The dose and duration of the treatment depend on the severity of the factor X deficiency (i.e. the patient's baseline factor X level), on the location and extent of the bleeding and on the patient's clinical condition. Careful control of replacement therapy is especially important in cases of major surgery or life-threatening bleeding episodes.
Not more than 60 IU/kg daily should be administered.
The expected in vivo peak increase in factor X level expressed as IU/dL (or % of normal) can be estimated using the following formulae:
Dose (IU) = body weight (kg) x desired factor X rise (IU/dL or % of normal) x 0.5
OR
Increase in factor X level (IU/dL or % of normal) = [total dose (IU)/body weight (kg)] x 2
The following examples assume the patient's baseline factor X level is <1 IU/dL:
1. A dose of 2000 IU Coagadex administered to a 70 kg patient should be expected to result in a peak post-infusion factor X increase of 2000 x {[2 IU/dL]/[IU/kg]}/[70 kg] = 57 IU/dL (i.e. 57% of normal)
2. A peak Factor X level of 90% of normal is required in a 40 kg child. In this situation, the appropriate dose would be:
40 kg x 90 IU/dL/{[2 IU/dL]/[IU/kg]} = 1800 IU.
The dose and frequency should be based on the individual clinical response. Patients may vary in their pharmacokinetic (e.g. half-life, in vivo recovery) and clinical responses to Coagadex. Although the dose can be estimated using the calculations above, whenever possible appropriate laboratory tests, such as serial factor X assays, should be performed to guide dose adjustments.
Control and Prevention of Bleeding Episodes
For treatment of bleeding episodes: 25 IU/kg Coagadex should be injected when the first sign of bleeding occurs or just before the expected onset of menstrual bleeding. Repeat at intervals of 24 hours until the bleed stops. Judge each individual bleed on its own severity.
For secondary prophylaxis against re-bleeding or short-term prophylaxis prior to anticipated physical activity or dental appointments: 25 IU/kg Coagadex should be injected and repeat as required.
There are limited data on the use of Coagadex for longer periods of prophylaxis but 24.6 to 28 IU/kg once weekly or 25 IU/kg every two weeks have been used for several weeks or months (see section 5.1).
Perioperative Management
Pre-surgery: calculate dose of Coagadex to raise plasma factor X levels to 70-90 IU/dL. The careful control of dose and duration of treatment is especially important in cases of major surgery.
Required dose (IU) = body weight (kg) x desired factor X rise (IU/dL) x 0.5
The desired factor X rise is the difference between the patient's plasma factor X level and the desired level, and based on the observed recovery of 2 IU/dL per IU/kg.
Example: to raise plasma factor X level from 15 IU/dL to 90 IU/dL in a 70 kg patient, the appropriate dose is:
70 x (90-15) x 0.5 = 2,625 IU.
Post-surgery: dose as necessary to 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.
It is recommended that post-infusion plasma factor X levels are measured for each patient before and after surgery, to ensure that haemostatic levels are obtained and maintained.
Elderly
No dose adjustment is necessary.
Renal impairment
No dose adjustment is necessary.
Hepatic impairment
No dose adjustment is necessary.
Paediatric population
The safety and efficacy of Coagadex in children less than 12 years of age have not yet been established.
Method of administration
Intravenous use.
After reconstitution, the product should be administered by the intravenous route at a suggested rate of 10 mL/min, but no more than 20 mL/min.
For home therapy, the patient should be given appropriate training and reviewed at intervals.
For instructions on reconstitution of the medicinal product before administration, see section 6.6.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
Hypersensitivity
Allergic type hypersensitivity reactions, including anaphylaxis, are possible. Coagadex contains traces of human proteins other than factor X. Patients should be informed of the early signs of hypersensitivity reactions including angioedema, infusion site inflammation (e.g. burning, stinging, erythema), 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. If any of these symptoms occur, they should be advised to discontinue use of the product immediately and contact their physician. In case of shock, the current medical standards for shock treatment should be observed.
Inhibitors
The formation of neutralising antibodies (inhibitors) to factor X is a possible complication in the management of individuals with factor X deficiency.
