Turns out, the third time is the charm.
After two prior FDA rejections for oral anemia drugs in the hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) drug class, GSK’s daprodustat, branded as Jesduvroq, has won a class-first approval. Specifically, the drug is approved to treat patients with anemia caused by chronic kidney disease who have been on dialysis for at least four months.
GSK hoped to gain an approval to treat patients who don't require dialysis, but the FDA concluded the drug's safety “has not been established in that population.”
That's not a complete surprise. An FDA advisory committee only endorsed the drug in the dialysis-dependent patient population when it met in October.
Jesduvroq is a member of a drug class that hasn’t had much success in the past. The FDA has already rejected meds from Akebia Therapeutics and Otsuka, plus from AstraZeneca and Fibrogen, largely because of safety concerns. Higher risks of blood clots and liver injuries were cited as safety issues for Akebia and Otsuka’s treatment, while AZ and Fibrogen’s was linked to increased risk of death, blood clots, serious infections and more.
As for GSK's treatment, the company’s commercialization strategy will focus on contracting with dialysis providers, GSK’s chief commercial officer Luke Miels said during a recent interview with Fierce Pharma. The company won’t run additional trials to try again for the non-dialysis population, Miels said at the time.
In clinical trials, Jesduvroq's safety risks in the non-dialysis dependent patient population included "elevated estimated" risks for heart attack and stroke, the FDA noted in its pre-advisory briefing document back in October. This drew hesitancy from the advisory committee, considering approved erythropoiesis-stimulating agents already carry similar risks.
Safety risks, though not concerning enough to thwart an approval, were present in the dialysis patient population as well. Jesduvroq will carry a boxed warning highlighting the increased risk of blood clotting events including death, heart attack, stroke and blood clots in the lungs, legs or the dialysis access site.
Chronic kidney disease (CKD) affects 700 million patients worldwide, with an estimated 1 in 7 patients developing anemia. Anemia of CKD, left untreated or undertreated, leads to “a substantial burden” on both patients and healthcare systems, GSK noted in a statement discussing the advisory committee's decision.
There remains an unmet need for convenient treatment options with safety and efficacy that is comparable to current treatments, the company said in its fourth-quarter results announcement (PDF). Other available treatments are administered as injections.
In Japan, the drug is the market leader and preferred HIF-PHI class member, GSK pointed out last fall. There, it's approved as Duvroq to treat patients with renal anemia due to CKD.