FDA Approves Vafseo (vadadustat) for the Treatment of Anemia due to Chronic Kidney Disease in Adult Patients on Dialysis

Akebia Therapeutics, Inc. (Nasdaq: AKBA), a biopharmaceutical company with the purpose to better the lives of people impacted by kidney disease, today announced that the U.S. Food and Drug Administration (FDA) has approved Vafseo® (vadadustat) Tablets for the treatment of anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least three months. Vafseo is a once-daily oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor that activates the physiologic response to hypoxia to stimulate endogenous production of erythropoietin to manage anemia. Vafseo is now approved in 37 countries.

"With the approval of Vafseo in the U.S., we're proud to deliver an alternative treatment option for the hundreds of thousands of Americans on dialysis who are diagnosed with anemia due to CKD," said John P. Butler, Chief Executive Officer of Akebia. "At Akebia we are committed to kidney patients, a dedication that has driven our team to achieve this milestone. We believe this commitment uniquely positions the company to execute a successful launch designed to drive toward a potential new oral standard of care for dialysis patients."

The approval of Vafseo for the treatment of anemia due to CKD in adults who have been receiving dialysis for at least three months is based on efficacy and safety data from the INNO2VATE program and an assessment of post marketing safety data from Japan where VAFSEO was launched in August 2020. Results from the INNO2VATE program were published in the New England Journal of Medicine: (N Engl J Med 2021; 384:1601-1612); (N Engl J Med 2021; 384:1589-1600). See the Important Safety Information section below, including BOXED WARNING regarding increased risk of death, myocardial infarction, stroke, venous thromboembolism and thrombosis of vascular access.

Approximately 500,000 adult patients in the U.S. on dialysis suffer from anemia due to CKD1, which may be associated with many adverse clinical outcomes. The burden of managing uncontrolled anemia in CKD patients can be substantial, both in terms of healthcare costs and the impact on patients, healthcare providers and caregivers. Today, most CKD patients are treated for anemia with injectable erythropoiesis-stimulating agents mostly administered at dialysis centers. "Patients receiving maintenance dialysis would benefit from additional therapeutic options that can effectively increase and maintain hemoglobin concentrations within guideline-recommended target ranges," said Glenn M. Chertow, M.D., M.P.H., Professor of Medicine, Division of Nephrology at Stanford University and Co-Chair of the independent Executive Steering Committee for PRO2TECT and INNO2VATE, the global Phase 3 clinical development programs for Vafseo.

Lori Hartwell, who has had kidney disease since she was a young child, is the Founder and President of the Renal Support Network. She expressed her support of this new therapy for adults with anemia due to chronic kidney disease on dialysis by stating, "Anemia is a debilitating condition that significantly impacts our daily lives. It is promising to see the introduction of innovative treatment options for people fighting anemia."

Akebia intends to commercialize Vafseo in the U.S. with its established commercial team that has deep renal experience and by leveraging its relationship with CSL Vifor, an industry leader in bringing innovative therapies to U.S. dialysis organizations. In line with the approved label, Akebia will execute a launch strategy to drive Vafseo toward the goal of becoming a new oral standard of care for adult dialysis patients.

Mr. Butler added, "We are tremendously grateful for the patients, physicians, investigators, and site coordinators who participated in our clinical trials that led to this important approval. This milestone is the culmination of years of perseverance by Akebia employees and partners committed to bettering the lives of people impacted by kidney disease."

Ref: https://en.wikipedia.org/wiki/Vadadustat

FDA Approves Vafseo (vadadustat) for the Treatment of Anemia due to Chronic Kidney Disease in Adult Patients on Dialysis

FDA Approves Jesduvroq (daprodustat) for Anemia Caused by Chronic Kidney Disease for Adults on Dialysis

GSK plc (LSE/NYSE: GSK) announced the US Food and Drug Administration (FDA)  approval of  Jesduvroq (daprodustat), an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), for the once-a-day treatment of anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least four months. Jesduvroq is the first innovative medicine for anemia treatment in over 30 years and the only HIF-PHI approved in the US, providing a new oral, convenient option for patients in the US with anemia of CKD on dialysis.

