NICE Recommends Astellas’ EVRENZO▼™ (roxadustat) For Adults With Symptomatic Anaemia Associated With Chronic Kidney Disease

NICE Recommends Astellas’ EVRENZO▼™ (roxadustat) For Adults With Symptomatic Anaemia Associated With Chronic Kidney Disease

 

• EVRENZO^TM (roxadustat) is the first hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor to be recommended by NICE¹
• Over 75,000 adults in England and Wales living with anaemia associated with chronic kidney disease (CKD) could have access to roxadustat through the NHS^{1, 2}
• Anaemia associated with CKD can have a large impact on people’s lives. In a survey of people with anaemia associated with CKD:³

• 41% report not being able to look after their family
• 46% report not being able to exercise as they would like
• 44% report having to stop work indefinitely due to the condition

United Kingdom, 9, June, 2022 – Astellas Pharma Ltd. (part of the Astellas Pharma Inc group TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., “Astellas”) is pleased to announce that the National Institute for Health and Care Excellence (NICE) has recommended EVRENZO™ (roxadustat), as an option for treating symptomatic anaemia associated with chronic kidney disease (CKD) in adults with stage 3 to 5 CKD with no iron deficiency and are not on dialysis at the start of treatment.^{1, 4, 5}

 

The recommendation, in line with the marketing authorisation for roxadustat, means roxadustat will be available as an alternative to erythropoietin stimulating agents (ESAs) for patients who are not on dialysis at the time of starting treatment (with no requirement to stop should they start dialysis).^1,4,5

 

Anaemia is a common complication of CKD.² While many will experience mild symptoms, it can be severely debilitating and can have a profound impact on quality of life.⁶ If untreated, people with severe anaemia associated CKD have increased cardiovascular (CV) risk and higher levels of mortality than people with CKD alone.^{7, 8} The current treatment of symptomatic anaemia associated with CKD for many has involved injections of recombinant erythropoetin (the hormone that stimulates production of red blood cells) and infusions of supplementary iron.⁹

 

Through a mechanism of action that mimics the body’s natural response to low-oxygen levels, roxadustat stimulates the increase of red blood cell production and improves utilsation of iron stores via an oral tablet.¹⁰

 

‘Most people do not realise the impact anaemia can have on a person’s life’ said Andrea Brown, Chief Executive, National Kidney Federation, UK. ‘A new treatment is important for those who do not tolerate current therapies and as a means of simplifying treatment for thousands of adults with anaemia assocaited with CKD.’

 

The final appraisal document was based on results from a pivotal Phase 3 clinical study (DOLOMITES), a radomised open-label, active controlled study, comparing roxadustat to an ESA (darbepoetin-alfa) in non-dialysis dependent CKD patients with anaemia.¹¹ The results of this study support roxadustat as efficacious in achieving and maintaining target haemoglobin (Hb) levels (10–12 g/dL), comparable with ESA, with reduced use of intravenous (IV) iron in non-dialysis dependent patients.^11-18

 

‘NICE’s decision is a vote of confidence in roxadustat as a cost-effective oral treatment option,’ said Dr Timir Patel, Medical Director, Astellas UK & Ireland. ‘The clinical trial programme demonstrates the sustained effect of roxadustat in increasing haemoglobin levels and with a reduced requirement for intravenous iron in adults with anaemia associated with CKD. We will work with the NHS to ensure this treatment fits optimally into a patient’s ongoing care, with the intent of improving the lives of adults with symptomatic anaemia associated with CKD.’

 

The safety profile of roxadustat has been demonstrated through the ALPINE clinical trial programme, where roxadustat was overall comparable to ESAs for the majority of safety variables evaluated and is reflective of the adult CKD populations studied.^{4, 5, 11-18}  

For more information on roxadustat, please email medinfo.gb@astellas.com.

