What is Zalmoxis and what is it used for? - Genetically modified lymphocytes?
Zalmoxis is a medicine used as an adjunctive treatment in adult patients undergoing hematopoietic stem cell transplantation (HSCT, a cell transplant that can develop into different types of blood cells) from a partially compatible donor (a so-called haploidentical transplant). Zalmoxis is used in patients who have had haploidentical transplantation due to severe blood cancer, such as some leukemia and lymphoma. Before receiving a transplant, the patient will have received treatment to remove existing cells from the bone marrow, including cancer cells and immune system cells. Zalmoxis is given to help restore the patient's immune system after the transplant.
Zalmoxis is a type of advanced therapy medicine called a "somatic cell therapy product", which is a type of medicine containing cells or tissues that have been manipulated so that they can be used to treat, diagnose or prevent a disease. Zalmoxis contains T lymphocytes (a type of white blood cell) that have been genetically modified1. To obtain Zalmoxis, the T lymphocytes from the transplant donor are separated from the rest of the cells in the transplant. These T lymphocytes are then genetically modified to include a "suicide gene".
Since the number of patients underwent low hematopoietic stem cell transplantation (HSCT), Zalmoxis was designated an "orphan medicine" (a medicine used in rare diseases) on 20 October 2003.
How is Zalmoxis used - Genetically modified lymphocytes?
Zalmoxis can only be obtained with a prescription and treatment should be performed under the supervision of a doctor experienced in the treatment of blood cancers using hematopoietic stem cell transplantation (HSCT).
Zalmoxis is prepared for use as a patient-specific medicine. It is administered after a period of 21-49 days from transplantation, but only if the transplant has not already restored the patient's immune system and if the patient has not developed the transplant disease against the host (which occurs when the transplanted cells attack the body).
Zalmoxis is administered by intravenous infusion (drip) for a duration of 20-60 minutes, every month for up to four months, until the circulating T lymphocytes reach a certain level. The dose of Zalmoxis depends on the patient's body weight.
For more information, see the package leaflet.
How does Zalmoxis - genetically modified lymphocytes work?
When administered after the transplant, Zalmoxis helps the patient build the immune system and therefore helps protect it from infection. However the T lymphocytes present in Zalmoxis can sometimes attack the patient's body, causing transplant disease against the host. T cells in Zalmoxis have a suicidal gene, which makes them susceptible to the medicinal products ganciclovir and valganciclovir. If the patient develops the transplant disease against the host, ganciclovir or valganciclovir is administered, which kills the T lymphocytes that have the suicide gene thus treating the disease and preventing further development.
What benefit has Zalmoxis shown - genetically modified lymphocytes during the studies?
Zalmoxis was studied in one main study involving 30 patients who underwent haploidentical transplantation due to severe blood cancer. Zalmoxis was not compared with other therapies in this study. The main measure of effectiveness was the restoration of the immune system as measured by blood levels of T lymphocytes. In 77% of patients treated with Zalmoxis (23 out of 30) the immune system was restored. Host transplantation disease occurred in 10 patients who were then given either ganciclovir or valganciclovir, alone or in combination with other medicines. All 10 patients recovered from the transplant disease against the host.
Data from the main study were also combined with data from a second ongoing study and survival rates for the 37 patients treated with Zalmoxis (23 in the main study and 14 in the current study) were compared with those from a database of 140 patients who have undergone haploidentical transplantation in the past. The percentage of patients who survived after one year was 51% for patients who received Zalmoxis compared with 34-40% for patients who did not receive Zalmoxis.
What are the risks associated with Zalmoxis - Genetically modified lymphocytes?
The most common side effect of Zalmoxis (which can occur in more than 1 in 10 patients) is acute transplant disease against the host (a condition that develops within about 100 days of transplantation). When using Zalmoxis, this condition can be treated with ganciclovir or valganciclovir. Zalmoxis should not be given to patients whose immune system has been restored. Furthermore, it should not be used in patients who have already developed the transplant disease against the host requiring treatment. For the full list of restrictions and side effects reported with Zalmoxis, see the package leaflet.
Why has Zalmoxis - Genetically modified lymphocytes been approved?
Zalmoxis has been shown to help restore the immune system of patients who have undergone haploidentical transplantation due to severe blood cancers; these patients have limited therapeutic options and have a poor prognosis. The safety profile of Zalmoxis is considered acceptable. The main risk is transplant disease against the host, however this can be successfully treated with ganciclovir or valganciclovir, which kills the T lymphocytes present in Zalmoxis. The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that although additional data are needed to determine its extent, the benefits of Zalmoxis outweigh its risks and recommended that it be approved for use in the EU . Zalmoxis has obtained a "conditional approval". This means that further information on the medicine, which the company is required to provide, will be available in the future. Every year the European Medicines Agency will review the new information available and this summary will be updated accordingly.
What information is still awaited for Zalmoxis?
Since Zalmoxis has obtained a "conditional approval", the company that markets Zalmoxis will provide the results of an ongoing study conducted on patients with high-risk acute leukemia. The study will compare the haploidentical transplant followed by treatment with Zalmoxis with haploidentical T-cell transplantation followed by treatment with cyclophosphamide (a medicine to prevent the onset of transplant disease against the host) and with haploidentical transplantation without T lymphocytes.
What measures are being taken to ensure the safe and effective use of Zalmoxis - Genetically modified lymphocytes?
The company that markets Zalmoxis will provide training material for healthcare professionals, with detailed information on the risks, including transplant disease against the host, and how to use the medicine correctly. The company will also collect data from all patients treated with Zalmoxis by filling in a register and will monitor progress after treatment to study the safety and efficacy of the drug in the long term.
Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Zalmoxis have also been included in the summary of product characteristics and the package leaflet.
More information on Zalmoxis - Genetically modified lymphocytes
The full EPAR for Zalmoxis can be found on the Agency's website: ema.europa.eu/Find medicine / Human medicines / European public assessment reports. For more information on Zalmoxis therapy, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.
The summary of the opinion of the Committee for Orphan Medicinal Products related to Zalmoxis is available on the Agency's website: ema.europa.eu/Find medicine / Human medicines / Rare disease designation
