HIF PROLYL

HYDROXYLASE

INHIBITORS: THE FUTURE

OF ANAEMIA

MANAGEMENT IN CKD?

Danilo Nebres Senior Research Nurse King’s College Hospital, London, UK

ESA therapy – the last 25 years

1990

Epoetin alfa (Eprex)

Epoetin beta (NeoRecormon)

ESA therapy – the last 25 years

2001

2007

ESA therapy vs HIF stabilisers

ESA therapy vs HIF stabilisers

• HIF is the major driver of EPO gene production

What is HIF? (hypoxia-inducible factor)

• new class of drug in advanced clinical development

• orally-active

• HIF stabilisers stabilise HIF by inhibiting an enzyme

called prolyl hydroxylase

• More HIF = more EPO

• More EPO = more haemoglobin

What are HIF stabilisers?

Results – efficacy Molidustat increases Hb level in a dose-dependent fashion

Macdougall et al; ERA-EDTA Congress, Vienna, May 2016.

Response to treatment

• Feeling stronger

• Feeling less fatigue

• Less shortness of breath

• More energetic

• Able to do ADL with less assistance

Product Manufacturer Development

Status

FG-4592 Roxadustat FibroGen, Astellas,

AstraZeneca

Phase 3

AKB-6548 Vadadustat Akebia Therapeutics Phase 2/3

BAY 85-3934 Molidustat Bayer Phase 2

GSK1278863 Daprodustat GlaxoSmithKline Phase 2/3

HIF stabilisers in development

Potential advantages of HIF stabilisers

• Oral / Tablet form

• More cost-effective?

• Less hospital appointments for patients

• Particularly useful in non-dialysis CKD

Conclusions – HIF stabilisers

• New orally-active drug class in development

• Effective in treating anaemia in CKD patients

• Preliminary experience in our unit positive

• Still reasonably early days

– long-term safety not proven

• Phase 3 results awaited with interest

Acknowledgements:

• Sponsors

– Astellas

– Bayer

• CRO’s

– INC

– Covance

Acknowledgements:

• Prof Iain Macdougall • The Renal Research team