 

About CKD and Anaemia associated with CKD
Chronic kidney disease (CKD) is a progressive disease characterised by gradual loss of kidney function that may eventually lead to kidney failure or end stage renal disease, requiring dialysis or kidney transplant.¹⁹ Many patients with CKD die of cardiovascular complications before progressing to kidney failure and as such the prevalence of early kidney disease is much greater than end stage disease.^{20, 21} CKD is a highly prevalent disease affecting approximately one in 10 people globally²² and is projected to become the fifth most common cause of premature death globally by 2040.²³

 

Anaemia, a serious medical condition, in which patients have insufficient red blood cells and low levels of haemoglobin.²⁴ It is a common early complication of CKD affecting approximately 20% of CKD patients, according to UK data.²⁵ Anaemia associated with CKD is associated with an increased risk of hospitalisation, cardiovascular complications and worsening kidney function.^{6, 26} The condition can also cause significant fatigue, cognitive dysfunction and reduced quality of life.^{6, 27-29} Current management includes the use iron supplements and erythropoietin stimulating agents (ESAs). Less frequently, blood transfusions are used for treating severe anaemia, however, they may reduce a patient’s opportunity for kidney transplant and can increase the risk of infection and/or complications such as heart failure and allergic reactions.^30-33

 

About Roxadustat
Roxadustat, an oral medicine, is the first in a new class of medicines, HIF-PH inhibitors, that promote erythropoiesis, or red blood cell production, through increased endogenous production of erythropoietin; improved iron absorption and mobilisation; and downregulation of hepcidin. Roxadustat is also in Phase 3 clinical development for anaemia associated with myelodysplastic syndromes (MDS) and Phase 2 for chemotherapy-induced anaemia (CIA).

 

Roxadustat is approved in the United Kingdom, EU member states, including the EEA countries, as well as in Japan, China, Chile and South Korea for the treatment of anaemia associated with CKD in adult patients on dialysis (DD) and not on dialysis (NDD). Several other licensing applications for roxadustat have been submitted by Astellas and AstraZeneca to regulatory authorities across the globe and are currently in review.

 

Astellas and FibroGen are collaborating on the development and commercialization of roxadustat for the potential treatment of anaemia associated with CKD in territories including Japan, Europe, Turkey, Russia and the Commonwealth of Independent States, the Middle East, and South Africa. FibroGen and AstraZeneca are collaborating on the development and commercialization of roxadustat for the potential treatment of anaemia associated with CKD in the U.S., China, other markets in the Americas, in Australia/New Zealand, and Southeast Asia.

 

Important Safety Information

The full European Summary of Product Characteristics (SPC/SmPC) for roxadustat is available from the Electronic Medicines Compendium UK: www.medicines.org.uk and for Northern Ireland at www.ema.europa.eu ²

 

About Astellas

Astellas Pharma Inc., is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into value for patients. For more information, please visit our website at https://www.astellas.com/en.

 

Astellas Cautionary Notes
In this press release, statements made with respect to current plans, estimates, strategies and beliefs, and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets and (vi) infringements of Astellas' intellectual property rights by third parties.

 

Information about pharmaceutical products (including products currently in development) that is included in this press release is not intended to constitute an advertisement or medical advice.

 

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References (email)

1. PLACEHOLDER - NICE guidance. Final Appraisal Document (FAD) Roxadustat. January 2022.  

2. EMC Northern Ireland. EVRENZO (roxadustat) Summary of Product Characteristics., https://www.emcmedicines.com/en-gb/northernireland/medicine?id=ad75eea6-ef06-4213-9929-ab5417f0af9a&type=smpc (accessed May 2022). 

3. EMC Great Britain. EVRENZO (roxadustat) Summary of Product Characteristics, https://www.medicines.org.uk/emc/product/12835/pil#gref (accessed May 2022). 

4. The Nobel Prize. The Nobel Prize in Physiology or Medicine 2019 https://www.nobelprize.org/prizes/medicine/2019/press-release/ (accessed May 2022). 

