Crestor - Informa · expected to continue to plummet as physicians opt for cheaper, generic rosuvastatin. Crestor lost market exclusivity in May 2016, and Allergan launched the first

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CrestorProduct Analysis

Ref Code: DMKC0145153Author: Louisa Joseph

Product Analysis : Crestor 2

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Published on 06 October 2017



CONTENTS

LIST OF FIGURES

LIST OF TABLES

4 PRODUCT PROFILES

4 Crestor : Dyslipidemia

8 Figure 1: Crestor for dyslipidemia – SWOT analysis

9 Figure 2: Datamonitor Healthcare's drug assessment summary of Crestor for dyslipidemia

10 Figure 3: Datamonitor Healthcare’s drug assessment summary of Crestor for dyslipidemia

12 Figure 4: Crestor sales forecast for dyslipidemia in the US, Japan, and five major EU markets, by country, 2016–25

5 Table 1: Crestor drug profile

7 Table 2: Crestor pivotal trial data in dyslipidemia

13 Table 3: Crestor sales for dyslipidemia in the US, Japan, and five major EU markets, by country ($m), 2016–25




Product Profiles Crestor : Dyslipidemia PRODUCT PROFILE

ANALYST OUTLOOK With a generic version of Crestor (rosuvastatin calcium; AstraZeneca/AbbVie/Shionogi) now available in the US, the drug’s revenue isexpected to continue to plummet as physicians opt for cheaper, generic rosuvastatin. Crestor lost market exclusivity in May 2016, andAllergan launched the first generic version of the drug 67 days before the end of its pediatric exclusivity period. As one of the lastmajor 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 producefixed-dose combinations (FDCs) of Crestor and other antidyslipidemics in an effort to mitigate the expected drop in revenue.

DRUG OVERVIEW Crestor is a member of the statin class of antidyslipidemic drugs, which competitively inhibit 3-hydroxy-3-methylglutaryl-co-enzyme A(HMG Co-A) reductase. HMG Co-A reductase is a rate-limiting enzyme that converts HMG Co-A to mevalonate in the mevalonatepathway. This hepatic pathway is responsible for synthesizing various molecules, including cholesterol. The binding of Crestor at theactive site not only prevents substrate binding but also alters the enzyme’s conformation, preventing the attainment of a functionalstructure. The reduction in de novo cholesterol synthesis results in upregulation of low-density lipoprotein (LDL) receptors onhepatocytes, consequently increasing LDL endocytosis. Crestor is also effective at treating homozygous familial hypercholesterolemia(FH), despite the fact that LDL receptors are non-functional in patients with this disease. This is explained by Crestor’s ability to limitcholesterol availability for the hepatic synthesis of lipoproteins containing apolipoprotein B, such as LDL (Stancu and Sima, 2001).




DEVELOPMENT OVERVIEW Crestor was approved for the treatment of primary hypercholesterolemia and mixed dyslipidemia in the EU through the mutualrecognition procedure in November 2002. The Netherlands acted as the reference member state and the successful outcomeresulted in subsequent approvals in the UK, France, and Italy (Biomedtracker, 2017). Crestor also gained approval in the US in 2003for the treatment of various lipid disorders (AstraZeneca press release, 2003). Japanese approval was received in January 2005following a lengthy regulatory process. This was contingent on a post-marketing surveillance program to confirm the drug’s safety andefficacy in the local population (AstraZeneca press release, 2005).

