丹麦制药巨头诺和诺德（Novo Nordisk）长效凝血因子IX产品Refixia（nonacog beta pegol，N9-GP）近日在欧盟监管方面传来喜讯。欧洲药品管理局（EMA）人用医药产品委员会（CHMP）发布积极意见，推荐批准Refixia用于B型血友病青少年及成人患者的治疗。

具体而言，CHMP推荐批准Refixia作为一种预防性药物和按需治疗药物，用于12岁及以上青少年和成人B型血友病患者，预防和控制出血事件，以及围术期（手术）管理。

Refixia是一种糖基聚乙二醇化的重组凝血因子IX，具有显著延长的半衰期，同时具有显著改善的药代动力学（PK）属性，该药旨在作为一种替代疗法用于B型血有病的治疗。糖基聚乙二醇化是一种有效延长半衰期的技术，在A型血液病及其他治疗领域已被证明安全有效。

CHMP推荐批准Refixia，是基于Paradigm临床项目的数据，该项目涉及115例重度或中重度B型血液病患者。临床数据显示，Refixia用于B型血友病成人、青少年、儿童患者的常规预防性治疗、出血发作控制、围手术期管理均非常有效，同时耐受性、安全性良好。

与标准的凝血因子IX产品相比，Refixia的半衰期延长了5倍之多。在Paradigm临床项目中，尽管Refixia给药的频率较低，但患者血液中Refixia却达到了较高的水平。在III期临床中，每周一次用药40 IU/kg Refixia所维持的因子IX活性水平高于15%，同时将平均年出血率（ABR）降低至1.0，并且表现出预防目标关节出血的潜力。此外，这些患者在整个研究过程中生活质量也得到了显著改善。

诺和诺德执行副总裁及首席科学官Mads Krogsgaard Thomsen表示，非常高兴Refixia获得了欧盟CHMP推荐批准的积极意见，这标志着该公司在致力于扩大血液病患者治疗选择方面所取得的一个重要里程碑。该公司相信，Refixia所具有的强大临床证据，将帮助B型血液病患者群体更好地预防出血以及预防关节受损。

B型血友病是一种罕见的遗传性血液疾病，患者体内先天性缺乏凝血因子IX，导致凝血障碍。据估计，全球范围内大约有2.6万例B型血液病患者。目前，该病的治疗需要反复静脉输注血浆来源的或重组的因子IX，来控制和预防出血发作。

诺和诺德表示，Refixia作为一种新的长效因子IX产品，具有较高的因子IX活性水平、较低的用药频率、同时可减少出血率，该药有望大幅改善B型血液病患者及其家庭成员的生活质量

Refixia

Active Substance: nonacog beta pegol 
Common Name: nonacog beta pegol 
ATC Code: B02BD04
Marketing Authorisation Holder: Novo Nordisk A/S
Active Substance: nonacog beta pegol 
Status: Authorised
Authorisation Date: 2017-06-02
Therapeutic Area: Hemophilia B
Pharmacotherapeutic Group: Antihemorrhagics

Treatment and prophylaxis of bleeding in patients 12 years and above with haemophilia B (congenital factor IX deficiency).

Refixia is a medicine used to treat and prevent bleeding in patients with haemophilia B, an inherited bleeding disorder caused by lack of a clotting protein called factor IX. It can be used in adults and children from 12 years of age.

Refixia contains the active substance nonacog beta pegol.

Refixia can only be obtained with a prescription and treatment should be under the supervision of a doctor who has experience in the treatment of haemophilia.

Refixia is available as a powder and a liquid that are mixed together to make a solution for injection into a vein. The dose and frequency of treatment depend on whether Refixia is used to treat or prevent bleeding, or to reduce bleeding during surgery, the extent and location of the bleeding, and the patient’s bodyweight. For further information on how to use this medicine, see the summary of product characteristics (also part of the EPAR).

Patients or their carers may be able to inject Refixia themselves at home once they have been trained appropriately. For full details, see the package leaflet.

Patients with haemophilia B lack factor IX, a protein needed for normal clotting of the blood, and as a result, they bleed readily. The active substance in Refixia, nonacog beta pegol, works in the body in the same way as human factor IX. It replaces the missing factor IX, thereby helping the blood to clot and giving temporary control of bleeding.

Refixia has been shown to be effective at both treating bleeding episodes and keeping the number of episodes low.

In a study involving 74 adults and adolescents aged 13 or above, 29 patients given Refixia as a weekly preventive treatment had around 1 bleeding episode a year, and 15 patients given Refixia for treating bleedings ‘on demand’ had around 16 bleeding episodes a year. In addition, when bleeding did occur, Refixia was rated excellent or good at treating around 92% of bleeding episodes. 87% of bleeding episodes resolved with one injection of Refixia.

In the second study in 25 children aged below 13 years, all patients were given Refixia as a weekly preventive treatment. Patients had around 1 bleeding episode per year and Refixia was rated excellent or good at treating around 93% of bleeding episodes. Around 86% of bleeding episodes resolved with one injection.

Hypersensitivity (allergic) reactions are uncommon with Refixia (may affect up to 1 in 100 patients) and may include: swelling, burning and stinging at the injection site, chills, flushing, itchy rash, headache, hives, low blood pressure, lethargy, nausea and vomiting, restlessness, a fast heartbeat, tightness of the chest and wheezing. In some cases these reactions can become severe.

Some patients taking factor IX medicines may develop inhibitors (antibodies) against factor IX, causing the medicine to stop working and resulting in a loss of bleeding control. Factor IX medicines can also potentially cause problems due to the formation of blood clots in the blood vessels.

Refixia must not be used in patients allergic to hamster proteins. For the full list of side effects and restrictions, see the package leaflet.

The Agency’s Committee for Medicinal Products for Human Use (CHMP) decided that Refixia’s benefits are greater than its risks and recommended that it be approved for use in the EU.

Studies show that Refixia is effective at preventing and treating bleeding episodes in patients with haemophilia B and its safety is comparable to that of other factor IX products. However, part of the active substance in Refixia (called PEG) may accumulate in the body, including in a structure in the brain called choroid plexus, following long-term treatment. Since this could potentially cause problems especially in children below 12 years of age, Refixia is only approved for use in in adults and children from 12 years of age.

The company that markets Refixia will conduct a study to investigate the potential effects of PEG accumulation in the choroid plexus of the brain and other organs.

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Refixia have been included in the summary of product characteristics and the package leaflet.

The European Commission granted a marketing authorisation valid throughout the European Union for Refixia on 02 June 2017.

For more information about treatment with Refixia, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.