5. Babitt JL and Lin HY. Mechanisms of anemia in CKD. J Am Soc Nephrol 2012; 23: 1631-1634. 2012/09/01. DOI: 10.1681/asn.2011111078. 

6. Astellas. Data on File. 2022. 

7. Eriksson D, Goldsmith D, Teitsson S, et al. Cross-sectional survey in CKD patients across Europe describing the association between quality of life and anaemia. BMC Nephrol 2016; 17: 97. 2016/07/28. DOI: 10.1186/s12882-016-0312-9. 

8. Brooks et al.. Anaemia of Chronic Kidney Disease. The Renal Association Clinical Practice Guideline 2017. 

9. Besarab A, Chernyavskaya E, Motylev I, et al. Roxadustat (FG-4592): Correction of Anemia in Incident Dialysis Patients. J Am Soc Nephrol 2016; 27: 1225-1233. 2015/10/24. DOI: 10.1681/asn.2015030241. 

10. Gupta N and Wish JB. Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors: A Potential New Treatment for Anemia in Patients With CKD. Am J Kidney Dis 2017; 69: 815-826. 2017/03/01. DOI: 10.1053/j.ajkd.2016.12.011. 

11. Haase VH. HIF-prolyl hydroxylases as therapeutic targets in erythropoiesis and iron metabolism. Hemodial Int 2017; 21 Suppl 1: S110-s124. 2017/04/28. DOI: 10.1111/hdi.12567. 

 

References (press release)

1. NICE guidance. Final Appraisal Documnet (FAD) Roxadustat. June 2022.

2. Astellas Pharma Inc. Data on file.

3. Partnerships R. Data on File. Research Partnerships re. anaemia associated with CKD. PR Market Research. NEPH_2020_0145_APE 2020.

4. EMC. Evrenzo (roxadustat) film coated tablets, https://www.medicines.org.uk/emc/product/12835/pil#gref. (Last accessed June 2022).

5. EMC Northern Ireland. EVRENZO Summary of Product Characteristics, https://www.emcmedicines.com/en-gb/northernireland/medicine?id=ad75eea6-ef06-4213-9929-ab5417f0af9a&type=smpc (Last accessed June 2022).

6. Eriksson D, Goldsmith D, Teitsson S, et al. Cross-sectional survey in CKD patients across Europe describing the association between quality of life and anaemia. BMC Nephrol 2016; 17: 97. 2016/07/28. DOI: 10.1186/s12882-016-0312-9.

7. Astor BC, Coresh J, Heiss G, et al. Kidney function and anemia as risk factors for coronary heart disease and mortality: the Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J 2006; 151: 492-500. 2006/01/31. DOI: 10.1016/j.ahj.2005.03.055.

8. Mohanram A, Zhang Z, Shahinfar S, et al. Anemia and end-stage renal disease in patients with type 2 diabetes and nephropathy. Kidney Int 2004; 66: 1131-1138. 2004/08/26. DOI: 10.1111/j.1523-1755.2004.00863.x.

9. Brooks. Anaemia of Chronic Kidney Disease. The Renal Association Clinical Practice Guideline 2017.

10. Koury MJ and Haase VH. Anaemia in kidney disease: harnessing hypoxia responses for therapy. Nat Rev Nephrol 2015; 11: 394-410. 2015/06/10. DOI: 10.1038/nrneph.2015.82.

11. Barratt J, Andric B, Tataradze A, et al. Roxadustat for the treatment of anaemia in chronic kidney disease patients not on dialysis: a phase 3, randomised, open-label, active-controlled study (DOLOMITES). Nephrol Dial Transplant 2021 2021/06/03. DOI: 10.1093/ndt/gfab191.

12. Csiky B, Schömig, M., Esposito, C. et al. Roxadustat for the Maintenance Treatment of Anemia in Patients with End-Stage Kidney Disease on Stable Dialysis: A European Phase 3, Randomized, Open-Label, Active-Controlled Study (PYRENEES). Adv Ther (2021) 2021. DOI: https://doi.org/10.1007/s12325-021-01904-6.

