英国制药公司Shire是罕见病领域的全球生物技术领导者。近日，该公司研发的一款血友病疗法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）已发布积极意见，推荐批准Adynovi（抗血友病因子[重组]，聚乙二醇化），用于12岁及以上青少年及成人A型血有病患者的按需治疗（on-demand use）及预防性治疗（prophylactic use）。欧盟委员会（EC）在做出最终审查决定时通常都会采纳CHMP的建议，这也意味着，Adynovi很有可能在未来2-3个月内获批。如果上市，Adynovi将为A型血友病患者群体提供一种一周2次的预防性治疗选择。

Adynovi最初由Baxalta研发，该公司是百特国际（Baxter International）于2015年拆分并上市的生物制药公司，继承了百特全部的血液疾病产品、肿瘤药物、免疫疾病药物。Shire于2016年初豪掷320亿美元收购Baxalta，进一步奠定了罕见病领域的领先地位。

Adynovi是基于百特已上市产品ADVATE研发的一种半衰期延长的重组凝血因子VIII（rFVIII），开发用于A型血液病的治疗。ADVATE是百特的龙头产品，上市时间超过10年，是全球处方量最多的FVIII产品。

Adynovi是ADVATE的长效版，采用了新型聚乙二醇化技术延长药物在体内的循环半衰期，该药将为A型血友病患者提供一种重要的新治疗选择。在美国，该药于2015年11月获FDA批准，以品牌名Adynovate上市销售，用于A型血有病青少年（12岁以上）和成人患者的预防性治疗（降低出血频率）、按需治疗及出血控制。

与未经修饰的抗血友病因子相比，Adynovi/Adynovate在血液中能持续更久，用药时间间隔更长，将为治疗A型血有病及减少出血频率提供更可靠的治疗选择。值得一提的是，在美国，该药也是第10个被批准上市的重组VIII因子。

Adynovi上市许可申请（MAA）的提交，是基于3个III期临床研究的数据，包括：（1）在12-65岁A型血有病群体中开展的一项前瞻性、全球性、多中心、开放标签、非随机III期研究；（2）在12岁及以下重度A型血液病儿科患者中开展的一项前瞻性、非对照、开放标签、多中心III期研究；（3）一项在15例接受外科手术治疗的重度A型血液病中评估Adynovi用于围手术期止血的疗效和安全性III期研究。这些研究数据已于2015年12月公布。

A型血有病是一种X染色体连锁的凝血因子VIII量和分子结构异常引起的隐性遗传性出血性疾病，多发于男性。该病通常是由体内VIII因子缺乏引起，可引起关节点的反复出血，从而导致关节严重受损。在欧盟，A型血友病是一种罕见性疾病。当前，该病影响全球超过15万人，其中大约75%的患者未能接受充分治疗或获取到药物治疗。

Active Substance: rurioctocog alfa pegol 
Common Name: rurioctocog alfa pegol 
ATC Code: B02BD02
Marketing Authorisation Holder: Baxalta Innovations GmbH
Active Substance: rurioctocog alfa pegol 
Status: Authorised
Authorisation Date: 2018-01-08
Therapeutic Area: Hemophilia A
Pharmacotherapeutic Group: Antihemorrhagics

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

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

Adynovi contains the active substance rurioctocog alfa pegol.

Adynovi 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.

Adynovi is available as a powder and solvent that are mixed together to make a solution for injection into a vein. The dose and frequency of treatment depend on whether it is used to treat or prevent bleeding, as well as on the seriousness of the haemophilia, the extent and location of the bleeding and the patient’s condition and bodyweight. Patients or their carers may be able to inject Adynovi themselves at home once they have been trained appropriately.

For further details, see the package leaflet.

Patients with haemophilia A lack factor VIII, a protein needed for normal clotting of the blood, and as a result, they bleed readily. The active substance in Adynovi, rurioctocog alfa pegol, works in the body in the same way as human factor VIII. It replaces the missing factor VIII, thereby helping the blood to clot and giving temporary control of the bleeding disorder.

Adynovi has been shown in two main studies to be effective at preventing and treating bleeding episodes in patients with severe haemophilia who were previously treated with other factor VIII products.

In a study involving 138 adults and adolescents aged 12 years or above, 120 patients given Adynovi as a twice-weekly preventive treatment had, on average, around 4 bleeding episodes a year, and 17 patients given Adynovi for treating bleedings ‘on demand’ had around 43 bleeding episodes a year. In addition, when bleeding did occur, Adynovi was rated excellent or good at treating around 96% of bleeding episodes. Around 96% of bleeding episodes resolved with one or two injections of Adynovi.

In the second study in 66 children aged below 12 years, all patients were given Adynovi as a twice-weekly preventive treatment for around 6 months. During this period, around 38% of patients (25 out of 66) had no bleeding episodes, and none of the patients developed antibodies against Adynovi, which can cause the medicine to stop working. When bleeding occurred, Adynovi was rated excellent or good at treating around 90% of episodes. Around 83% of bleeding episodes resolved with one injection.

Hypersensitivity (allergic) reactions are uncommon with Adynovi (affecting up to 1 in 100 people) 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 rapid heartbeat, tightness of the chest and wheezing. In some cases these reactions can become severe.

Following treatment with factor VIII products, including Adynovi, some patients may develop inhibitors (antibodies) against factor VIII, causing the medicine to stop working and resulting in a loss of bleeding control. In such cases, a specialised haemophilia centre should be contacted.

For the full list of all side effects see the package leaflet.

Adynovi must not be used in patients who are hypersensitive (allergic) to rurioctocog alfa pegol or the related substance octocog alfa or to any of the other ingredients of the medicine, nor in those with known allergy to mouse or hamster proteins.

The European Medicines Agency decided that Adynovi’s benefits are greater than its risks and recommended that it be approved for use in the EU. Studies show that Adynovi is effective at preventing and treating bleeding episodes in patients with haemophilia A and its safety is comparable to that of other factor VIII products. However, part of the active substance in Adynovi (called PEG) may accumulate in the body, including in a structure in the brain called the choroid plexus, following long-term treatment. Since this could potentially cause problems especially in children below 12 years of age, Adynovi is only approved for use in adults and children from 12 years of age.

The company that markets Adynovi 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 Adynovi have also 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 Adynovi on 8 January 2018.

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