CRED Understanding Clinical Development 2024

TOPRA CRED Understanding Clinical Development Case Study Devostatin

Part I (Phases 1 and 2) There are a number of different drugs for the treatment of hypercholesterolaemia and prevention of cardiovascular disease. One of the main treatments is the group belonging to the “statins” family. These include rosuvastatin (Crestor), pravastatin (Lipostat), fluvastatin (Lescol), atorvastatin (Lipitor) to name but a few. For hypercholesterolaemia, they are indicated as an adjunct to diet for the reduction of elevated total cholesterol (total-C), LDL-cholesterol (LDL-C), apolipoprotein B, and triglycerides in adults, adolescents and children aged 10 years or older with primary hypercholesterolaemia including familial hypercholesterolaemia (heterozygous variant) or combined (mixed) hyperlipidaemia (corresponding to Types IIa and IIb of the Fredrickson classification) when response to diet and other nonpharmacological measures is inadequate. They also indicated to reduce total-C and LDL-C in adults with homozygous familial hypercholesterolaemia as an adjunct to other lipid-lowering treatments (e.g. LDL apheresis) or if such treatments are unavailable. Due to the increase of childhood obesity these treatments are increasingly being administered to a younger population. For prevention of cardiovascular disease, statins are indicated for the prevention of cardiovascular events in adult patients estimated to have a high risk for a first cardiovascular event as an adjunct to correction of other risk factors. One of the rare but important side-effects of statins is their effect on skeletal muscle such as myalgia, myopathy and rarely rhabdomyolysis (a breakdown of the muscle). Also there may be an elevation of creatinine kinase levels. Other effects are proteinuria which is found to decrease or disappear spontaneously on continued therapy. Effects on the liver have also been identified with rises in the levels of serum transaminases.Statins act as an inhibitor of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase which is an enzyme that catalyses the early rate-limiting steps in the biosynthesis of cholesterol. Statins appear to be well tolerated by the vast majority of the population and are considered essential to help in the treatment of hypercholesterolaemia and mixed dyslipidaemia. Summary of Data Available Devostatin is now being developed for the treatment of hypercholesterolaemia and prevention of cardiovascular disease. It is thought that its safety profile will be better compared to the commercially available products as the effective dose should be much lower. A comprehensive preclinical development programme has been performed. Data that have been generated include:

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