Odiparcil is an orally administered, small molecule with the potential to become the first substrate reduction therapy in several subtypes of mucopolysacharidosis (MPS). In MPS, deficient lysosomal enzymes cause the accumulation of glycosaminoglycans (GAGs) in the lysosomes leading to the development of various serious somatic and neurologic symptoms.
Initially developed for the prevention of thrombosis after surgery, odiparcil induces the production of soluble circulating dermatan sulfate (DS) and chondroitin sulfate (CS), two GAGs inhibiting thrombus formation without causing bleeding. The same GAGs are accumulated in MPS VI and VII and either CS or DS are accumulated in MPS I, II and IVA.
ODIPARCIL IN MUCOPOLYSACHARIDOSIS TYPE VI (MPS VI)
In arylsulfatase B mutant mice, a relevant model for mucopolysacharidosis type VI (MPS VI), odiparcil showed to increase urinary GAG levels in a dose-dependent manner, in line with the mechanism described in the section above.
Source: Inventiva S.A. proprietary data
Odiparcil has received orphan drug designation for MPS VI in the USA and the EU and is currently being tested in a Phase IIa clinical trial in adult MPS VI patients, the iMProveS trial. Headline results are expected for the second half of 2019.
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PRECLINICAL IN VIVO SAFETY DATA OF ODIPARCIL
The observed pharmacological active dose of odiparcil in the animal model described in the section above corresponds to a concentration in vitro which leads to a reduction of intracellular GAG levels but not to their complete depletion. Accordingly, the observed pharmacological active dose results in an exposure that was shown to be safe in preclinical in vivo toxicology studies in mice, rats and monkeys (up to 52 weeks) and was also shown to be safe in adults during clinical studies (approx. 1800 healthy volunteers and patients exposed for up to 16 weeks).