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The FDA approved the first oral agent for chronic kidney disease (CKD)-related anemia for adults on dialysis, the late on Wednesday.

Daprodustat (Jesduvroq) is a once-daily tablet specifically indicated for patients who have been receiving dialysis for at least 4 months.

Acting as a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), daprodustat works by inhibiting the oxygen pathway within the body, stimulating endogenous erythropoietin production and thus raising hemoglobin levels.

All other approved treatment options for this patient population are administered intravenously or by injection -- the most common of which are erythropoietin stimulating agents (ESAs).

"With an oral drug option in addition to the FDA-approved injection options, adults with chronic kidney disease on dialysis now have multiple ways to treat their anemia," said Ann Farrell, MD, director of the division of non-malignant hematology in the FDA's Center for Drug Evaluation and Research.

"This approval demonstrates the FDA's commitment to helping bring a range of therapeutic options to patients with chronic diseases," Farrell added in a statement. "Patients can consult with their healthcare providers to select the option that is most appropriate."

Underpinning the approval was the ASCEND clinical program, which included two phase III trials -- one in the dialysis-dependent population and another for CKD anemia patients not on dialysis.

In the 2,964-participant dialysis trial, patients treated with oral daprodustat had a mean change in hemoglobin level of 0.28±0.02 g/dL from baseline to weeks 28 through 52 versus an average hemoglobin change of 0.10±0.02 g/dL for those on an ESA, a difference that met the trial's prespecified noninferiority margin.

Chair of the ASCEND program's Executive Steering Committee, Ajay Singh, MBBS, MBA, of Brigham and Women's Hospital in Boston, previously told 番茄社区 that daprodustat "has the potential to be transformative for patient care."

Though differences weren't significant, several cardiovascular safety signals in the dialysis-dependent trial favored daprodustat over ESAs.

By restricting approval to the dialysis population, the FDA appears to be in lockstep with recommendations from an advisory panel in the fall. Certain cardiovascular and thromboembolic risks, plus signals for serious gastric/esophageal erosions and acute kidney injury emerged exclusively in the non-dialysis trial.

Another HIF-PHI, , was rejected by the FDA for CKD-related anemia in 2021 due to concerns of thrombotic risks, and multiple other HIF-PHIs are in development.

The most common side effects with daprodustat in the ASCEND program were high blood pressure, thrombotic vascular events, abdominal pain, dizziness and allergic reactions.

Daprodustat's label will carry a boxed warning for an increased risk of thrombotic vascular events including death, heart attack, stroke, and blood clots in the lungs, legs, or dialysis access site. Other warnings on the label include a risk of hospitalization for heart failure, worsening increase of blood pressure, and stomach erosions and gastrointestinal bleeding. Patients with uncontrolled hypertension should not take daprodustat.

"Targeting a hemoglobin level greater than 11 g/dL is expected to further increase the risk of death and arterial venous thrombotic events, as occurs with [ESAs], which also increase erythropoietin levels," said drugmaker . "No trial has identified a hemoglobin target level, dose of Jesduvroq, or dosing strategy that does not increase these risks."

Five dosage strengths will be available (1 mg, 2 mg, 4 mg, 6 mg, and 8 mg), and GSK said that the lowest dose is "sufficient" to reduce the need for red blood cell transfusions, though the agent is not a substitute for red blood cell transfusions for patients who immediately require correction of anemia.

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