The FDA approval is based on results from the ASCEND-D trial, assessing the efficacy and safety of Jesduvroq for the treatment of anemia of CKD in patients on dialysis. Results were published in the New England Journal of Medicine with additional results published in the New England Journal of Medicine supplementary appendix.

The Safety Information for Jesduvroq includes a boxed warning for increased risk of death, myocardial infarction, stroke, venous thromboembolism, and thrombosis of vascular access. Jesduvroq increases the risk of thrombotic vascular events, including major adverse cardiovascular events (MACE). 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 erythropoietin stimulating agents (ESAs), which also increase erythropoietin levels. No trial has identified a hemoglobin target level, dose of Jesduvroq, or dosing strategy that does not increase these risks. Use the lowest dose of Jesduvroq sufficient to reduce the need for red blood cell transfusions. Jesduvroq has not been shown to improve quality of life, fatigue, or patient well-being. Jesduvroq is not indicated for use as a substitute for red blood cell transfusions in patients who require immediate correction of anemia or for treatment of anemia of chronic kidney disease in patients who are not on dialysis.

CKD is an increasing global health burden affecting 700 million patients worldwide, with an estimated one in seven patients also developing anemia.1,2 When left untreated or undertreated, anemia of CKD is associated with poor clinical outcomes and leads to a substantial burden on patients and healthcare systems.3 There is an unmet need for oral treatment options with efficacy and safety comparable to current treatments.

LaVarne Burton, President and Chief Executive Officer, American Kidney Fund, said: “Anemia of CKD can be a debilitating condition that is challenging to manage. This news means that patients on dialysis who are living with anemia of CKD now have another treatment option to help manage their anemia.”

A marketing authorisation 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 anemia of CKD. In Japan, the brand name for daprodustat is Duvroq, where it is the market leader and preferred HIF-PHI.

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

The FDA approval is based on results from the ASCEND-D trial, assessing the efficacy and safety of Jesduvroq for the treatment of anemia of CKD in patients on dialysis. Results were published in the New England Journal of Medicine with additional results published in the New England Journal of Medicine supplementary appendix.

The Safety Information for Jesduvroq includes a boxed warning for increased risk of death, myocardial infarction, stroke, venous thromboembolism, and thrombosis of vascular access. Jesduvroq increases the risk of thrombotic vascular events, including major adverse cardiovascular events (MACE). 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 erythropoietin stimulating agents (ESAs), which also increase erythropoietin levels. No trial has identified a hemoglobin target level, dose of Jesduvroq, or dosing strategy that does not increase these risks. Use the lowest dose of Jesduvroq sufficient to reduce the need for red blood cell transfusions. Jesduvroq has not been shown to improve quality of life, fatigue, or patient well-being. Jesduvroq is not indicated for use as a substitute for red blood cell transfusions in patients who require immediate correction of anemia or for treatment of anemia of chronic kidney disease in patients who are not on dialysis.

CKD is an increasing global health burden affecting 700 million patients worldwide, with an estimated one in seven patients also developing anemia.1,2 When left untreated or undertreated, anemia of CKD is associated with poor clinical outcomes and leads to a substantial burden on patients and healthcare systems.3 There is an unmet need for oral treatment options with efficacy and safety comparable to current treatments.

LaVarne Burton, President and Chief Executive Officer, American Kidney Fund, said: “Anemia of CKD can be a debilitating condition that is challenging to manage. This news means that patients on dialysis who are living with anemia of CKD now have another treatment option to help manage their anemia.”

A marketing authorisation 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 anemia of CKD. In Japan, the brand name for daprodustat is Duvroq, where it is the market leader and preferred HIF-PHI.

