Clotilia® is the world's first approved drug that utilizes the insulin receptor to cross the blood-brain barrier (BBB) and deliver the enzyme iduronate-2-sulfatase directly to the central nervous system. This represents a fundamentally new therapeutic approach for Hunter syndrome.
For a long time, the primary challenge in treating Hunter syndrome has been the lack of effective therapies for its neurological symptoms. Existing enzyme replacement therapies could only manage somatic manifestations but did not halt neurodegeneration. However, Clotilia® fundamentally changes this approach due to its innovative mechanism of action.
The molecule verenafusp alfa is a recombinant modified protein of the human lysosomal enzyme iduronate-2-sulfatase, covalently bound to the Fab fragment of a monoclonal antibody against the human insulin receptor. The Fab fragment acts as a "transporter," binding with high specificity to the insulin receptor on BBB cells. This triggers the natural process of receptor-mediated transcytosis, which "guides" the entire therapeutic molecule across the barrier. The enzyme is delivered to the brain, where it begins to break down accumulated toxic glycosaminoglycans (GAGs), stopping their pathological impact on nerve cells.
The use of the insulin receptor as a delivery target is a unique and patented technological platform.
Daniil Talyansky, CEO of GENERIUM JSC:
"This drug is a new chapter in the history of the fight against Hunter syndrome. For the first time, specialists have a tool at their disposal that radically alters the course of the disease. The drug will become available in Russia in the near future. We are convinced that our development will significantly improve the quality of life for our patients and their parents. We are also working actively to make therapy available to patients in as many countries as possible."
A multicenter, open-label, multi-cohort study of the drug's safety, pharmacokinetics, pharmacodynamics, and efficacy was conducted at 11 medical institutions with a broad cohort of patients.
Clinical trials demonstrated a statistically significant reduction in GAG levels in the cerebrospinal fluid – direct confirmation of the drug's penetration into the nervous system and its enzymatic activity. Positive dynamics were observed according to a number of neuropsychological tests, indicating a beneficial effect on the cognitive sphere. Stabilization and improvement in respiratory function, joint mobility, and other physical parameters were noted.
This therapeutic method opens new possibilities for combating neurocognitive impairments in patients with Hunter syndrome. The drug will be manufactured by GENERIUM in Russia on a full-cycle basis.