In general, all patients treated with Coagadex should be carefully monitored for the development of inhibitors by appropriate clinical observations and laboratory tests. If expected factor X activity levels are not attained, or if bleeding is not controlled with an expected dose, perform an assay that measures factor X inhibitor concentration.
Transmissible Agents
Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.
The measures taken are considered effective for enveloped viruses such as HIV, HBV and HCV, and for the non-enveloped viruses HAV and parvovirus B19.
Vaccination against hepatitis A and B in patients who regularly or repeatedly receive human plasma-derived Factor X products may be warranted.
It is strongly recommended that every time that Coagadex is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.
Sodium Content
Coagadex contains up to 0.4 mmol/mL (9.2 mg/mL) of sodium. To be taken into consideration for patients on a controlled sodium diet.
4.5 Interaction with other medicinal products and other forms of interaction
Coagadex is likely to be counteracted by factor Xa inhibitors, direct or indirect. These antithrombotic agents should not be used in patients with factor X deficiency. Coagadex should not be used as an antidote to the effects of direct oral anti-coagulants (DOACs) in patients who do not have factor X deficiency.
4.6 Fertility, pregnancy and lactation
Pregnancy
Due to the rarity of hereditary factor X deficiency, experience regarding the use of Coagadex during pregnancy and breast-feeding is not available. Therefore, Coagadex should be used during pregnancy only if clearly indicated.
Breast-feeding
Due to the rarity of hereditary factor X deficiency, experience regarding the use of Coagadex during pregnancy and breast-feeding is not available. Therefore, Coagadex should be used during breast-feeding only if clearly indicated.
Fertility
Animal reproduction studies have not been conducted with Coagadex.
4.7 Effects on ability to drive and use machines
Coagadex has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
Summary of safety profile
The adverse reactions that occurred in the highest frequency were infusion site erythema, infusion site pain, fatigue, and back pain.
Hypersensitivity or allergic reactions (which may include angioedema, burning and stinging at the infusion site, chills, flushing, generalised urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) have been observed rarely with treatment of other haemophilias and may in some cases have progressed to severe anaphylaxis (including shock). Hypersensitivity reactions, allergic reactions, and anaphylaxis have not been reported in Coagadex clinical trials.
Tabulated list of adverse reactions
The following adverse reactions have been reported in clinical studies involving 18 patients treated with Coagadex. Frequencies have been evaluated according to the following convention: very common (≥1/10 subjects); common (≥1/100 to <1/10). Frequencies of uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000) or very rare (<1/10,000) cannot be estimated from the available data.
List of adverse reactions (ADRs) in 18 treated subjects

MedDRA System Organ Class	Adverse reaction	Frequency
Musculoskeletal and connective tissue disorders	Back pain	Common
General disorders and administration site conditions	Infusion site erythema Fatigue Infusion site pain	Common

Paediatric population
Frequency, type and severity of adverse reactions in children are expected to be the same as in adults.
For safety information with respect to transmissible agents, see section 4.4.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard
4.9 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.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Anti-haemorrhagics, vitamin K and other haemostatics, coagulation factor X, ATC code: B02BD13.
Mechanism of action
Factor X is an inactive zymogen, which can be activated by factor IXa (via the intrinsic pathway) or by factor VIIa (via the extrinsic pathway). Factor X is converted from its inactive form to the active form (factor Xa) by the cleavage of a 52-residue peptide from the heavy chain. Factor Xa associates with factor Va on a phospholipid surface to form the prothrombinase complex, which activates prothrombin to thrombin in the presence of calcium ions. Thrombin then acts upon soluble fibrinogen and factor XIII to generate a cross-linked fibrin clot.
Pharmacodynamic effects
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.
Clinical efficacy
In a multicentre, open-label, non-randomised clinical trial to evaluate the pharmacokinetics, safety and efficacy of Coagadex, 16 subjects (aged 12 years and above) with moderate to severe hereditary factor X deficiency (FX:C < 5 IU/dL) received a dose of 25 IU/kg Coagadex to treat spontaneous, traumatic and menorrhagic bleeding episodes.