The FDA approval is based on results from the ASCEND-D trial, assessing the efficacy and safety of Jesduvroq for the treatment of anemia of CKD in patients on dialysis. Results were published in the New England Journal of Medicine with additional results published in the New England Journal of Medicine supplementary appendix.

The Safety Information for Jesduvroq includes a boxed warning for increased risk of death, myocardial infarction, stroke, venous thromboembolism, and thrombosis of vascular access. Jesduvroq increases the risk of thrombotic vascular events, including major adverse cardiovascular events (MACE). 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 erythropoietin stimulating agents (ESAs), which also increase erythropoietin levels. No trial has identified a hemoglobin target level, dose of Jesduvroq, or dosing strategy that does not increase these risks. Use the lowest dose of Jesduvroq sufficient to reduce the need for red blood cell transfusions. Jesduvroq has not been shown to improve quality of life, fatigue, or patient well-being. Jesduvroq is not indicated for use as a substitute for red blood cell transfusions in patients who require immediate correction of anemia or for treatment of anemia of chronic kidney disease in patients who are not on dialysis.

CKD is an increasing global health burden affecting 700 million patients worldwide, with an estimated one in seven patients also developing anemia.1,2 When left untreated or undertreated, anemia of CKD is associated with poor clinical outcomes and leads to a substantial burden on patients and healthcare systems.3 There is an unmet need for oral treatment options with efficacy and safety comparable to current treatments.

LaVarne Burton, President and Chief Executive Officer, American Kidney Fund, said: “Anemia of CKD can be a debilitating condition that is challenging to manage. This news means that patients on dialysis who are living with anemia of CKD now have another treatment option to help manage their anemia.”

A marketing authorisation 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 anemia of CKD. In Japan, the brand name for daprodustat is Duvroq, where it is the market leader and preferred HIF-PHI.

https://en.wikipedia.org/wiki/Daprodustat

https://go.drugbank.com/drugs/DB11682

FDA Approves Jesduvroq (daprodustat) for Anemia Caused by Chronic Kidney Disease for Adults on Dialysis

FDA Approves Rayaldee (calcifediol) to Treat Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease

OPKO Health, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved Rayaldee (calcifediol) extended release capsules for the treatment of secondary hyperparathyroidism (SHPT) in adults with stage 3 or 4 chronic kidney disease (CKD) and serum total 25-hydroxyvitamin D levels less than 30 ng/mL. Rayaldee is a patented extended release product containing 30 mcg of a prohormone called calcifediol (25-hydroxyvitamin D3).

 calcifediol

"FDA's approval of Rayaldee represents an important milestone for OPKO," noted Dr. Phillip Frost, CEO and Chairman of OPKO. "Rayaldee is the first product to receive FDA approval for this important indication and is one of OPKO's many pharmaceutical products being developed for significant medical problems which will benefit from new treatment options."

Results from two 26 week placebo controlled, double blind phase 3 trials demonstrated that a larger proportion of stage 3 or 4 CKD patients with SHPT and vitamin D insufficiency achieved ≥30% reductions in plasma intact parathyroid hormone (iPTH) when treated with Rayaldee than with placebo. Vitamin D insufficiency was corrected in more than 80% of the patients receiving Rayaldee compared with less than 7% of subjects receiving placebo. Mean serum calcium and phosphorus levels increased by 0.1 mg/dL during Rayaldee treatment compared to placebo treatment, but these changes were deemed clinically irrelevant. No differences in Rayaldee's efficacy or safety were observed between patients with stage 3 CKD or stage 4 CKD.

"Rayaldee fills a large void in the current treatment options for SHPT in predialysis patients," commented Dr. Charles W. Bishop, CEO of OPKO's Renal Division. "The current standard of care is high dose vitamin D supplementation, an approach for treating SHPT that is neither FDA approved nor demonstrated to be safe and effective in this population. SHPT is a progressive disease that becomes increasingly debilitating and difficult to treat, necessitating timely and effective treatment."

