4. Roxadustat

AstraZeneca has rights to roxadustat in the U.S. and China, the latter of which has already approved and covered it in both nondialysis-dependent and dialysis-dependent chronic kidney disease patients with anemia. (AstraZeneca)

Drug: Evrenzo (roxadustat)
Companies: FibroGen, AstraZeneca and Astellas
Used for: anemia associated with kidney disease
Est. 2024 sales: $1.488 billion

FibroGen’s anemia drug Evrenzo (roxadustat) has already won approvals and national coverage for both nondialysis-dependent and dialysis-dependent kidney patients in China, where it shares rights with AstraZeneca. In Japan, its partner Astellas has nabbed a green light for dialysis patients.

In the U.S., FibroGen filed for approval in both indications in December 2019. EvaluatePharma predicted the drug could turn up $1.488 billion by 2024 sales. Another team of analysts is a lot more bullish, though; SVB Leerink figures China alone could deliver $1.4 billion in 2025, and that its global number could range between $3 billion and $3.5 billion by that time.

Roxadustat is the first in the hypoxia-inducible factor prolyl hydroxylase inhibitor class to be approved anywhere. Different from Amgen and Johnson & Johnson’s standard-of-care injection Epogen/Procrit, oral roxa corrects anemia by mimicking a response to reduced oxygen levels.

Pooled phase 3 analyses showed roxa triggered a significantly higher increase in hemoglobin levels in dialysis-dependent patients compared with Epogen/Procrit, with mean change from baseline averaged over weeks 28 to 52 standing at 1.22 g/dL and 0.99 g/dL respectively. In nondialysis-dependent patients, the numbers were 1.85 g/dL for roxa and 0.13 g/dL with placebo. For men, normal hemoglobin levels range from 14.0 g/dL to 17.5 g/dL; for women, it's between 12.3 g/dL and 15.3 g/dL, according to the Cleveland Clinic, though the standards vary slightly among institutions. 

Investigators pitted roxa against placebo in nondialysis patients because traditional erythropoietin-stimulating agent therapy isn't approved for that group; the cardiovascular risks are too great. Roxa hopes it could make a difference for these patients—and access to that market is a much bigger opportunity than sticking to dialysis patients alone. According to the CDC's most recent data, about 4 million people in the U.S. know they have chronic kidney disease in 2019. In contrast, according to U.S. Renal Data System data cited by AZ, about 509,000 U.S. patients were receiving dialysis in 2016.

In the pooled analysis, the risk of major adverse CV events observed in the roxa patients was comparable to that in the placebo arm. However, a hazard ratio of 1.08 means roxa’s rate was slightly higher, though not statistically significant.

That trend worried some investors, who feared the FDA might stonewall roxa in the larger nondialysis indication. FibroGen says the idea is erroneous.

RELATED: New FibroGen CEO Conterno cut his post-Lilly 'vacation' short. Why? Roxadustat

Enrique Conterno, FibroGen’s newly installed CEO and a 27-year Eli Lilly veteran who previously headed the Indianapolis pharma’s diabetes operations, recently told SVB Leerink analyst Geoffrey Porges that many diabetes drugs had won CV label expansions with much higher hazard ratios, all the way up to 1.8.

Investors have another worry, too: Because of the Centers for Medicare & Medicaid Services’ “bundled” payment system for U.S. dialysis treatments and services, they're concerned that CMS might be reluctant to reimburse a new drug outside that package. But FibroGen management pointed Porges to a relatively new rule called the Transitional Drug Add-on Payment Adjustment—which allows additional payments for new therapies—suggesting the company will apply for coverage through that path.

Roxa could face some in-class competition soon. These include GlaxoSmithKline’s daprodustat, filed for approval in Japan under a collaboration with Kyowa Kirin. And Akebia Therapeutics and local partner Mitsubishi filed their rival, vadadustat, in Japan in July 2019. In the U.S., Akebia has teamed up with Japanese pharma Otsuka on the anemia treatment.

4. Roxadustat