Announcement • Jun 12
Akebia Therapeutics Strengthens Vafseo® (vadadustat) Patent Portfolio
Akebia Therapeutics announced that a new patent has been granted and listed in the Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) and it has been notified of eligibility to extend the expiration of a composition of matter patent covering Vafseo (vadadustat). The new patent and 5-year extension eligibility strengthen Akebia’s vadadustat intellectual property portfolio, which now includes 14 patents listed in the Orange Book with expiration dates out to 2036. In March 2024, Vafseo, an oral hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitor, was approved by the U.S. Food and Drug Administration for the treatment of anemia due to chronic kidney disease in adults who have been receiving dialysis for at least three months. Vafseo has been available in the U.S. since January 2025 and there are no other oral HIF-PH inhibitors to treat anemia in the market or in development in the U.S. The newly issued patent, U.S. Patent No. 12,569,474, which expires in June 2034, relates to a once daily dosing regimen for treating anemia secondary to or associated with chronic kidney disease. Separately, a composition of matter patent covering vadadustat is eligible for patent term extension under 35 U.S.C. 156 for a period of five years, extending the patent term to mid-2032 upon issuance of the Certificate of Extension by the United States Patent and Trademark Office. Vafseo also has additional patents listed in the Orange Book with expiration dates between 2027 and 2036 and has pending applications that, if issued, could expire as late as 2042. Vafseo (vadadustat) tablets is a once-daily oral hypoxia-inducible factor prolyl hydroxylase inhibitor that activates the physiologic response to hypoxia to stimulate endogenous production of erythropoietin, increasing hemoglobin and red blood cell production to manage anemia. Vafseo is approved for use in 37 countries. VAFSEO is indicated for the treatment of anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least three months. VAFSEO has not been shown to improve quality of life, fatigue, or patient well-being. VAFSEO is not indicated for use as a substitute for red blood cell transfusions in patients who require immediate correction of anemia and in patients with anemia due to CKD not on dialysis. VAFSEO 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 and 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 VAFSEO, or dosing strategy that does not increase these risks. Use the lowest dose of VAFSEO sufficient to reduce the need for red blood cell transfusions. Known hypersensitivity to VAFSEO or any of its components and uncontrolled hypertension are contraindications. A rise in hemoglobin (Hb) levels greater than 1 g/dL over 2 weeks can increase these risks. Avoid in patients with a history of MI, cerebrovascular event, or acute coronary syndrome within the 3 months prior to starting VAFSEO. Targeting a Hb level of greater than 11 g/dL is expected to further increase the risk of death and arterial and venous thrombotic events. Use the lowest effective dose to reduce the need for red blood cell (RBC) transfusions. Adhere to dosing and Hb monitoring recommendations to avoid excessive erythropoiesis. Hepatocellular injury attributed to VAFSEO was reported in less than 1% of patients, including one severe case with jaundice. Elevated serum ALT, AST, and bilirubin levels were observed in 1.8%, 1.8%, and 0.3% of CKD patients treated with VAFSEO, respectively. Measure ALT, AST, and bilirubin before treatment and monthly for the first 6 months, then as clinically indicated. Discontinue VAFSEO if ALT or AST is persistently elevated or accompanied by elevated bilirubin. Not recommended in patients with cirrhosis or active, acute liver disease. Worsening of hypertension was reported in 14% of VAFSEO and 17% of darbepoetin alfa patients. Serious worsening of hypertension was reported in 2.7% of VAFSEO and 3% of darbepoetin alfa patients. Cases of hypertensive crisis, including hypertensive encephalopathy and seizures, have also been reported in patients receiving VAFSEO. Monitor blood pressure. Adjust anti-hypertensive therapy as needed. Seizures occurred in 1.6% of VAFSEO and 1.6% of darbepoetin alfa patients. Monitor for new-onset seizures, premonitory symptoms, or change in seizure frequency. Gastric or esophageal erosions occurred in 6.4% of VAFSEO and 5.3% of darbepoetin alfa patients. Serious GI erosions, including GI bleeding and the need for RBC transfusions, were reported in 3.4% of VAFSEO and 3.3% of darbepoetin alfa patients. Consider this risk in patients at increased risk of GI erosion. Advise patients about signs of erosions and GI bleeding and urge them to seek prompt medical care if present. The safety of VAFSEO has not been established for the treatment of anemia due to CKD in adults not on dialysis and its use is not recommended in this setting. In large clinical trials in adults with anemia of CKD who were not on dialysis, an increased risk of mortality, stroke, MI, serious acute kidney injury, serious hepatic injury, and serious GI erosions was observed in patients treated with VAFSEO compared to darbepoetin alfa. VAFSEO has not been studied and is not recommended in patients with active malignancies. Malignancies were observed in 2.2% of VAFSEO and 3.0% of darbepoetin alfa patients. No evidence of increased carcinogenicity was observed in animal studies. The most common adverse reactions (occurring at = 10%) were hypertension and diarrhea. Iron supplements and iron-containing phosphate binders: Administer VAFSEO at least 1 hour before products containing iron. Non-iron-containing phosphate binders: Administer VAFSEO at least 1 hour before or 2 hours after non-iron-containing phosphate binders. BCRP substrates: Monitor for signs of substrate adverse reactions and consider dose reduction. Statins: Monitor for statin-related adverse reactions. Limit the daily dose of simvastatin to 20 mg and rosuvastatin to 5 mg. Pregnancy: May cause fetal harm. A pregnancy exposure registry is available to monitor outcomes in women exposed to VAFSEO during pregnancy. Report pregnancies to 1-844-445-3799. Lactation: Breastfeeding not recommended until two days after the final dose. Hepatic Impairment: Not recommended in patients with cirrhosis or active, acute liver disease.
