UPDATE:
On April 6, 2021 Fibrogen announced that the analysis of the cardiovascular outcomes was adjusted after the data was unblinded. When the data was reanalyzed without this adjustment roxadustat is less impactful. Importantly for this NephJC discussion, the previously impressive MACE and MACE+ advantage for incident dialysis is no longer found. Roxadustat remains non-inferior in all outcomes, though the confidence intervals have widened.
Episode 031: Two articles on roxadustat as it closes in on FDA approval:
The Filtrate:
Jennie Lin
Joel Topf
Swapnil Hiremath
Nayan Arora
And two special guests:
Robert Provenzano Lead author of the pooled analysis. Twitter.
Pascale Khairallah Nephrologist at Baylor College of Medicine in Texas. She is on the NephMadness executive team and wrote the Anemia region this year.
Show Notes:
NephJC coverage of these two roxadustat trials.
The Normal Hematocrit trial, Besarab et al NEJM 1998
The NephJC coverage of Besarab et al and the Coyne re-analysis
NephMadness Anemia missteps from 2016
FDA guidance on diabetes drugs - paradoxically being reversed now
NephJC stats post on non-inferiority from Manasi Bapat
The Flozins activate the HIF pathway
The Anemia region of NephMadness: https://ajkdblog.org/2021/03/04/nephmadness-2021-hif-phis-the-new-kids-on-the-block-in-anemia-therapy-and-much-more/
The vadudustat phase three data presented at Kidney Week
Daft Punk break up video, Epilogue: https://www.youtube.com/watch?v=DuDX6wNfjqc
The first KeyLime episode with Dr Kimberly Manning
How can a non inferiority study show superiority? Figure below from Schumi & Wittes