The efficacy of Coagadex in treating bleeding episodes was assessed by the subject and/or investigator for each new bleeding episode, using a pre-determined bleed-specific ordinal rating scale of excellent, good, poor and unassessable. Of the 208 bleeding episodes treated with Coagadex, 187 bleeding episodes in 15 subjects were evaluated for efficacy. Ninety eight (53%) were major bleeding episodes, and 88 (47%) were minor bleeds (one bleed was not assessed). Coagadex was considered to be good (7%) or excellent (91%) in treating 98% of bleeding episodes. Of the 187 bleeding episodes in the efficacy analysis, 155 bleeds (83%) were treated with one infusion, 28 bleeds (15%) with two infusions, 3 bleeds (2%) with three infusions and 1 bleed (0.5%) with four infusions. The mean dose per infusion and total dose of Coagadex were 25.4 IU/kg and 30.4 IU/kg, respectively. Four bleeding episodes in two subjects were considered treatment failures. The recommended dose of 25 IU/kg Coagadex to treat a bleed was maintained during the study for 14 of the 16 subjects. The other two subjects used doses up to 30 IU/kg and 33 IU/kg.
A total of 184 infusions of Coagadex were given as a preventative measure. Routine prophylaxis was used by two subjects. One subject used 28 IU/kg once weekly for 8 weeks and, later, 25 IU/kg every 2 weeks for more than 5 months. The other subject used 24.6 IU/kg once weekly for 8.5 months. Neither subject had any bleeds during these periods.
The safety and efficacy of Coagadex for perioperative management was evaluated in five subjects aged 14 to 59 years with mild (n=2), moderate (n=1), and severe (n=2) disease, who underwent a total of seven surgical procedures.
For all surgical procedures, Coagadex was assessed as excellent (no post-operative bleeding, no requirement of blood transfusions, and blood loss was no more than 'as expected') in controlling blood loss during and after surgery. For major surgery, a median of 13 infusions (range 2 to 15 infusions) and a median cumulative dose of 181 IU/kg (range 45 to 210 IU/kg) were required to maintain haemostasis. For minor surgery, a median of 2.5 infusions (range 1 to 4 infusions) and a median cumulative dose of 89 IU/kg (range 51 to 127 IU/kg) were used to maintain haemostasis.
5.2 Pharmacokinetic properties
In a clinical study of Coagadex in subjects with severe or moderate factor X deficiency (basal FX:C <5 IU/dL), the pharmacokinetics of Coagadex were assessed in 16 subjects after administration of a nominal dose of 25 IU/kg. Pharmacokinetic (PK) parameters were calculated from plasma factor X:C (one-stage clotting assay) activity measurements after subtraction of the pre-dose value. Combining IR values for FX:C at the baseline visit (n=16) and the Repeat PK assessment (n=15) gave an overall geometric mean IR of 2.07 IU/dL per IU/kg administered (n=31). Similarly, combining t½ values at the Baseline Visit and the Repeat PK assessment gave an overall geometric mean t½ of 29.36 hours. Systemic exposure to FX:C at the Repeat PK visit (at least 6 months later) was equivalent to that at baseline, since repeat/baseline ratios for all PK parameters were within the range of 90% to 110%.
The mean (CV%) for incremental recovery as 2.08 (18.1). The mean (CV%) maximun plasma concentration (Cmax) was 0.504 (17.2) IU/mL.
The mean (CV%) for area under the curve (AUC 0-144h) was 17.1 (21.0) IU.hr/mL.
Human coagulation factor X is largely retained within the vascular compartment: mean apparent volume of distribution (Vss) was 56.3 (24.0) mL/kg.
The mean (CV%) half-life of human coagulation factor X was 30.3 (22.8) hr and clearance was 1.35 (21.7) mL/kg/hr.
Renal impairment
No pharmacokinetic studies have been conducted but there is no anticipated effect of gender or renal function on the pharmacokinetic profile of Coagadex.
