Drug Overview
Crestor (rosuvastatin calcium; AstraZeneca/AbbVie/Shionogi) is a member of the statin class of antidyslipidemic drugs, which competitively inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG Co-A) reductase. HMG Co-A reductase is a rate-limiting enzyme that converts HMG Co-A to mevalonate in the mevalonate pathway. This hepatic pathway is responsible for synthesizing various molecules, including cholesterol. The binding of Crestor at the active site not only prevents substrate binding but also alters the enzyme’s conformation, preventing the attainment of a functional structure. The reduction in de novo cholesterol synthesis results in upregulation of low-density lipoprotein (LDL) receptors on hepatocytes, consequently increasing LDL endocytosis. Crestor is also effective at treating homozygous familial hypercholesterolemia, despite the fact that LDL receptors are non-functional in patients with this disease. This is explained by Crestor’s ability to limit cholesterol availability for the hepatic synthesis of lipoproteins containing apolipoprotein B, such as LDL.
With a generic version of Crestor now available in the US, the drug’s revenue is expected to continue to plummet as physicians opt for cheaper, generic rosuvastatin. Crestor lost market exclusivity in May 2016, and Allergan launched the first generic version of the drug 67 days before the end of its pediatric exclusivity period. As one of the last major statins to retain market exclusivity, Crestor has generated significant revenues in the dyslipidemia market over the past decade. Crestor’s high uptake in this indication has been boosted by head-to-head trials against key competitors and various label expansions. Following Crestor’s loss of market exclusivity, AstraZeneca may look to partner with other pharmaceutical companies and produce fixed-dose combinations of Crestor and other antidyslipidemics in an effort to mitigate the expected drop in revenue.
Crestor (rosuvastatin calcium; AstraZeneca/AbbVie/Shionogi) is a member of the statin class of antidyslipidemic drugs, which competitively inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG Co-A) reductase. HMG Co-A reductase is a rate-limiting enzyme that converts HMG Co-A to mevalonate in the mevalonate pathway. This hepatic pathway is responsible for synthesizing various molecules, including cholesterol. The binding of Crestor at the active site not only prevents substrate binding but also alters the enzyme’s conformation, preventing the attainment of a functional structure. The reduction in de novo cholesterol synthesis results in upregulation of low-density lipoprotein (LDL) receptors on hepatocytes, consequently increasing LDL endocytosis. Crestor is also effective at treating homozygous familial hypercholesterolemia, despite the fact that LDL receptors are non-functional in patients with this disease. This is explained by Crestor’s ability to limit cholesterol availability for the hepatic synthesis of lipoproteins containing apolipoprotein B, such as LDL.
With a generic version of Crestor now available in the US, the drug’s revenue is expected to continue to plummet as physicians opt for cheaper, generic rosuvastatin. Crestor lost market exclusivity in May 2016, and Allergan launched the first generic version of the drug 67 days before the end of its pediatric exclusivity period. As one of the last major statins to retain market exclusivity, Crestor has generated significant revenues in the dyslipidemia market over the past decade. Crestor’s high uptake in this indication has been boosted by head-to-head trials against key competitors and various label expansions. Following Crestor’s loss of market exclusivity, AstraZeneca may look to partner with other pharmaceutical companies and produce fixed-dose combinations of Crestor and other antidyslipidemics in an effort to mitigate the expected drop in revenue.
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