Table 1: Crestor drug profile

Molecule rosuvastatin calcium

Mechanism of action HMG Co-A reductase inhibitor

Originator Shionogi

Marketing company AstraZeneca (US, Japan, 5EU), AbbVie (US), Shionogi (Japan)

Approved indication Dyslipidemia

Contraindications Hypersensitivity, active liver disease, pregnancy, nursing mothers

Formulation Oral tablet

Dosing frequency 5–40mg once daily

First approval date for dyslipidemia November 2002 (5EU), August 2003 (US), January 2005 (Japan)

Primary patent expiry Q3 2016 (US), Q4 2017 (5EU), Q2 2017 (Japan)

Geographic availability US, 5EU, Japan

Alternative names S4522, ZD4522

2016 global total brand sales $3,798m

5EU = five major EU markets (France, Germany, Italy, Spain, and the UK); HMG Co-A = 3-hydroxy-3-methylglutaryl-co-enzyme A

Source: Biomedtracker; Medtrack; Pharmaprojects; Crestor prescribing information, 2016




The table below summarizes the pivotal trial data leading to the regulatory approval of Crestor in dyslipidemia.



Table 2: Crestor pivotal trial data in dyslipidemia

Trial Sample size Target patients Dosing tested and duration Results Reference

STELLAR(NCT00654537)(Phase IIIb)

2,431 Primaryhypercholesterolemia

Once-daily dosing for six weeks of either Crestor (10mg,20mg, or 40mg), Lipitor (10mg, 20mg, 40mg, or 80mg),Zocor (10mg, 20mg, 40mg, or 80mg), or Pravachol(10mg, 20mg, or 40mg)

Percentage of patients to achieve LDL-Clevels of <100mg/dL:Crestor = 53–80%Lipitor = 18–70%Zocor = 8–53%Pravachol = 1–8%

Crestor prescribinginformation, 2016;McKenney et al., 2003

Phase III 374 Hypercholesterolemic patients

Once-daily Crestor (5mg, 10mg, 20mg, 40mg, or 80mg)or Lipitor (10mg, 20mg, 40mg, or 80mg) for six weeks

Percentage decrease in LDL-C:Crestor = 47–62%Lipitor = 38–54%

Schneck et al., 2003

Phase III 623 HeFH 20mg/day of Lipitor or Crestor with forced titration atsix-week intervals to 80mg/day18-week study duration

Crestor versus Lipitor:LDL-C = -58% versus -50%HDL-C = 12% versus 3%

Stein et al., 2003

Phase III 40 HoFH Crestor 20mg titrated to 40mg at a six-week interval Mean LDL-C reduction from baseline = 22% Crestor prescribinginformation, 2016

HDL-C = high-density lipoprotein cholesterol; HeFH = heterozygous familial hypercholesterolemia; HoFH = homozygous familial hypercholesterolemia; LDL-C = low-density lipoprotein cholesterol

Source: various (see above)




SWOT ANALYSIS

CLINICAL AND COMMERCIAL ATTRACTIVENESS The figure below depicts Datamonitor Healthcare’s drug assessment summary for Crestor in dyslipidemia.

Figure 1: Crestor for dyslipidemia – SWOT analysis

Source: Datamonitor Healthcare




The figure below provides a breakdown of how Datamonitor Healthcare scored Crestor’s clinical and commercial attractiveness. Theweighting given to each attribute is also shown.

Figure 2: Datamonitor Healthcare's drug assessment summary of Crestor for dyslipidemia





PATIENT BASED FORECAST

FORECAST ASSUMPTIONS Datamonitor Healthcare makes the fol lowing assumptions in i ts forecast of Crestor (rosuvastat in calc ium;AstraZeneca/AbbVie/Shionogi ) for dysl ipidemia: Regulatory - Crestor was approved for the treatment of primary hypercholesterolemia and mixed dyslipidemia in the EU, US, and Japan in Q42002, Q3 2003, and Q2 2005, respectively. - Generic atorvastatin entered the US market in Q2 2016 and the European markets in Q2 2017. Generics are expected to enter theJapanese market in Q4 2017. Competition - Prior to launch of rosuvastatin generics, Crestor dominated the statin market on account of its superior efficacy and because it wasthe last major statin to lose market exclusivity.