Hepatic impairment
No pharmacokinetic studies have been conducted but there is no anticipated effect of gender or hepatic function on the pharmacokinetic profile of Coagadex.
Elderly
No pharmacokinetic studies have been conducted but there is no anticipated effect of age on the pharmacokinetic profile of Coagadex.
Long-term use
There are limited data on long-term use.
Paediatric population
Pharmacokinetic studies have not been performed in children under the age of 12 years. Data on incremental recovery is limited but appears similar to that seen in the patient population of 12 years of age or older.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, single and repeat-dose toxicity, thrombogenicity and local tolerability.
No investigations on genotoxicity, carcinogenicity and reproductive or developmental toxitcity have been conducted since human plasma coagulation factor X (as contained in Coagadex) is an endogenous protein.
6. Pharmaceutical particulars
6.1 List of excipients
Powder
Citric acid
Sodium hydroxide (for pH adjustment)
Disodium phosphate dihydrate
Sodium chloride
Sucrose
Solvent
Water for injections
6.2 Incompatibilities
In the absence of compatability studies, this medicinal product must not be mixed with other medicinal products.
The product should only be reconstituted using the Mix2Vial that is provided in the pack.
6.3 Shelf life
3 years.
After reconstitution, from a microbiological point of view, the product should be used immediately.
However, chemical and physical in-use stability has been demonstrated for 1 hour at room temperature (up to 25°C +/-2°C).
6.4 Special precautions for storage
Do not store above 30°C.
Do not freeze.
Keep container in the outer carton in order to protect it from light.
For storage conditions after reconstitution of the medicinal product, see section 6.3.
6.5 Nature and contents of container
Immediate containers
Powder vial: 250 IU or 500 IU of human coagulation factor X in a type I glass vial stoppered with a halobutyl rubber stopper, oversealed with a snap-off polypropylene cap and aluminium lacquered skirt.
Solvent vial: 2.5 mL or 5 mL solution in a type I glass vial sealed with a halobutyl rubber stopper and an overseal.
Transfer Device (Mix2Vial).
Pack sizes
Coagadex 250 IU
1 vial 250 IU human coagulation factor X powder for solution for injection
1 vial 2.5 mL water for injections
1 Transfer Device (Mix2Vial)
Coagadex 500 IU
1 vial 500 IU human coagulation factor X powder for solution for injection
1 vial 5 mL water for injections
1 Transfer Device (Mix2Vial)
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
The powder should only be reconstituted with the water for injections provided in the pack. The 250 IU and 500 IU presentations should be reconstituted using 2.5 mL and 5 mL water for injections, respectively.
Do not use the water for injections if signs of particulate matter are visible.
The vials should be brought to room temperature (not above 30°C) prior to the removal of the snap-off cap closure from the powder vial.
Step 1: Remove the cap from the powder vial and clean the top of the stopper with an alcohol swab.
Repeat this step with the solvent vial.
Peel back the top of the transfer device package but leave the device in the package.

Step 2: Place the blue end of the transfer device on the solvent vial and push straight down until the spike penetrates the rubber stopper and snaps into place.
Remove the plastic outer packaging from the transfer device and discard it, taking care not to touch the exposed end of the device.

Step 3: Turn the solvent vial upside down with the transfer device still attached.
Place the clear end of the transfer device on the powder vial and push straight down until the spike penetrates the rubber stopper and snaps into place.

Step 4: The solvent will be pulled into the powder vial by the vacuum contained within it.
Gently swirl the vial to make sure the powder is thoroughly mixed. Do not shake the vial.
A clear or slightly pearl-like solution should be obtained, usually in less than 1 minute (5 minutes maximum).

Step 5: Separate the empty solvent vial and blue part from the clear part by unscrewing anti-clockwise.
Draw air into the syringe by pulling the plunger to the volume of water added. Connect the syringe to the clear part of the transfer device and push the air into the vial.

Step 6: Immediately invert the vial of solution, which will be drawn into the syringe.
Disconnect the filled syringe from the device.
Follow the normal safety practices to administer the medicine.

