FibroGen has topline results from pooled analyses of roxadustat Phase 3 program

FibroGen (FGEN) announced topline results from the pooled safety analyses of the global Phase 3 program for roxadustat, an inhibitor of hypoxia-inducible-factor, or HIF, prolyl hydroxylase activity, or HIF-PHI. The global pivotal Phase 3 trials were conducted by FibroGen and collaboration partners AstraZeneca (AZN) and Astellas Pharma (ALPMY), for treatment of anemia in chronic kidney disease, or CKD, patients across the non-dialysis-dependent, or NDD, incident dialysis, and dialysis-dependent, or DD, CKD populations, enrolled from more than 50 countries. These pooled analyses of adjudicated events for safety assessment of roxadustat are part of the overall benefit-risk assessment. For the planned new drug application, or NDA, submission to the FDA, one of the safety endpoints to be evaluated is Major Adverse Cardiac Events, or MACE, a composite endpoint of all-cause mortality, stroke and myocardial infarction, in pooled analyses against placebo in NDD and against epoetin alfa in DD from the pivotal Phase 3 trials. The NDA submission package to the FDA will be based on the totality of evidence, and the company will continue to discuss the specific statistical standards with the FDA. For the European Medicines Agency, it was agreed that the primary safety assessment is MACE+, a composite endpoint of MACE plus heart failure requiring hospitalization and unstable angina requiring hospitalization. In the pooled analyses of around 4,000 dialysis patients, the upper bound of the 95% confidence interval was below the pre-specified non-inferiority margin for the time to first MACE+ analyses. Based on the MACE safety analyses of this population, the company believes there is no clinically meaningful difference in risk of MACE between roxadustat and epoetin alfa. The roxadustat global Phase 3 program enrolled over 1,500 incident dialysis patients, a subpopulation of DD-CKD population, which the company believes offers a better setting for comparing roxadustat to epoetin alfa than the stable dialysis population, that is stable on both dialysis and erythropoiesis stimulating agent. Roxadustat demonstrated superiority to epoetin alfa in the time to first MACE+ in this subpopulation. In the MACE analysis, there is a trend toward reduced risk for patients on roxadustat, compared to epoetin alfa. In the non-dialysis pool of approximately 4,300 patients, non-inferiority was demonstrated for roxadustat compared to placebo in the time to first MACE+, based on the upper bound of the 95% CI being below the prespecified non-inferiority margin. Based on the MACE safety analyses of this population, the company believes there is no clinically meaningful difference in risk of MACE between roxadustat and placebo. Of note, multiple MACE and MACE+ analyses in NDD-CKD from the roxadustat global Phase 3 program are being performed in intent-to-treat analyses that demonstrated comparability of roxadustat to placebo. ITT is among the several statistical methods that the company will discuss with the FDA. In these analyses, roxadustat was comparable based on a commonly applied non-inferiority margin of 1.3.

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