Figure 3: Datamonitor Healthcare’s drug assessment summary of Crestor for dyslipidemia





- Crestor’s revenues will face a steep decline due to competition from marketed generic alternatives. With three generic alternativesnow available, Crestor revenues are expected to decline in a similar manner to Lipitor (atorvastatin calcium;Pfizer/Astellas/Menarini/Almirall). Lipitor experienced a decrease in sales from $11,940m in 2010 to $4,863m in 2012, following itspatent expiry in 2011, and a similar decline is expected for Crestor’s branded revenue (Medtrack, 2017). - Datamonitor Healthcare forecasts that the recently launched proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors will beadded to a small percentage of Crestor’s treatment regimens. Initial use of the PCSK9 inhibitors is expected to be restricted to thetreatment of familial hypercholesterolemia and secondary-prevention patients who are unable to reach low-density lipoproteincholesterol goals on maximally tolerated statin therapy. Dosing - Datamonitor Healthcare assumes a 10mg once daily dosing regimen for Crestor in the US, Japan and five major EU markets. Pricing Please view the accompanying datapack for a full table of drug costs per patient per year.

CRESTOR FORECAST, 2016–25 The figure and table below show Datamonitor Healthcare’s forecast of Crestor in dyslipidemia, by country, over 2016–25.




Figure 4: Crestor sales forecast for dyslipidemia in the US, Japan, and five major EU markets, by country, 2016–25




Table 3: Crestor sales for dyslipidemia in the US, Japan, and five major EU markets, by country ($m), 2016–25

Country 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025

US 1,222 732 687 641 611 587 578 577 575 574

Japan 521 189 163 141 127 117 109 102 97 96

France 170 138 46 33 28 25 22 21 21 21

Germany 53 44 14 10 9 8 7 7 6 6

Italy 66 63 21 15 13 11 10 9 9 9

Spain 185 176 58 41 35 31 28 27 27 26

UK 117 112 37 27 23 20 18 17 17 17

Grand total 2,334 1,455 1,026 908 845 798 771 760 753 750

Note: totals may not sum due to rounding.





BIBLIOGRAPHY AstraZeneca press release (2003) Crestor® Receives FDA Approval. Available from: https://newswise.com/articles/astrazenecas-crestor-rosuvastatin-calcium-receives-fda-approval [Accessed 14 August 2017]. AstraZeneca press release (2005) Council Recommends Approval of Crestor in Japan. Available from: http://www.biospace.com/News/1-release-council-recommends-approval-of-crestor/18536020 [Accessed 14 August 2017]. Crestor prescribing information (2016) Crestor prescribing information. Available from:https://www.azpicentral.com/crestor/crestor.pdf#page=1 [Accessed 14 August 2017]. McKenney JM, Jones PH, Adamczyk MA, Cain VA, Bryzinski BS, et al. (2003) Comparison of the efficacy of rosuvastatin versusatorvastatin, simvastatin, and pravastatin in achieving lipid goals: results from the STELLAR trial. Current Medical Research andOpinion, 19(8), 689–98. Schneck DW, Knopp RH, Ballantyne CM, McPherson R, Chitra RR, et al. (2003) Comparative effects of rosuvastatin and atorvastatinacross their dose ranges in patients with hypercholesterolemia and without active arterial disease. The American Journal ofCardiology, 91(1), 33–41. Stancu C, Sima A (2001) Statins: mechanism of action and effects. Journal of Cellular and Molecular Medicine, 5(4), 378–87. Stein EA, Strutt K, Southworth H, Diggle PJ, Miller E (2003) Comparison of rosuvastatin versus atorvastatin in patients withheterozygous familial hypercholesterolemia. The American Journal of Cardiology, 92(11), 1287–93.


https://newswise.com/articles/astrazenecas-crestor-rosuvastatin-calcium-receives-fda-approval

https://newswise.com/articles/astrazenecas-crestor-rosuvastatin-calcium-receives-fda-approval

http://www.biospace.com/News/1-release-council-recommends-approval-of-crestor/18536020

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Crestor - Informa · expected to continue to plummet as physicians opt for cheaper, generic rosuvastatin. Crestor lost market exclusivity in May 2016, and Allergan launched the first