Vadadustat Alternative Dosing Study Results Published in the American Journal of Kidney Disease

Rhea-AI Summary

Akebia Therapeutics (Nasdaq: AKBA) announced the publication of FO2CUS trial results in the American Journal of Kidney Disease, evaluating Vafseo® (vadadustat) for anemia treatment in hemodialysis patients. The study compared three-times-weekly oral vadadustat dosing to long-acting ESA in 456 patients. Vafseo®, approved by FDA in March 2024 for anemia treatment in chronic kidney disease patients on dialysis, is scheduled for U.S. launch in January 2025. The study examined 600mg and 900mg vadadustat doses versus Mircera®, measuring hemoglobin changes at weeks 20-26 and 46-52.

Positive

• FDA approval received for Vafseo® in March 2024
• Commercial launch planned for January 2025
• Publication in prestigious American Journal of Kidney Disease validates research

Negative

• None.

Insights

Medical Research Analyst

The publication of vadadustat's alternative dosing study in a prestigious journal like AJKD represents an incremental scientific validation, but has immediate market impact. While the study demonstrates the drug's potential flexibility in dosing regimens (three times weekly vs. once daily), this data primarily serves to expand physician understanding rather than directly influence near-term commercial prospects.

The study's inclusion of 456 hemodialysis patients provides robust evidence for dosing options, but the approved label currently specifies once-daily administration. The January 2025 commercial launch timeline remains unchanged. The publication may support future label expansion efforts but doesn't materially affect current business trajectory.

Akebia continues to publish important results of FO₂CUS trial to further physicians' understanding of Vafseo® (vadadustat) 

CAMBRIDGE, Mass., Nov. 14, 2024 /PRNewswire/ -- 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 American Journal of Kidney Disease has published the results of FO₂CUS, an open-label study evaluating the efficacy and safety of vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, in hemodialysis patients who were converted from a long-acting erythropoiesis-stimulating agent (ESA) to three times weekly oral vadadustat dosing for the maintenance treatment of anemia.

The article titled, "Vadadustat Three Times Weekly in Patients With Anemia Due to Dialysis-Dependent CKD," is available here.

Vafseo® (vadadustat) was approved by the U.S. Food and Drug Administration in March 2024 for the treatment of anemia due to chronic kidney disease in adults who have been receiving dialysis for at least three months. Vafseo is approved for once-daily oral administration and is expected to be available in the U.S. in January 2025.

"The publication of the FO₂CUS data in the American Journal of Kidney Disease is an important milestone and demonstrates Akebia's commitment to both research and to continuing to publish findings from its Vafseo trials," said Steven K. Burke, M.D., Senior Vice President, Research & Development and Chief Medical Officer of Akebia.

FO₂CUS was an open-label, active-controlled, sponsor-blinded study that evaluated 456 hemodialysis patients who were randomized (1:1:1) into vadadustat 600mg, vadadustat 900mg, or a long-acting ESA (Mircera®) treatment arms. The primary efficacy endpoint was the mean change in hemoglobin (Hb) between baseline and the primary evaluation period (weeks 20-26). The secondary efficacy endpoint was the mean change in Hb between baseline and the secondary evaluation period (weeks 46-52). The top-line results of the FO₂CUS study are available here.

First published in 1981, the American Journal of Kidney Diseases is the official journal of the National Kidney Foundation. AJKD is recognized worldwide as a leading source of information devoted to clinical nephrology research and practice. Articles selected for publication in AJKD undergo a rigorous peer review and editorial consideration process, including statistical review where appropriate, supporting the journal's goal to communicate important new information in clinical nephrology in a way that strengthens knowledge and helps physicians to provide their patients with the highest standard of care.

About Akebia Therapeutics
Akebia Therapeutics, Inc. is a fully integrated biopharmaceutical company with the purpose to better the lives of people impacted by kidney disease. Akebia was founded in 2007 and is headquartered in Cambridge, Massachusetts. For more information, please visit our website at www.akebia.com, which does not form a part of this release.

