FibroGen's roxadustat fails in 2nd act, endangering AstraZeneca partnership

After a high-profile FDA rejection in chronic kidney disease (CKD), FibroGen devised a new plan for the oral anemia drug roxadustat in the U.S. Now, that dream is fading, too.

Roxadustat failed to move the needle in anemia patients with the blood cell disorders myelodysplastic syndromes (MDS), FibroGen said Friday. The phase 3 MATTERHORN trial missed its primary efficacy endpoint measuring the rate of transfusion independence among patients with transfusion-dependent lower-risk MDS.

Numerically, roxadustat performed better than placebo. Of those who took the FibroGen drug, 47.5% didn’t need a transfusion for at least 56 consecutive days during a 28-week trial period. By comparison, 33.3% achieved transfusion independence in the control group.

FibroGen didn’t say anything about regulatory plans after the trial miss. The company is scheduled to report its first-quarter results on May 8. Even if it were to consider a filing, the FDA likely would not approve a drug based on a failed trial.

The trial failure puts FibroGen’s U.S. partnership with AstraZeneca in serious danger. MDS has been FibroGen’s salvage plan for roxadustat in the U.S. after the FDA rejected the drug in CKD-related anemia in 2021. Afterward, the two companies couldn’t agree on funding a new trial to support another CKD filing in the U.S.

FibroGen and AZ tied the knot on roxadustat way back in 2013. The agreement provides AZ the right to terminate the deal upon negative clinical results and other developmental, regulatory or commercialization setbacks, according to FibroGen’s security filings.

A FibroGen spokesperson declined to comment, pointing to its upcoming first-quarter report. AZ didn’t immediately reply to Fierce Pharma’s inquiry.

Roxadustat belongs to the novel HIF-PHI class of oral meds. It once carried blockbuster sales hopes, and some experts thought it could replace treatment with erythropoiesis-stimulating agents (ESAs), which require either infusions or injections. But a slew of safety problems flagged by the FDA, including blood clots and serious infections, eventually led to a regulatory slapdown.

Since then, GSK’s rival drug daprodustat has won FDA approval for dialysis-dependent patients with CKD and is now branded as Jesduvroq. Elsewhere, Akebia Therapeutics is appealing a 2022 FDA rejection for vadadustat.

Meanwhile, roxadustat hasn’t had much success outside the U.S. With approvals in China covering both dialysis and non-dialysis patients, the drug reeled in $61 million sales for AZ in the first quarter.

Astellas, who owns roxadustat under the brand Evrenzo in Japan and Europe, just booked a 47 billion Japanese yen ($348 million) impairment charge based on lower-than-expected sales projections for the drug.

In Japan, competition is fierce within the HIF-PHI class given all three agents are approved there. In Europe, roxadustat hasn’t been able to differentiate itself from existing ESAs, Astellas CEO Naoki Okamura told investors on a call last week.

Roxadustat’s failure in MDS is also good news for Bristol Myers Squibb. The New York pharma’s Reblozyl in 2020 became the first new treatment option for MDS in more than a decade thanks to an FDA go-ahead in patients who’ve failed on an ESA.