13. Provenzano R, Shutov E, Eremeeva L, et al. Roxadustat for anemia in patients with end-stage renal disease incident to dialysis. Nephrol Dial Transplant 2021 2021/02/26. DOI: 10.1093/ndt/gfab051.

14. Charytan C EM, Leong R, et al,. SIERRAS: A phase 3, open-label, randomized, active-controlled study of the efficacy and safety of roxadustat in the maintenance treatment of anemia in subjects with ESRD on stable dialysis.

15. Fishbane S GN, Pergola PE,. ROCKIES: An international phase 3, randomized, open-label, active-controlled study of roxadustat for anemia in dialysis-dependent CKD patients. Presented at the American Society of Nephrology (ASN) Annual Meeting; 5–10 November 2019; Washington, DC Oral TH-OR022.

16. Shutov E, Sułowicz W, Esposito C, et al. Roxadustat for the treatment of anemia in chronic kidney disease patients not on dialysis: a phase 3, randomized, double-blind, placebo-controlled study (ALPS). Nephrol Dial Transplant 2021 2021/02/26. DOI: 10.1093/ndt/gfab057.

17. Coyne DW, Roger SD, Shin SK, et al. Roxadustat for CKD-related Anemia in Non-dialysis Patients. Kidney Int Rep 2021; 6: 624-635. 2021/03/19. DOI: 10.1016/j.ekir.2020.11.034.

18. Fishbane S, El-Shahawy MA, Pecoits-Filho R, et al. Roxadustat for Treating Anemia in Patients with CKD Not on Dialysis: Results from a Randomized Phase 3 Study. J Am Soc Nephrol 2021; 32: 737-755. 2021/02/12. DOI: 10.1681/asn.2020081150.

19. Mayo Clinic. Chronic kidney disease, https://www.mayoclinic.org/diseases-conditions/chronic-kidney-disease/symptoms-causes/syc-20354521 (Last accessed June 2022).

Astellas Data on File. Iron usage in patients not on dialysis treated with either roxadustat or ESA (DOLOMITES)

20. Ojo A. Addressing the global burden of chronic kidney disease through clinical and translational research. Trans Am Clin Climatol Assoc 2014; 125: 229-243; discussion 243-226. 2014/08/16.

21. Subbiah AK, Chhabra YK and Mahajan S. Cardiovascular disease in patients with chronic kidney disease: a neglected subgroup. Heart Asia 2016; 8: 56-61. 2016/12/10. DOI: 10.1136/heartasia-2016-010809.

22. Nephrology ISo. Chronic kidney disease. Global kidney health atlas, https://www.theisn.org/wp-content/uploads/2021/05/GKHAtlas_2019_WebFIle-1.pdf (2019).

23. Foreman KJ, Marquez N, Dolgert A, et al. Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016-40 for 195 countries and territories. Lancet 2018; 392: 2052-2090. 2018/10/21. DOI: 10.1016/S0140-6736(18)31694-5.

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25. Dmitrieva O, de Lusignan S, Macdougall IC, et al. Association of anaemia in primary care patients with chronic kidney disease: cross sectional study of quality improvement in chronic kidney disease (QICKD) trial data. BMC Nephrol 2013; 14: 24. 2013/01/29. DOI: 10.1186/1471-2369-14-24.

26. Pulignano G, Del Sindaco D, Di Lenarda A, et al. Chronic renal dysfunction and anaemia are associated with cognitive impairment in older patients with heart failure. J Cardiovasc Med (Hagerstown) 2014; 15: 481-490. 2014/07/02. DOI: 10.2459/jcm.0000000000000005.

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29. Schmidt RJ and Dalton CL. Treating anemia of chronic kidney disease in the primary care setting: cardiovascular outcomes and management recommendations. Osteopath Med Prim Care 2007; 1: 14. 2007/10/04. DOI: 10.1186/1750-4732-1-14.

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