"Rayaldee is an important new option for treating SHPT in patients with stage 3 or 4 CKD and vitamin D insufficiency," stated Kevin J. Martin, Director of Research, Division of Nephrology at Saint Louis University School of Medicine. "The great majority of SHPT cases in this patient population are associated with vitamin D insufficiency, a problem that Rayaldee can correct."

About Rayaldee

Rayaldee (calcifediol) extended release capsules are approved by the U.S. Food and Drug Administration (FDA) for the treatment of SHPT in adult patients with stage 3 or 4 CKD and serum total 25-hydroxyvitamin D levels less than 30 ng/mL. Rayaldee has a patented formulation designed to raise serum total 25-hydroxyvitamin D (prohormone) concentrations to targeted levels (at least 30 ng/mL) and to reduce elevated iPTH. OPKO expects to launch Rayaldee in the U.S. through its dedicated renal sales force in the second half of 2016. Rayaldee is not indicated in patients with stage 5 chronic kidney disease or end-stage renal disease on dialysis. The full prescribing information for Rayaldee will be available at www.opkorenal.com.

Potential side effects of Rayaldee include hypercalcemia (elevated serum calcium), which can also lead to digitalis toxicity, and adynamic bone disease with subsequent increased risk of fractures if intact PTH levels are suppressed by Rayaldee to abnormally low levels. Severe hypercalcemia may require emergency attention; symptoms of hypercalcemia may include feeling tired, difficulty thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst, increased urination, and weight loss. Digitalis toxicity can be potentiated by hypercalcemia of any cause. Excessive administration of Rayaldee can cause hypercalciuria, hypercalcemia, hyperphosphatemia, or oversuppression of intact PTH. Common symptoms of vitamin D overdosage may include constipation, decreased appetite, dehydration, fatigue, irritability, muscle weakness, or vomiting. Patients concomitantly taking cytochrome P450 inhibitors, thiazides, cholestyramine, phenobarbital or other anticonvulsants may require dose adjustments and more frequent monitoring.

The most common adverse reactions in clinical trials (≥3% and more frequent than placebo) were anemia, nasopharyngitis, increased blood creatinine, dyspnea, cough, congestive heart failure and constipation.

Savient announces results from KRYSTEXXA Phase III trials on gout-related kidney disease

Post-hoc analysis evaluated more than 200 patients with CKD stages one through four (n=34, 74, 80, 23, respectively) who were randomized to receive treatment with KRYSTEXXA (pegloticase, see structure) 8 mg every other week, 8 mg every four weeks or placebo. Baseline CKD stage was similar across treatment arms, and there was no significant difference in rates of response to KRYSTEXXA by CKD stage (p<0.311). Additionally, treatment with KRYSTEXXA did not impact estimated GFR levels in patients with or without CKD. Similar results were seen in a 24-month open-label extension study.                 

In another study presented as a poster at EULAR, 35 percent of patients diagnosed with gout in Western Europe reported experiencing pain in the last 30 days (versus 20 percent in the control group of those who did not report gout; p<0.05).  Of those patients, 23 percent reported severe daily pain (versus 13.5 percent in control group; p<0.05), which impacted quality of life as assessed by the SF-12 health outcome measurement tool.  Based on study data, it is estimated that one in five gout patients in Western Europe experiences moderate to severe daily pain, one of the symptoms of gout.

Ref : http://investor.savient.com/releasedetail.cfm?ReleaseID=680494

Savient announces results from KRYSTEXXA Phase III trials on gout-related kidney disease: Savient Pharmaceuticals, Inc. announced new data presented in an oral session at the European League Against Rheumatism (EULAR) 2012 congress showed that patients with refractory chronic gout (RCG) who also suffer from chronic kidney disease (CKD) responded to treatment with KRYSTEXXA (pegloticase) regardless of baseline CKD stage.