Note: If you have more than one vial to make up your dose, repeat steps 1 through 6 withdrawing the solution in the vial into the same syringe.
The transfer device supplied with the product is sterile and cannot be used more than once. When the reconstitution process is complete, the used transfer device should be disposed of it in the 'sharps box'.
The solution should be colourless, clear or slightly opalescent when administered. Do not use solutions that are cloudy or have deposits. Reconstituted products should be inspected visually for particulate matter and discolouration prior to administration.
Any unused product or waste material should be disposed of in accordance with local requirements.
7. Marketing authorisation holder
Bio Products Laboratory Limited,
Dagger Lane,
Elstree,
Hertfordshire,
WD6 3BX,
United Kingdom
8. Marketing authorisation number(s)
EU/1/16/1087/001
EU/1/16/1087/002
9. Date of first authorisation/renewal of the authorisation
Date of first authorisation: 16 March 2016
10. Date of revision of the text
Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu
欧盟批准Coagadex用于治疗遗传性X因子缺陷
欧洲药品管理局授予生物产品实验室（BPL）公司的Coagadex上市许可。Coagadex旨在遗传性因子X缺陷患者中用于出血发作的治疗与预防，以及用于围手术期处理。在欧洲，Coagadex是首个也是唯一一个被许可专门用于这种罕见出血性疾病的治疗药物。
因子X缺陷是由于血液中没有充足的因子X蛋白而引起的一种罕见并严重的疾病。因子X蛋白在帮助患者止血的血液凝结中起着关键的作用。有因子X缺陷的人处于出血或经历过多或持续出血的风险中。严重受影响的个体患者通常是儿童，他们脑内、肺内或胃肠道内出血的风险增加，这可能是危及生命的。遗传性因子X缺陷是非常罕见的，这种疾病在欧洲影响大约700名患者。
这款药物对患者来说是一个重大进展
米兰大学IRCCSMaggiore医院内科教授、安吉洛比安奇诺米血友病与血栓形成中心主任Peyvandi教授在评论此次批准时称：迄今为止，我们已通过输注血浆或浓缩的凝血因子专注于治疗因子X缺陷。我们想找到一款特定的因子X治疗药物用以治疗这些脆弱的患者。因此，今天Coagadex在欧盟的批准对患者是一个重大进展。
伦敦圣乔治大学医院NHS信托基金会的血友病中心主任Austin博士补充称：我一直参与Coagadex的临床开发项目，非常高兴这款治疗药物现在已获得批准。患有这种罕见疾病的患者第一次可以获得一款专门的、在临床研究中已被证实安全有效的治疗药物。
该药物的获批基于两项研究
Coagadex的获批基于两项开放式、多中心前瞻性研究数据。第一项研究招募的受试者为有中重度遗传性因子X缺陷的患者，他们因自发或创伤性出血发作而进行按需治疗。研究的主要疗效终点是药动学指标，包括恢复速率和半衰期，次要终点包括疗效总体评价及为治疗出血而需要输注的次数。研究中治疗成功的标准令人满意，药动学参数与先前发布的数据一致。
研究中2名患者报道的6项不良事件被认为可能与药物有关，包括1名患者出现两次疲劳事件，1名患者出现两次输注部位红疹事件，其中1名患者还出现了注射部位疼痛，2名患者均有背部疼痛。无其它药物相关不良事件，无严重药物相关不良事件，无患者因不良事件而中止研究。
第二项研究收集了2名手术前后接受Coagadex治疗的外科患者的数据。加上第一项研究中3名患者的外科数据，这样就有5名患者经历7次手术治疗。对于所有的手术治疗，手术期间及手术后，Coagadex在控制出血方面被研究者评价为出色。
经历重大手术的所有患者被确诊有中度因子X缺陷。1名中度缺陷及2名严重缺陷患者经历了小手术。中重度疾病患者未经历大手术。第二项研究中，外科患者未报道有治疗相关的不良事件。两项研究中，最常见的不良事件是输注部位红疹、输注部位疼痛、疲劳及背部疼痛。