What is Zavesca?
Zavesca is a medicine that contains the active substance miglustat, available as white 100 mg capsules.
What is Zavesca used for?
Zavesca is indicated to treat two rare inherited diseases that affect the way the body metabolizes fat. Both diseases cause fatty substances (called glucosphingolipids) to accumulate in the body. Zavesca is used in the following cases:
- adults with type 1 Gaucher disease in its mild to moderate forms. Suffering patients lack an enzyme (glucocerebrosidase); this deficiency determines the accumulation of a type of glycosphingolipids (called glucosylceramide) in various parts of the body, eg. spleen, liver, bones. Zavesca is used in patients not suitable for treatment with standard enzyme replacement therapy (ERT) by infusion (drip into a vein);
- adults, adolescents and children with Niemann-Pick type C disease, a disease that can lead to death, in which an accumulation of glycosphingolipids occurs in cells within the brain and in other parts of the body. Zavesca is used for the treatment of "neurological" symptoms of the disease (symptoms concerning the brain and nerves). These symptoms include: loss of coordination, problems resulting from "saccadic" (rapid) eye movements that can damage eyesight, developmental delay, difficulty in swallowing, increased muscle tone, convulsions and learning difficulties.
As the number of patients suffering from these diseases is low, they are considered "rare" and therefore Zavesca received the designation of "orphan medicine" respectively on 18 October 2000, as regards type 1 Gaucher disease, and 16 February 2006, for Niemann-Pick type C disease.
The medicine can only be obtained with a prescription.
How is Zavesca used?
Treatment with Zavesca should be started and monitored by physicians experienced in the management of Gaucher disease or Niemann-Pick type C disease.
The recommended starting dose for treating patients with type 1 Gaucher disease is one capsule administered orally, three times a day. Regarding Niemann-Pick type C disease, the recommended dose is two capsules, three times a day, for adult and adolescent patients. There
dose varies according to weight and height for children under 12 years of age. Zavesca can be taken on a full or fasting stomach. Zavesca is a long-term therapy medicine.
The dose should be reduced in patients with kidney problems and, at least temporarily, in patients who develop diarrhea. Studies of the medicine have not been conducted in patients with liver problems. For more information, see the Summary of Product Characteristics (included in the EPAR).
How does Zavesca work?
The active substance in Zavesca, miglustat, inhibits the action of an enzyme, called glucosylceramide synthase. This enzyme is part of the first phase of glycosphingolipid production. By preventing the action of the enzyme, miglustat can reduce the production of glycosphingolipids in cells. This should slow or prevent the symptoms of type 1 Gaucher disease and reduce the symptoms of Niemann-Pick type C disease.
What studies have been carried out on Zavesca?
The efficacy of Zavesca in the treatment of mild to moderate type 1 Gaucher disease was the subject of a main study involving 28 patients who could not or did not want to undergo enzyme replacement therapy. The main part of the study lasted one year; 13 of the patients continued to take the medicine for another two years. The study aimed to measure the effect of Zavesca on the volume of the liver and spleen and to determine whether it had effects on blood values, such as concentration of hemoglobin (a protein found in red blood cells that carries oxygen in the body) and platelet counts (components that participate in blood clotting).
Regarding Niemann-Pick type C disease, the efficacy of Zavesca was studied in a main study involving 31 patients, of which 12 were less than 12 years old. The study compared the effects of Zavesca in combination with standard therapy (measures used to relieve symptoms) and standard therapy alone. The main efficacy index was the change in patients of the frequency of horizontal saccadic eye movements after one year; the study also examined other neurological symptoms including the patient's ability to swallow and their intellectual functions. Some patients remained in treatment for up to five and a half years. a survey was also conducted on 66 patients treated with Zavesca.
What benefit has Zavesca shown during the studies?
In the study related to type 1 Gaucher disease, a decrease in liver volume of 12% and spleen volume of 19% was found after one year. An average increase in hemoglobin concentration of 0.26 g per deciliter was also detected, as well as an increase in the platelet count of 8.29 million per milliliter. The beneficial effects of Zavesca have remained unchanged over three years of continuous treatment.
In the study of Niemann-Pick type C disease, improvement in eye movements was similar in patients treated with and without Zavesca. However, signs of improvement in swallowing ability and intellectual function were found in patients treated with Zavesca. The investigation showed that the medicine made the worsening of symptoms stable or reduced for about three quarters of the patients.
What is the risk associated with Zavesca?
The most frequent side effects associated with Zavesca (seen in more than 1 patient in 10) are weight loss, tremor, diarrhea, flatulence and abdominal pain (stomach ache). For the full list of all side effects reported with Zavesca, see the Package Leaflet.
Zavesca should not be used in patients who may be hypersensitive (allergic) to miglustat or any of the other ingredients.
Why has Zavesca been approved?
The Committee for Medicinal Products for Human Use (CHMP) decided that the benefits shown by Zavesca outweigh the risks regarding the treatment, by the oral route, of mild or moderate type 1 Gaucher disease in unsuitable adult patients to be treated with enzyme replacement therapy (ERT) and progressive neurologic manifestations in adult and pediatric patients with Niemann-Pick type C disease. The committee therefore recommended the granting of a marketing authorization for Zavesca.
Zavesca was authorized "in exceptional circumstances" because, being a rare disease, it was not possible to obtain complete data on the medicine. The European Medicines Agency (EMEA) will proceed every year to examine any new data that has become available in the meantime, updating this summary if necessary.
What information is still awaited for Zavesca?
The manufacturer of Zavesca has undertaken to carry out the following studies on the efficacy and safety of the product with regard to type 1 Gaucher disease:
- a program following the marketing of the product to inform doctors about the use of Zavesca and to ensure that patients report the safety aspects of the medicine;
- a follow-up study on patients already involved in clinical tests, to continue the evaluation of the safety and efficacy of the medicine as well as to have greater feedback about the neurological aspects of the disease;
- a study on the efficacy and safety of Zavesca in patients who switch to Zavesca after enzyme replacement therapy;
- a further study on the natural history of the disease, conducted jointly with the European working group on Gaucher disease (EWGGD).
More information on Zavesca:
On November 20, 2002, the European Commission issued a marketing authorization for Zavesca to Actelion Registration Ltd, valid throughout the European Union. The marketing authorization was renewed on 20 November 2007.
For the registration of the status of orphan drug of Zavesca click here (for type 1 Gaucher disease) and here (for Niemann-Pick type C disease).
For the full EPAR for Zavesca, click here.
Last update of this summary: 01-2009
