HQ Team
February 2, 2023: GSK Plc., a British global pharmaceutical company, announced the FDA had approved an oral drug to treat anaemia arising from chronic kidney disease in patients who have been on dialysis for four months.
Jesduvrog is the first innovative medicine for anaemia treatment in over 30 years, and the only HIF-PHI approved in the U.S., providing a new oral, convenient option for patients in the U.S. with anaemia of chronic kidney disease (CKD) on dialysis, according to a company statement.
HIF-PHIs activate the HIF oxygen-sensing pathway and are efficacious in correcting and maintaining haemoglobin levels in patients with non–dialysis- and dialysis-dependent CKD.
HIF-PHIs also reduce hepcidin levels and modulate iron metabolism, increasing total iron binding capacity and transferrin levels and potentially reducing the need for iron supplementation.
Hepcidin is a protein that is encoded by the HAMP gene. It is a vital regulator of iron entry into mammals’ circulation.
First oral treatment
On February 1, 2023, the U.S. Food and Drug Administration approved Jesduvroq tablets (daprodustat) as the first oral treatment for anaemia of CKD patients, according to a statement from the regulator.
Jesduvroq was disapproved of for patients who are not on dialysis. Other FDA-approved treatments for this condition are injected into the blood or under the skin.
“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 anaemia,” said Ann Farrell, M.D., 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. Patients can consult their healthcare providers to select the most appropriate option.”
More than a half million adults in the U.S. have chronic kidney disease requiring dialysis — a treatment that filters the blood and removes excess fluid from the blood.
Kidneys produce an erythropoietin hormone, which signals the body to make red blood cells.
Erythropoietin
On dialysis, the kidneys cannot produce enough erythropoietin in a person with chronic kidney disease, leading to reduced numbers of red blood cells.
Jesduvroq increases erythropoietin levels. The effectiveness of Jesduvroq was established in a randomized study of 2,964 adults receiving dialysis.
In this study, adults received either oral Jesduvroq or injected recombinant human erythropoietin, a standard of care treatment for patients with anaemia due to chronic kidney disease.
Jesduvroq raised and maintained the haemoglobin — the protein in red blood cells that carries oxygen and is a standard measure of anaemia — within the target range of 10-11 grams/deciliter, similar to the recombinant human erythropoietin.
Boxed warning
Jesduvroq has a boxed warning for an increased risk of thrombotic vascular or blood clotting events, including death, heart attack, stroke, and blood clots in the lungs, legs, or dialysis access site.
The oral drugs’ warnings and precautions include a risk of hospitalization for heart failure, worsening increase of blood pressure, stomach erosions and gastrointestinal bleeding.
Jesduvroq is not approved for patients with anaemia due to chronic kidney disease who are not on dialysis because its safety has not been established in that population.
The most common side effects of Jesduvroq include high blood pressure, thrombotic vascular events, abdominal pain, dizziness and allergic reactions.
According to the FDA, patients should not use Jesduvroq if they also take certain drugs that cause increased levels of Jesduvroq or if they have uncontrolled high blood pressure.
‘More options for patients’
Tony Wood, President and Chief Scientific Officer, GSK, said: “Over the last several decades, there has been little innovation in anaemia of CKD. We are proud to have developed Jesduvroq as a new oral treatment with a patient desire for more options.”
The FDA approval was based on results from the ASCEND-D trial, assessing the efficacy and safety of Jesduvroq for the treatment of anaemia of CKD.
Trial results were published in the New England Journal of Medicine.
A chronic kidney disorder is an increasing global health burden affecting 700 million patients worldwide, with an estimated one in seven patients also developing anaemia.
CKD is characterized by progressive loss of kidney function. Anaemia is an essential and frequent complication of CKD and is associated with increased morbidity, mortality and reduced quality of life.
It is often poorly diagnosed and under-treated in patients with early-stage CKD. It affects approximately 39 million people in the U.S., of whom about 6 million are also affected by anaemia.
Debilitating condition
When left untreated or undertreated, anaemia of CKD is associated with poor clinical outcomes and a substantial burden on patients and healthcare systems. There is an unmet need for oral treatment options with efficacy and safety comparable to current treatments.
LaVarne Burton, President and Chief Executive Officer of American Kidney Fund, said: “Anaemia of CKD can be a debilitating condition that is challenging to manage. This news means that patients on dialysis who are living with anaemia of CKD now have another treatment option to help manage their anaemia.”
A marketing authorization application for daprodustat is currently under review with the European Medicines Agency, with a regulatory decision anticipated in the first half of 2023.
In June 2020, daprodustat tablets were approved by Japan’s Ministry of Health, Labour and Welfare for the treatment of patients with anaemia of CKD.
There are approximately 810,000 patients who are at end-stage renal disease in the U.S. Of this, 558,000 patients receive dialysis and 481,000 receive hemodialysis, and 77,000 receive home or peritoneal dialysis.
