Zalmoxis(TK cell therapy)胸苷激酶细胞治疗

通用名：TK细胞疗法
商品名称：Zalmoxis

别名：HSV-TK; TBI-0301;胸苷激酶细胞治疗

TK细胞治疗急性白血病病人，造血干细胞移植 - 辅助治疗

TK细胞疗法旨在被用作一种辅助疗法用于急性白血病患者谁是候选人为造血干细胞移植（HSCT）和缺少合适的人类白细胞抗原匹配供体的治疗。如果许可，则有可能减少移植相关的死亡率，白血病复发和减少需要移植后的免疫抑制的潜力。 TK细胞疗法是一种免疫刺激产品的基础上，从一个供体的T细胞，从单倍体 - 相同供体潜在地有利的更安全的造血干细胞移植。

在英国，大约有2600名成人被诊断为急性白血病，无论是髓系（AML）或淋巴细胞（ALL），每年都有。在欧洲，8752白血病相关的造血干细胞移植的操作在2009年进行的，8022（92％）的同种异体和730（8％），自体的。据该公司HSCT患者的50％提供了信息，将有资格和可能的TK细胞治疗中获益。在英国，749无关供者造血干细胞移植在2009年进行比较，在2001年301。
急性白血病可以与一系列化学疗法，放射疗法，化学疗法或与干细胞移植治疗。

TK细胞治疗是目前比较其对急性白血病结合对单独半相合HCT半相合HCT影响的III期临床试验。该试验预计将在2016年6月报告。

 MolMed宣布其Zalmoxis获得欧盟的有条件上市许可。Zalmoxis是第一个作为血液系统恶性肿瘤经过haplo-identical HSCT(单倍相合造血干细胞移植)治疗的特异性辅助治疗的基因免疫疗法。

       Zalmoxis这种新奇的疗法通过基因工程，使供体免疫系统T细胞携带可诱导的'自杀基因'。当经过造血干细胞移植后，对患者进行给药，这些细胞一方面能消除移植后的免疫抑制作用，另一方面又迅速免疫重建。通过这种'自杀基因'技术，这些细胞就产生了抗白血病效应。这些自杀基因很容易把控单倍相合造血干细胞移植后的移植物抗宿主反应。Zalmoxis显著增加了长期生存期，从而使经过部分相容的造血干细胞移植的治疗更加安全和有效。

       Zalmoxis的产品特性概要(SmPC)将包括完整的处方信息(包括Zalmoxis的安全性、有效性以及欧盟批准的适应症)。SmPC将在欧盟公共评估报告(EPAR)中发表。

据估计，欧洲每年大约1.3万高危血液系统恶性肿瘤患者进行单倍相合造血干细胞移植，而且年增长率达30%。此外，大约11万的高危血液系统恶性肿瘤患者缺乏一个完全兼容的捐助者，对此，Zalmoxis可能提供了一个可行的治疗方法。

       此次上市批准依据的是临床I-II期以及正在进行的关键临床III期的安全性和有效性数据。

       MolMed是一家专注于研究、开发新型抗癌疗法的医药生物技术公司。MolMed 管线包括： 第一个，Zalmoxis® (TK)是一种细胞为基础的基因免疫疗法，主要针对高危的血液系统恶性肿瘤。

第二个，NGR-hTNF，一种新型的治疗实体瘤的药物，目前，显示出有抗肿瘤活性。第三个，CAR-CD44v6，一种基因免疫疗法，可能对许多血液系统恶性肿瘤和几个上皮肿瘤有效，目前处于临床前。

