The European Commission granted a marketing authorization valid throughout the European Union for Zalmoxis on 18 August. Zalmoxis is a medicine used as an add-on treatment in adults with leukaemias and lymphomas who have received a haploidentical haematopoietic stem cell transplant. Zalmoxis is an advanced therapy medicine called a ‘somatic cell therapy product’. It contains T cells from the HSCT donor that have been genetically modified to include a ‘suicide gene’. In detail Zalmoxis contains allogenic T cells genetically modified with a retroviral vector encoding for a truncated form of the human low affinity nerve growth factor receptor (ΔLNGFR) and the herpes simplex I virus thymidine kinase (HSV-TK Mut2).
Because the number of patients undergoing haploidentical HSCT is low, in 2003 it was designated as an ‘orphan medicine’.
Zalmoxis is prepared for use in a specific patient. It is given 21 to 49 days after transplantation, but only if the transplant has not already restored the patient’s immune system and if the patient has not developed graft-versus-host disease. It helps the patient to build up their immune system and so helps to protect them from infections. However the T cells in Zalmoxis can sometimes attack the patient’s body, causing graft-versus-host disease. The T cells in Zalmoxis have a suicide gene, which makes them susceptible to the medicines ganciclovir and valganciclovir. If the patient develops graft-versus-host disease, ganciclovir or valganciclovir is given, which kills the T cells that have the suicide gene thereby treating the disease and preventing its further development.
Zalmoxis has been investigated in a main study involving 30 patients who had haploidentical HSCT for serious blood cancers. In this study, Zalmoxis was not compared with any other treatment. The main measure of effectiveness was restoration of the immune system as measured by blood levels of T cells. 77% of the patients receiving Zalmoxis (23 out of 30) had their immune systems restored. Graft-versus-host disease occurred in 10 patients who were then given ganciclovir or valganciclovir, either alone or in combination with other medicines. All 10 patients recovered from graft-versus-host disease.
Data from the main study were also combined with data from a second ongoing study, and survival rates for 37 patients treated with Zalmoxis (23 from the main study and 14 from the ongoing study) were compared with rates from a patient database of 140 patients who have undergone haploidentical HSCT in the past. The number of patients who survived after one year was 51% for patients who received Zalmoxis compared with 34 to 40% for patients who did not receive Zalmoxis.
Zalmoxis has been given ‘conditional approval’. This means that there is more evidence to come about the medicine, which the company is required to provide.
There is an ongoing study in high-risk acute leukaemia patients. The study will compare haploidentical HSCT followed by treatment with Zalmoxis with haploidentical HSCT containing T cells followed by treatment with cyclophosphamide (a medicine to prevent graft-versus-host disease) and with haploidentical HSCT without T cells.