Date: 2015-12-10
Type of information: Publication of results in a medical journal
phase: 1-2
Announcement: publication of results in Science Translational Medicine
Company: MolMed (Italy)
Product: Zalmoxis® - investigational cell therapy product TK
Action
mechanism: gene therapy/cell therapy. TK is an investigational cell therapy product, based on the use of genetically engineered donor T cells in association with bone marrow transplants from healthy donors, and particularly from partially compatible family donors (haplo2 transplants), for the cure of high-risk leukaemia. Add-backs of TK has the potential to allow the retention of immune-protection and anti-leukaemia effects of donor T cells, while promptly controlling and abrogating the possible onset of GvHD. The TK product has been granted Orphan Drug designation in both the EU and the US.
Disease: high risk leukemia
Therapeutic area: Cancer - Oncology
Country: Germany, Grece, Israel, Italy, UK
Trial details:
Latest
news: * On December 10, 2015, MolMed announced that results of the study titled “Tracking genetically engineered lymphocytes long-term reveals the dynamics of T-cell immunological memory”, conducted on patients enrolled in the MolMed’s Phase I/II TK007 clinical trial, have been published in Science Translational Medicine. Researchers and clinicians of IRCCS San Raffaele Hospital in Milan carried out the study and Dr. Giacomo Oliveira, first author of the publication, presented the outcomes during the last American Society of Hematology (ASH) Annual Congress, held in Orlando between the 5th and 8th of December, 2015. The study investigated immune cells of patients with acute high-risk leukaemia, enrolled in the TK007 clinical
trial, who, between 1995 and 2012, underwent haplo-identical hematopoietic stem cell transplantation (haploHSCT) and infusion of donor memory T cells, transduced to express the TK suicide gene (Zalmoxis®). Patients’ immunologic parameters analysis detected TK cells, characterized them and unravelled the requirements for their long-term persistence.
Ten adult patients were studied, in three the suicide gene TK was activated in order to abrogate the graft versus host disease (GvHD) which set in early after the haplo-HSCT. At a follow-up period in the range of 2 to 14 years, all patients were in complete remission, free of GvHD and with a normal immune system. Furthermore, TK cells were detected in all patients, armed with a still functioning suicide gene. Analysis of the patients’ immune system and of the single engineered TK cells allowed scientists to unravel that memory T cells of “stem” phenotype and having been exposed to the antigen are the most capable to expand and to persist long term.
* On December 10, 2012, MolMed has announced the presentation of the long term clinical benefit and safety data of its investigational cell-based therapy TK at the 54th Annual Meeting of the American Society of Hematology (ASH). The overall analysis comprises 128 patients with high-risk haematological malignancies who were treated in different countries in 10 Phase I-II clinical trials with TK cells, i.e. genetically engineered donor T cells administered after haematopoietic stem cell transplants from healthy donors to improve the graft-versus leukaemia effect and to hasten patient immune reconstitution. Notably, no adverse events correlated to the use of TK cells were ever reported. Graft versus Host Disease (GvHD) was reported in 28 patients which, in all cases was rapidly and completely controlled thanks to the TK technology without the need of high-dose immunosupression following the transplant. These results confirm the feasibility, safety and effectiveness of this approach on a large patient population.
Most importantly, 34 patients – predominantly enrolled in MolMed’s Phase I/II study TK007 – who did not find a fully-compatible donor and received TK cells from a partially-compatible (haplo-identical) donor. Out of those, 25 patients quickly achieved immune reconstitution and nine patients are alive and completely disease-free after a median follow-up of 7 years. Also in these patients GvHD, when occurring, was always controlled thanks to the TK technology without the need of further pharmacological treatment.
These long-term clinical data are relevant in light of the severe disease status and the advanced age of the patient population treated. The results further confirm the overall high benefit/risk ratio of the TK cell therapy and, most relevantly, outline its potential for curing high-risk patients.
MolMed is conducting an international pivotal randomised Phase III trial for high-risk leukaemia patients undergoing bone marrow transplants from haplo-identical donors, ongoing in Europe and the US. Moreover, based on this accumulated data and the rarity of the indication (TK has obtained Orphan Drug designation), the Company expects to file a request for Conditional Marketing Authorisation to the European Authority in mid-2013.
