The HIF pathway
The HIF (hypoxia-inducible factor) pathway plays a central role in erythropoiesis.
It is the physiological mechanism by which the body responds to low oxygen conditions, such as those experienced at high altitude.
The HIF pathway affects all the key components of eythropoiesis:
- Increases erythropoietin (EPO) production
- Suppresses hepcidin production
- Increases iron absorption, transport and mobilisation
The HIF pathway is critically important to oxygen sensing
In normoxic conditions, the HIF pathway is not activated and the HIF-α subunit is rapidly degraded via HIF prolyl-hydroxylase (HIF-PH):
In hypoxic conditions, the HIF pathway is activated: the HIF-α subunit is not degraded, allowing dimerisation with the HIF-ß subunit and so inducing the transcription and translation of target hypoxia response genes involved in erythropoiesis, including:
In CKD, oxygen sensing via HIF is impaired, and this contributes to the development of anaemia.
But inhibiting the breakdown of HIF offers the opportunity to override the effect of CKD on oxygen sensing as well stimulating the production of erythropoetic genes and their associated proteins.
CKD, chronic kidney disease; HIF, hypoxia-inducible factor; HIF-PH, hypoxia-inducible factor prolyl-hydroxylase; EPO, erythropoietin.
OROXAT: a first-in-class treatment
OROXAT is a HIF-PH inhibitor, a class of drug with a novel mechanism of action.
OROXAT mimics the body's natural response to hypoxia by activating the HIF pathway
OROXAT inhibits HIF-PH, thus preventing breakdown of HIF-α and activating the HIF pathway
This induces transcription and translation of genes involved in erythropoiesis
HIF-PH inhibitors induce activation of the genes responsible for erythropoiesis, but do so in the presence of normal oxygen tension.
OROXAT reduces hepcidin levels and improves iron bioavailability
Through the inhibition of HIF-PH, OROXAT stimulates a coordinated erythropoietic response that not only increases erythropoietin (EPO) levels, but also increases iron mobilisation, as well as helping to overcome the effects of inflammation by suppressing hepcidin.
See how OROXAT works:
OROXAT is indicated for the treatment of adult patients with symptomatic anaemia associated with chronic kidney disease (CKD)
CKD, chronic kidney disease; EPO, erythropoietin; HIF, hypoxia-inducible factor; HIF-PH, hypoxia-inducible factor prolyl-hydroxylase.
OROXAT promotes a coordinated erythropoietic response
By inhibiting HIF-PH, OROXAT stimulates a coordinated erythropoietic response that:
Hb, haemoglobin; HIF-PH, hypoxia-inducible factor prolyl-hydroxylase; RBC, red blood cell.
The place of OROXAT in management of anaemia of CKD
OROXAT has the potential to change the clinical management of anaemia of CKD.
Instead of treating the conditon as a deficiency of EPO or iron, OROXAT addresses multiple factors that contribute to anaemia.
Targeting the HIF pathway with HIF-PHIs may offer an advance in clinical practice by providing a more comprehensive and physiological approach to the management of anaemia of CKD than existing treatments.
OROXAT helps patients with anaemia of CKD:
- To achieve and maintain their target Hb levels
- With a reduced use of IV iron compared to ESA
- And the convenience of oral administration4 with a three times weekly tablet on non-consecutive days
OROXAT (roxadustat) is indicated for treatment of adult patients with symptomatic anaemia associated with chronic kidney disease (CKD)
CKD, chronic kidney disease; EPO, erythropoietin; ESA, erythropoiesis-stimulating agent; HIF, hypoxia-inducible factor; HIF-PHI, hypoxia-inducible factor prolyl-hydroxylase inhibitor; IV, intravenous; TIW, three times weekly.
Why OROXAT?
OROXAT, a first-in-class treatment for adult patients with symptomatic anaemia associated with CKD, is like a breath of fresh air, at high altitude
Innovation
- OROXAT's MoA leads to a coordinated erythropoietic response ultimately resulting in increased haemoglobin production
- OROXAT can help adult patients with symptomatic anaemia associated with CKD achieve and maintain their recommended Hb levels. In clinical studies, less IV iron was used in patients taking OROXAT compared to ESAs
Confidence
- The general safety profile of OROXAT was overall comparable to ESAs for the majority of safety variables evaluated and is reflective of the studied CKD populations
Convenience
- Oral administration with a three times weekly tablet, on non-consecutive days
*Please see OROXAT SmPC for full safety profile and further information on CV and mortality risk.
Reporting Adverse Events
Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to SKF Pharma Ltd. on 0800 783 5018