Status on FDA Advisory Committee Vote on Roxadustat in Chronic Kidney Disease Anemia | Small molecules
Status on FDA Advisory Committee Vote on Roxadustat in Chronic Kidney Disease Anemia
Category: Small Molecules
Posted on Friday, July 16, 2021 10:03 AM
LONDON, United Kingdom I July 16, 2021 I The Food and Drug Administration (FDA) Cardiovascular and Renal Drug Advisory Committee (CRDAC) voted 13 to 1 that the benefit-risk profile of roxadustat does not support the approval of treatment for anemia in the ‘chronic renal failure (CRF) in non-dialysis dependent adult patients (NDD) and 12 to 2 that the benefit-risk profile of roxadustat does not support the approval of treatment for anemia in CRF in dependent adult patients dialysis (DD).
The FDA will consider voting, independent opinions, and expert recommendations when reviewing the New Drug Application (NDA) and is not bound by the committee’s recommendation.
The safety and efficacy of roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, has been demonstrated in the phase III program involving more than 8,000 patients and published in five journal articles. with reading committee.
Mene Pangalos, Executive Vice President, R&D BioPharmaceuticals, said, “New solutions are needed for the six million people in the United States affected by anemia from chronic kidney disease. While we are disappointed with today’s outcome, we will continue to work closely with our partner FibroGen and the FDA to determine the way forward for roxadustat.
Earlier this year, the FDA confirmed that it would convene a CRDAC meeting to review the NDA for roxadustat and requested additional clinical data clarification analyzes to support the assessment. The FDA has not announced when it will make its final decision on roxadustat NDA.
The CRDAC provides independent expert advice to the FDA, reviews and assesses the available data regarding the safety and efficacy of new and potential drugs on the market for use in the treatment of cardiovascular (CV) and kidney disorders.1
Roxadustat is approved in a number of countries, including China, Japan, Chile and South Korea for the treatment of CKD anemia in adult NDD and DD patients. It is under regulatory review in other jurisdictions, including the European Union, where it recently received a positive opinion from the CHMP.
Anemia can be a serious condition in which patients have insufficient red blood cells and low levels of hemoglobin, a protein in red blood cells that carries oxygen to cells throughout the body.1 CKD anemia frequently causes severe fatigue, cognitive dysfunction, and decreased quality of life, and is associated with an increased risk of hospitalization, CV complications, and death.1.2 Severe anemia is common in patients with CKD, cancer, myelodysplastic syndrome (MDS), inflammatory diseases, and other serious illnesses. Anemia is particularly prevalent in patients with CRF.2,3,4 CRF affects 840 million patients worldwide and is usually progressive, characterized by a progressive loss of kidney function which can eventually lead to kidney failure.5.6
Phase III program
The Phase III program included more than 8,000 patients and was led by AstraZeneca, FibroGen and Astellas Pharma Inc. (Astellas). The OLYMPUS, ALPS and ANDES trials evaluated roxadustat versus placebo in NDD-CKD patients. ROCKIES, SIERRAS and HIMALAYAS evaluated roxadustat versus epoetin alfa in patients with DD-CKD and incident dialysis (ID). HIMALAYAS evaluated roxadustat versus epoetin alfa in patients with ID; ROCKIES and SIERRAS included DI patients and prevalent dialysis patients.
Roxadustat, an oral drug, could be the first in a new class of treatments called oral HIF-PH inhibitors that promote erythropoiesis, or red blood cell production, through increased endogenous erythropoietin production, absorption and absorption. improved iron mobilization and reduced hepcidin. Roxadustat is also in clinical development for anemia associated with MDS and for anemia induced by chemotherapy.
Roxadustat is approved in China, Japan, Chile and South Korea (under the name Evrenzo), for the treatment of anemia in CRF in adult NDD and DD patients. In Europe, the marketing authorization application for Evrenzo for the treatment of anemia in CRF in NDD and DD patients was submitted by Astellas and accepted by the European Medicines Agency for review in May 2020 and is under final regulatory review following a positive opinion of the EU CHMP in June 2021.
AstraZeneca and FibroGen are collaborating on the development and commercialization of roxadustat for the potential treatment of anemia in the United States, China and other countries of the Americas, Australia and New Zealand, as well as South Asia. South East. Astellas and FibroGen are collaborating on the development and commercialization of roxadustat for the potential treatment of anemia in Japan, Europe, Turkey, Russia and the Commonwealth of Independent States, the Middle East and South Africa.
AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM), which is part of BioPharmaceuticals, is one of AstraZeneca’s three disease areas and is a key growth engine for the Company. By following science to more clearly understand the underlying links between the heart, kidneys and pancreas, AstraZeneca is investing in a portfolio of organ protection drugs and improving outcomes by slowing disease progression, reducing disease. risks and combating co-morbidities. The Company’s ambition is to alter or halt the natural course of CVRM diseases and potentially regenerate organs and restore function, continuing to provide transformative science that improves treatment practices and the CV health of millions. patients around the world.
AstraZeneca (LSE / STO / Nasdaq: AZN) is a global science-based biopharmaceutical company focused on the discovery, development and commercialization of prescription drugs in oncology and biopharmaceuticals, including cardiovascular, renal and metabolism, and respiratory and immunology. Based in Cambridge, UK, AstraZeneca operates in more than 100 countries and its innovative medicines are used by millions of patients around the world. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
1. US Food & Drug Administration. Cardiovascular and Renal Drugs Advisory Committee; 2021 [cited 2021 Jul 7]. Available at: URL: https://www.fda.gov/advisory-committees/human-drug-advisory-committees/cardiovascular-and-renal-drugs-advisory-committee.
2. National Institute of Diabetes, Digestive and Kidney Diseases. Anemia in chronic kidney disease; 2014 [cited 2021 Jul 7]. Available at: URL: https://www.niddk.nih.gov/health-information/kidney-disease/anemia.
3. Babitt JL, et al. Mechanisms of anemia in CRF. J Am Soc Nephrol. 2012; 23: 1631-1634.
4. Mayo Clinic. Anemia; 2019 [cited 2021 Jul 7]. Available at: URL: https://www.mayoclinic.org/diseases-conditions/anemia/symptoms-causes/syc-20351360.
5. Mayo Clinic. Myelodysplastic syndromes; 2021 [cited 2021 Jul 7]. Available at: URL: https://www.mayoclinic.org/diseases-conditions/myelodysplastic-syndrome/symptoms-causes/syc-20366977.
6. Jager KJ, et al. One issue for advocacy and communication: Worldwide, more than 850 million people suffer from kidney disease. Nephrol dial graft. 2019; 34 (11): 1803-1805.
7. Bikbov B et al. Global, regional and national burden of chronic kidney disease, 1990-2017: a systematic review for the Global Burden of Disease Trial 2017.The Lancet 2020; 395 (10225): 709–33.