Type of medical product:
Indications for use:
Gaucher disease Type I
Phase I clinical studies
The prevalence of this disease is 1:50 000 in the general population.
The therapeutic treatment for this disease is included in “The list of strategically important drugs, production of which must be established in the Russian Federation”.
The total estimated market demand for this type of the medical product is approximately 2.6 billion rubles.
Gaucher disease is caused by the mutant sequences of the beta-glucocerebrosidase gene, an important enzyme of phagocytic system of macrophages. The resulting genetic disorder and functional impairment of this enzyme leads to an inability of the macrophages to breakdown the complex lipid glucocerebroside. As a consequence, the macrophages are “overloaded” with glucocerebroside and are converted into so-called “Gaucher cells”. Gaucher cells are usually found in the liver, spleen, bone marrow and sometimes in the lungs, kidneys and intestines. Secondary hematologic manifestations of Gaucher disease include severe anaemia and thrombocytopenia, which are combined with the characteristic progressive hypertrophy of the spleen and liver. Bone changes are common and often the most debilitating and disabling effects of Gaucher disease.
Among other debilitating effects of this disease are:
- Osteopenia with secondary pathological fractures
- Lack of remodelling
The human recombinant beta-glucocerebrosidase which is a human lysosomal enzyme beta-glucocerebrosidase (INN-imiglucerase) is used for treatment of Gaucher’ s disease. Purified imiglucerase is a monomeric glycoprotein composed of 497 amino acids and oligosaccharide chains. Imiglucerase is expressed in the Chinese hamster ovary (CHO) cells and has one amino acid substitution compared to the wild-type enzyme (His495Arg). Once expressed, the protein is enzymatically processed in vitro by the set of glycosidases, which results in carbohydrate side chains of imiglucerase ending with mannose residues. This modification provides a longer half-life of this therapeutic protein and make it capable of entering into macrophages using the affinity to the mannose surface receptors, while the wild-type enzyme is not capable of penetrating these cells. Imiglucerase compensates for the beta-glucocerebrosidase deficiency and catalyses the hydrolysis of glucocerebroside.
At this point our domestic equivalents of imiglucerase do not exist. Imiglucerase under the trademark Cerezyme is manufactured by the pharmaceutical company Genzyme (USA) and is imported in our country to treat patients. In 2009, this drug was purchased for the amount of about 36 million U. S. dollars, which is about 60 thousand rubles for a package, containing 400 units of the medication. In 2010, imiglucerase was included among the other 57 drugs in “The list of strategically important drugs, production of which must be established in the Russian Federation”.