GlaxoSmithKline has boosted its challenge for the anemia due to chronic kidney disease market, revealing a clean sweep of hits on key endpoints across two phase 3 clinical trials. But with the FDA rejecting AstraZeneca’s rival drug, doubts remain about GSK’s chances of getting to market.
The FDA threw the race to win approval for an oral alternative to erythropoietin stimulating agents wide open earlier this year by hitting AstraZeneca with a complete response letter. The rejection of AstraZeneca’s FibroGen-partnered roxadustat gave Akebia Therapeutics and GSK a shot at getting to market ahead of the one-time front-runner—but also raised concerns that their drugs would face a tough time at the FDA.
GSK set out its case in two publications in The New England Journal of Medicine. Each paper covers a phase 3 clinical trial, with one detailing the performance of GSK’s daprodustat in dialysis setting and the other discussing how it performs in non-dialysis patients. The headline findings are positive, but the precedent of roxadustat points to a tricky path forward.
“Given AZN's roxadustat was recently rebuffed by FDA, safety will be scrutinised, and while we see positives supporting dapro, there remain uncertainties suggesting high risk into a likely late-2022 FDA Advisory Committee meeting,” analysts at Jefferies wrote in a note to investors.
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In both patient populations, GSK showed daprodustat was non-inferior to the standard of care, either Epogen or Aranesp, in terms of change in the hemoglobin level and the first occurrence of a major adverse cardiovascular event such as death, heart attack or stroke. The efficacy data suggest the drug delivers the efficacy of the injectable incumbents in an oral dosage form.
AstraZeneca went to the FDA with data suggesting roxadustat is at least as efficacious as Epogen but still got rejected. The rejection stemmed from worries about safety incidents such as thrombotic events and seizure. As GSK’s daprodustat and Akebia’s vadadustat are part of the same class of drugs as roxadustat, the rejection had potentially negative implications for all of the companies
There are signs daprodustat may be less affected by some of the problems that scuttled roxadustat, with the studies suggesting GSK’s drug is less prone to causing seizures or jumps in hemoglobin. Yet, those positives were offset by a higher rate of gastric erosions than roxadustat and the absence of an iron-sparing benefit. Thrombosis risk may be an issue for both drugs, but GSK thinks it has a shot.
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“GSK is comfortable ASCEND data are robust and interpretable, with five positive trials, no sub-group analysis, and two CVOTs independently showing non-inferiority. Seizure rates were lower with dapro and although there was an imbalance in thromboembolic events in ASCEND-ND, it was small numbers and the principal investigator didn't perceive a real difference,” the Jefferies analysts wrote.
If GSK can get daprodustat to market, it may benefit from the setback to roxadustat. When GSK set out its expectations for daprodustat in June, it looked set to be third to market after roxadustat and vadadustat. At that stage, GSK tipped daprodustat to generate peak sales of 500 million pounds ($674 million) to 1 billion pounds. Now, a bigger prize may be on offer.