BioPharma, Pharma

GSK Gets FDA Nod for Drug Treating Anemia From Chronic Kidney Disease

The FDA approved GSK drug Jesduvroq for treating anemia in patients with chronic kidney disease. The once-daily pill is the first oral medicine to pass FDA muster in this indication, giving patients a more convenient alternative to injectable anemia therapies.

Anemia caused by chronic kidney disease can be treated with injectable drugs but various pharmaceutical industry players have been pursuing alternatives that offer patients the convenience of a pill. A GSK medicine has won FDA approval as the first pill in the drug class, a decision that comes after the agency turned down applications from two other contenders.

Approval of GSK drug daprodustat, brand name Jesduvroq, covers only adults who have been receiving dialysis treatments for at least four months, a narrower patient population that tracks with the recommendation of an FDA advisory committee last October. Though these advisors supported approval in dialysis patients, they voted against the drug’s use in those who aren’t on dialysis, saying the risks do not outweigh the benefits in this patient group. The Jesduvroq label carries a black box warning stating that the drug’s potentially fatal cardiovascular risks include heart attack, stroke, and blood clots in lungs, legs, or the dialysis access site.

According to the FDA, more than a half million adults in the U.S. have chronic kidney disease that requires dialysis. In such patients, the kidneys are unable to produce enough erythropoietin, a hormone that signals the body to make red blood cells. Low erythropoietin levels lead to anemia. Available treatments include erythropoietin stimulating agents (ESAs), drugs that are engineered versions of erythropoietin. But these injectable medicines must be administered in a clinical setting on a regular basis—a burden for patients and their caregivers.

Jesduvroq is designed to block hypoxia-inducible factor prolyl hydroxylase (HIF-PH). Blocking these enzymes stabilizes hypoxia-inducible factors, proteins that play a role in the body’s response to low oxygen. In low-oxygen conditions, the body produces more erythropoietin to prompt the production of more oxygen-carrying red blood cells. HIF-PH inhibitors trigger that activity via small molecules formulated as pills.

FDA approval of Jesduvroq is based on results of a Phase 3 study that enrolled 2,964 patients who were receiving dialysis. The GSK drug raised hemoglobin levels and maintained them in a range comparable to levels in patients treated with ESOs. The most common side effects reported from the trial include high blood pressure, thrombotic vascular events, abdominal pain, dizziness, and allergic reactions. The trial results were published in 2021 in the New England Journal of Medicine.

“Over the last several decades, there has been little innovation in anemia of [chronic kidney disease],” GSK President and Chief Scientific Officer Tony Wood said in a prepared statement. “We are proud to have developed Jesduvroq as a new oral treatment where there is a patient desire for more options.”

Other companies have advanced HIF-PH inhibitors through pivotal studies only to fall short at the FDA. In 2021, the FDA rejected FibroGen’s roxadustat, a drug that was previously approved in China, Japan, Chile, and South Korea. Last March, the agency turned down Akebia Therapeutics drug vadadustat and asked for another clinical trial to show that its benefits outweigh safety risks. Akebia is appealing the FDA’s rejection of of vadadustat, a drug that is approved in Japan and is under regulatory review in Europe.

Jesduvroq was first approved in 2020 in Japan, where it is marketed as Duvroq. The GSK drug is currently under review in Europe; a regulatory decision there is expected in the first half of this year.

Photo by GSK