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After rivals’ FDA rebuffs, GSK targets class-first oral approval in chronic kidney disease anemia

Could the third time be the charm for an oral HIF-PH inhibitor in the U.S.? GlaxoSmithKline certainly hopes so, with its potential first-in-class medicine now officially up for a decision at the FDA by early next year.

The FDA has accepted GSK’s application for daprodustat as an oral therapy for patients with anemia of chronic kidney disease (CKD), the company said Tuesday. The FDA plans to deliver its daprodustat verdict by Feb. 1, 2023, GSK said.

The move follows high-profile FDA rejections of two other HIF-PHI class members in anemia. Those are Akebia Therapeutics and Otsuka’s vadadustat, swatted down in March, and AstraZeneca and Fibrogen’s roxadustat, which was rebuffed back in August.

Safety concerns weighed heavily on both of the regulator’s decisions.

Daprodustat’s application, meanwhile, leverages data from GSK’s Ascend phase 3 clinical program, which covered five pivotal trials weighing the safety and efficacy of the med in anemia patients “across the spectrum of CKD,” GSK said. The company also published data from key cardiovascular outcomes trials in the New England Journal of Medicine in November. Those heart studies looked at both CKD patients on dialysis and those who were not.

Both cardiovascular outcomes trials, dubbed Ascend-ND and Ascend-D, met their primary safety and efficacy endpoints, GSK added.

Overall, daprodustat’s studies showed the drug helped improve or maintain target hemoglobin levels without an increase of major cardiovascular events versus standard of care—an erythropoietin stimulating agent (ESA)—across both dialysis and non-dialysis patients, GSK said.

Anemia is an “important and frequent” complication of chronic kidney disease, but it’s often “poorly diagnosed and undertreated in patients with early-stage CKD, such as those not on dialysis,” the company pointed out.

Of the more than 700 million patients worldwide estimated to suffer from CKD, about 14% have anemia, the drugmaker said.

Circling back to Akebia and Otsuka’s vadadustat, Akebia CEO John Butler last month voiced “extreme disappointment and frustration” after the FDA handed down its complete response letter (CRL), which noted safety concerns for the drug such as higher risks of thromboembolic events and liver injury.

In the wake of its rejection, Akebia earlier this month telegraphed plans to trim its workforce by about 42% across “all areas of the company.”

As for AZ and Fibrogen’s roxadustat, the FDA in August told the partners they’d need to run additional clinical studies to reapply with their drug.

After digging deeper into roxadustat’s clinical data, FDA reviewers linked the drug to increased risk of death, blood clots, serious infections and more versus erythropoietin therapy in dialysis patients and placebo in the non-dialysis cohort.

But AZ and FibroGen haven’t given up on roxadustat just yet: The partners in November said they’d scheduled a meeting with the FDA to hash out a potential path forward for the drug, which is approved in China, Japan and Europe as Evrenzo.

GSK’s daprodustat also boasts an approval in Japan, where the drug carries the Duvroq moniker to treat patients with renal anemia. The European Medicines Agency (EMA) in March, meanwhile, accepted daprodustat’s marketing application, which is now under review. GSK plans more filings this year.

Like daprodustat and roxadustat, Akebia and Otsuka’s vadadustat has also been endorsed in Japan, where local partner Mitsubishi Tanabe Pharma sells the drug under the brand name Vafseo.