AstraZeneca finally drops roxadustat US rights after FDA rejection, trial failure

Phase 3Drug ApprovalExecutive ChangeFinancial StatementClinical Result
AstraZeneca finally drops roxadustat US rights after FDA rejection, trial failure
Source: FiercePharma
As AstraZeneca walked away, FibroGen said it's still looking to partner up on roxadustat in anemia associated with myelodysplastic syndromes despite a phase 3 trial flop.
AstraZeneca and FibroGen have finally reached the end of the road for their U.S. collaboration on the oral anemia drug roxadustat.
More than two years after a high-profile FDA rejection, AstraZeneca has returned rights to the HIF-PH inhibitor in the U.S. and certain other countries but retained an interest in China and South Korea, where the drug is approved under the brand name Evrenzo.
The announcement comes nearly 10 months after roxadustat failed in a phase 3 trial in anemia patients with a group of blood cell disorders called myelodysplastic syndromes (MDS). The trial flop appeared to halt roxadustat’s path to the U.S. market after the FDA in 2021 turned it down in anemia associated with chronic kidney disease, although FibroGen is still hanging onto hope in some uses.
Once holding the potential as a first-in-class breakthrough, roxadustat showcased how the entire HIF-PH inhibitor class fell short of lofty market expectations.
Besides an oral convenience edge, roxadustat was once thought to be safer than standard-of-care erythropoietin-stimulating agents. But FibroGen later admitted that its team had manipulated the phase 3 analysis to make the drug look better than it was in reality. Things got worse when an FDA internal review flagged more safety problems, including an increased risk of death, blood clots and infections.
After roxadustat got the inevitable FDA complete response letter, FibroGen and AZ never reached a deal on the plan for a new trial, which was required by the FDA for any potential refiling.
Akebia Therapeuticsvadadustat faced the same fate in 2022. Then, the HIF-PH inhibitor class received its first FDA nod in early 2023, when GSK’s Jesduvroq, or daprodustat, got the green light to treat anemic chronic kidney disease patients who have been reliant on dialysis.
Akebia’s resubmission for vadadustat in that subset of patients was accepted by the FDA in October, and a decision is expected by March 27.
Although Evrenzo is approved in multiple countries outside the U.S., its commercial performance has mostly been disappointing, except for China. In early 2023, Astellas, which is responsible for selling Evrenzo in Japan and Europe, took an impairment loss worth 47.1 billion Japanese yen ($313 million), citing lower-than-expected sales.
By comparison, Evrenzo is thriving in China, which in 2019 became the first country to approve the med. Through a joint venture between AZ and FibroGen, Evrenzo generated $284 million in sales in China in 2023, a healthy rate of 36% growth year over year. That translated into $101 million in revenue for FibroGen.
For 2024, FibroGen expects Evrenzo’s China sales will continue to grow to a range from $300 million to $340 million despite a 7% price reduction from renewed coverage under the country’s national insurance scheme, the company’s CFO Juan Graham told investors on a call Monday. The company also expects a mid-2024 decision in China for Evrenzo as a treatment for patients with chemotherapy-induced anemia based on a China-only trial win.
Meanwhile, FibroGen hasn’t given up on the drug in the U.S. With AZ’s exit, FibroGen now has the opportunity to potentially partner roxadustat in certain indications with high unmet need, such as anemia from MDS, the company’s newly minted CEO Thane Wettig said on the Monday call. Wettig, who was previously FibroGen’s chief commercial officer, became the company’s CEO in October after serving as the interim chief for a short period of time.
In the phase 3 MATTERHORN trial, roxadustat already failed to beat placebo at improving transfusion independence among patients with transfusion-dependent lower-risk MDS. But Wettig noted a “statistically significant and clinically meaningful” advantage for roxadustat in certain patients with a higher transfusion burden at baseline.
“Based on these results, we continue to believe that roxadustat represents an important potential therapy for patients in the U.S. and other territories,” Wettig said.
As roxadustat’s story appears largely settled, FibroGen investors are focusing on the company’s lead candidate pamrevlumab. FibroGen on Monday said it expects phase 3 readout from the LAPIS trial for the drug in locally advanced pancreatic cancer in the second quarter. Simultaneously, pamrevlumab is being evaluated in the Pancreatic Cancer Action Network’s adaptive platform trial called Precision Promise in metastatic pancreatic cancer.
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