What is Evoltra?
Evoltra is a concentrate to prepare a solution to be administered by infusion (drip into a vein). The medicine contains the active substance called clofarabine.
What is Evoltra used for?
Evoltra is used to treat children with acute lymphoblastic leukemia (ALL), a type of lymphocyte cancer (a type of white blood cell). It is used when the disease has not responded, or when it has returned (relapse) after at least two other pharmaceutical treatments, and no other treatment is expected to produce results. Evoltra has been studied in patients under the age of 21 who have contracted the ALL for the first time.
Since the number of patients suffering from low ALL, the disease is considered rare and Evoltra was qualified as an "orphan drug" (a drug used in rare diseases) on 5 February 2002.
The medicine can only be dispensed with a prescription.
How is Evoltra used?
Treatment with Evoltra should be started and supervised by a doctor experienced in the management of patients with acute leukemia. The recommended dose is 52 mg per square meter of body surface area (calculated using the height and weight of the child). The medicine is given by infusion for a duration of two hours a day for five days. Treatment should be repeated every two to six weeks. Most patients who respond to treatment do so after one or two cycles of treatment.
How does Evoltra work?
The active substance in Evoltra, clofarabine, is a cytotoxic (a drug that kills the cells that are separating, such as cancer cells). It belongs to the group of anticancer drugs called "antimetabolites". Clofarabine is an "analogue" of adenine which is a part of the fundamental genetic material of cells (DNA and RNA). This implies that clofarabine takes the place of adenine in the body and interferes with enzymes involved in the production of genetic material called DNA polymerase and RNA reductase. This prevents the cells from producing new DNA and RNA and slows the growth of cancer cells.
How has Evoltra been studied?
The effects of Evoltra were first tested in experimental models before being studied in humans. Evoltra was studied in a study of 61 patients, under the age of 21, with ALL. All patients had already been treated with at least two types of therapies and could not take any other treatment. The average age of patients undergoing treatment was 12 years.
The main efficacy index was the number of patients who had a remission (elimination of leukemia from the bone marrow and complete or partial recovery of normal levels of the number of cells in the blood). The study did not compare Evoltra with another treatment.
What benefit has Evoltra shown during the studies?
In the main study, 20% of patients achieved remission (12 of 61). Overall, the patients who participated in the study survived for an average of 66 weeks.
After treatment with Evoltra, 10 patients were able to undergo a stem cell transplant. It is a complex operation in which the patient's bone marrow, including leukemia cells, is destroyed and replaced by cells that "recolonize" it. Stem cells are very young cells that are normally produced in the bone marrow and can develop in all the various types of blood cells.
What is the risk associated with Evoltra?
In clinical studies, the most common side effects with Evoltra (seen in more than 1 patient in 10) included neutropenia (low level of white blood cells combined with fever), anxiety, headache, flushing of the face, vomiting, diarrhea, nausea (feeling sick), itching, dermatitis (inflammation of the skin), pyrexia (fever), mucosal inflammation (inflammation of the damp membranes that cover the organs, such as those that cover the mouth internally) and fatigue (feeling tired).
For the full list of all side effects reported with Evoltra, see the Package Leaflet. Evoltra should not be used in people who may be hypersensitive (allergic) to clofarabine or any of the other ingredients. Evoltra should not be used in patients with severe kidney or liver disease. Since Evoltra is a cytotoxic drug, it should not be used during pregnancy, unless absolutely necessary; Breastfeeding should be avoided before, during and after treatment.
Why has Evoltra been approved?
Patients with ALL who have not responded or who have had a relapse after receiving at least two treatments have very little chance of surviving. The Committee for Medicinal Products for Human Use (CHMP) concluded that treatment with Evoltra may be a way to achieve a remission and facilitate a stem cell transplant. The committee decided that the benefits of Evoltra outweigh its risks for the treatment of ALL in pediatric patients who have a relapse or have not responded to at least two previous therapies and there is no other possibility of treatment that is expected to bring lasting results . The committee therefore recommended the release of the marketing authorization for Evoltra.
Evoltra has been approved in "exceptional circumstances". This means that, as the disease is rare, it has not been possible to obtain complete information on Evoltra. The European Medicines Agency (EMEA) reviews new information that may become available every year and will update this summary if necessary.
What information is still awaited for Evoltra?
The company that produces Evoltra will carry out a study to monitor the use of Evoltra in patients suffering from kidney disease and will establish a registry to monitor the side effects of the medicine.
What measures are being taken to ensure the safe use of Evoltra?
The company that produces Evotra will make sure that doctors know the best way to use Evoltra and encourage them to use the registry to monitor the side effects of the drug.
More information on Evoltra
On May 29, 2006, the European Commission issued a marketing authorization for Evoltra, valid throughout the European Union. The marketing authorization holder is Genzyme Europe BV
For a summary of the opinion of the Committee for Orphan Medicinal Products on Evoltra, click here.
For the complete version of the evaluation (EPAR) of Evoltra, click here.
Last update of this summary: 01-2009.
