New Medicines

ZalmoxisHigh-risk haematological malignancies - adjunctive treatment in haploidentical haematopoietic stem cell transplantation (HSCT) of adults


New molecular entity
Dompe farmaceutici

Development and Regulatory status

Licence withdrawn
Licence withdrawn
Feb 20The EU marketing authorisation for Zalmoxis has been withdrawn at the request of the marketing authorisation holder as it intends to permanently discontinue the marketing of the product for commercial reasons [13].
Jan 19Zalmoxis is available in Italy and Germany, costing ~300K euros/patient [11].
Jul 17Dompe acquires license and distribution rights to thymidine kinase cell therapy in European Economic Area (EEA) [9].
Nov 16TK therapy was granted Orphan Drug Designation (EU/3/03/168) in the EU in Oct 03 [6].
Aug 16EC has granted a Conditional Marketing Authorisation for Zalmoxis, the first immunogene therapy, as patient-specific adjunctive treatment in haplo-identical haematopoietic stem-cell transplantation (HSCT) for adult patients with high-risk haematological malignancies [8].
Jun 16EU positive opinion for use as adjunctive treatment in haploidentical haematopoietic stem cell transplantation (HSCT) of adult patients with high-risk haematological malignancies [7].
Mar 14An 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].
Mar 13MolMed 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. The company expects to submit its request for approval of TK cell therapy to treat leukaemia to the EMA by mid-2013 [2].


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.
The incidence of AML is 3.7 per 100,000 people; the incidence of CLL is 1 per 100,00 people [4].
High-risk haematological malignancies - adjunctive treatment in haploidentical haematopoietic stem cell transplantation (HSCT) of adults
Intravenous infusion

Trial or other data

Dec 19No UK trial sites [12]
Apr 16PIII (NCT00914628) study is still recruiting [10].
May 13TK cell therapy is administered once at 21 days after HSCT, and then up to three times subsequently [1].
May 13TK-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].
Apr 13Under a licence agreement with Oxford BioMedica, MolMed´s TK therapy product employs Oxford BioMedica´s retroviral ex vivo gene delivery technology [2].
Apr 13The company announces it is expanding production capacity to support the ongoing PIII trial & future commercialisation of the TK cell therapy product [2].
Feb 13Positive 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].
Aug 12MolMed 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].
Jun 10Positive 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].

Evidence based evaluations