Information 
Generic Name: TK cell therapy  
Trade Name: Zalmoxis  
Synonym: HSV-Tk; TBI-0301; Thymidine kinase cell therapy   
Entry Type: Cell-based therapy   
Developmental Status 
UK: Pre-registration (Filed)  
EU: Pre-registration (Filed)  
US: Phase III Clinical Trials  
UK launch Plans: Available only to registered users 
Actual UK launch date:   
Comments 
Apr 14: The application to the FDA for TK cell therapy for adjunctive treatment in HSCT for adult pts with high-risk acute leukaemia had been refused. The FDA suggested that the application can be resubmitted when new clinical evidence is available. [7] 
02/04/2014 12:47:02 
TK therapy was granted Orphan Drug Designation (EU/3/10/773) in the EU in Sep 10 [6] 
14/03/2014 18:59:00 
Mar 14: An application for Conditional Marketing Authorisation for TK has been filed in the EU as an adjunctive treatment in hematopoietic stem cell transplantation (HSCT) for patients affected by high risk leukaemia. The application is supported by efficacy and safety results obtained from a completed PI/II multicentre trial (TK007) and supported by initial data from the ongoing randomised PIII study (TK008) [5]. 
14/03/2014 18:53:39 
Mar 13: MolMed reports it has begun preparing its regulatory dossier to support Conditional Marketing Approval in the EU, based on safety & efficacy data obtained from more than 120 patients in its ongoing PIII trial. The company expects to submit its request for approval of TK cell therapy to treat leukaemia to the EMA by mid-2013 [2]. 
13/05/2013 11:32:49 
Trial or other data 
Under a licence agreement with Oxford BioMedica, MolMed´s TK therapy product employs Oxford BioMedica´s retroviral ex vivo gene delivery technology [2]. 
13/05/2013 11:49:04 
Apr 13: The company announces it is expanding production capacity to support the ongoing PIII trial & future commercialisation of the TK cell therapy product [2]. 
13/05/2013 11:48:56 
Feb 13: Positive results reported following analysis of data from 611 pts in Italy over eight years, including pts from the PII TK007 (NCT00423124) & PIII TK008 (NCT00914628) trials. The results indicated that overall & disease-free survival was comparable between pts who had received fully matched or partially match bone marrow transplants [2]. 
13/05/2013 11:47:26 
Aug 12: MolMed announces that, in order to increase the recruitment rate in its PIII trial of TK cell therapy, it would start enrolling patients with more advanced disease. The trial is comparing TK cell therapy with a standard T cell repletion strategy, in reducing non-relapse mortality following (haplo-HSCT in pts with acute high-risk leukaemia (TK 008; NCT00914628; EudraCT 2009-012973-37). The trial is intended to enrol 170 pts and is recruiting in the US, Italy, Belgium, France, Germany, Greece, the Netherlands & Spain. MolMed received clearance from the US FDA to expand recruitment in the trial to sites in the US, following submission of an IND in Nov 2010. Primary analysis of results is expected in 2013 [2]. 
13/05/2013 11:42:46 
Jun 10: Positive results from a PII study (NCT00423124) reported at ASCO-2010. The trial enrolled 57 pts in Germany, Greece, Israel, Italy, & the UK. The trial involved haplo-SCT, followed by the TK cell therapy for patients with high risk haematological malignancies (including ALL & AML) [2]. 
13/05/2013 11:41:30 
TK cell therapy is administered once at 21 days after HSCT, and then up to three times subsequently [1]. 
13/05/2013 11:34:42 
TK-based cell therapy (herpes simplex virus thymidine kinase donor lymphocytes; HSV-TK) is an immunostimulant product based on T cells from a donor, potentially enabling safer HSCT from haploidentical donors. TK cell therapy consists of donor T cells genetically engineered ex vivo to express HSV-TK, making these cells sensitive to the antiviral drug ganciclovir. This modification reduces the risk of Graft versus Host Disease (GvHD) and preserves the protection against infection and disease relapse provided by donor T cells. In addition, there is no need for post-transplant immuno-suppression. TK cell therapy may therefore increase the effectiveness of HSCT in pts who do not have a fully compatible donor [1]. 
13/05/2013 11:34:10 
Evidence Based eva luations 
NHSC/NIHR  http://www.hsc.nihr.ac.uk/files/downloads/2027/2366.05105aff.TKcellth

erapy_Mar13.pdf 
References   
Available only to registered users 
Category 
BNF Category: Other immunomodulating drugs (08.02.04) 
Pharmacology: A thymidine kinase (TK)-based cell therapy involving genetically engineered haplo-identical (allogenic) T lymphocytes in pts undergoing SCT with partially compatible family donors, known as haplo-identical Haematopoietic Stem Cell Transplantation.   
Epidemiology: The incidence of AML is 3.7 per 100,000 people; the incidence of CLL is 1 per 100,00 people [4].   
Indication: Acute lymphoblastic leukaemia (ALL)  
Additional Details: & AML - in pts having HSCT but without a matched donor  
  
Method(s) of Administration   
Intravenous infusion  
  
Company Information 
Name: MolMed  
US Name: MolMed  
  
NICE Information 
In timetable: No