About Vafseo® (vadadustat) tablets 
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.

INDICATION
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.

Limitations of Use

• 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.
  • In patients with anemia due to CKD not on dialysis.

IMPORTANT SAFETY INFORMATION about VAFSEO (vadadustat) tablets

WARNING: INCREASED RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS                             THROMBOEMBOLISM, and THROMBOSIS OF VASCULAR ACCESS. 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.

CONTRAINDICATIONS

• Known hypersensitivity to VAFSEO or any of its components
• Uncontrolled hypertension

WARNINGS AND PRECAUTIONS

• Increased Risk of Death, Myocardial Infarction (MI), Stroke, Venous Thromboembolism, and Thrombosis of Vascular Access
  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.
• Hepatotoxicity
  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.
• Hypertension
  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
  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.
• Gastrointestinal (GI) Erosion
  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.
• Serious Adverse Reactions in Patients with Anemia Due to CKD and Not on Dialysis
  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.
• Malignancy
  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.

ADVERSE REACTIONS

• The most common adverse reactions (occurring at ≥ 10%) were hypertension and diarrhea.

DRUG INTERACTIONS

• 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.

USE IN SPECIFIC POPULATIONS

• Pregnancy: May cause fetal harm.
• Lactation: Breastfeeding not recommended until two days after the final dose.
• Hepatic Impairment: Not recommended in patients with cirrhosis or active, acute liver disease.

Please note that this information is not comprehensive. Please click here for the Full Prescribing Information, including BOXED WARNING and Medication Guide.

Forward-Looking Statements
Statements in this press release regarding Akebia Therapeutics, Inc.'s ("Akebia's") strategy, plans, prospects, expectations, beliefs, intentions and goals are forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, as amended, and include, but are not limited to, statements regarding:  Akebia's expectations as to the timing of the market availability of Vafseo in the U.S. and Akebia's commitment to both research and to continuing to publish findings from its Vafseo trials. The terms "intend," "believe," "plan," "goal," "potential," "anticipate, "estimate," "expect," "future," "will," "continue," derivatives of these words, and similar references are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results, performance or experience may differ materially from those expressed or implied by any forward-looking statement as a result of various risks, uncertainties and other factors, including, but not limited to, risks associated with: whether Vafseo will be commercially available when expected; manufacturing, supply chain and quality matters and any recalls, write-downs, impairments or other related consequences or potential consequences; the potential demand and market potential and acceptance of, as well as coverage and reimbursement related to Vafseo; the competitive landscape for Vafseo; the ability of Akebia to attract and retain qualified personnel; decisions made by health authorities, such as the FDA, with respect to regulatory filings; the potential therapeutic benefits, safety profile, and effectiveness of Vafseo; the results of preclinical and clinical research; the direct or indirect impact of the COVID-19 pandemic on the markets and communities in which Akebia and its partners, collaborators, vendors and customers operate; and early termination of any of Akebia's collaborations. Other risks and uncertainties include those identified under the heading "Risk Factors" in Akebia's Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, and other filings that Akebia may make with the U.S. Securities and Exchange Commission in the future. These forward-looking statements (except as otherwise noted) speak only as of the date of this press release, and, except as required by law, Akebia does not undertake, and specifically disclaims, any obligation to update any forward-looking statements contained in this press release.

Akebia Therapeutics® and Vafseo® are registered trademarks of Akebia Therapeutics, Inc. and its affiliates.

Akebia Therapeutics Contact
Mercedes Carrasco
mcarrasco@akebia.com

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SOURCE Akebia Therapeutics, Inc.

FAQ

When will Vafseo (AKBA) be available in the US market?

Vafseo is expected to be available in the U.S. in January 2025.

What dosing regimens were tested in the AKBA FO2CUS trial?

The FO2CUS trial tested vadadustat doses of 600mg and 900mg three times weekly, compared to a long-acting ESA (Mircera®).

When did Akebia (AKBA) receive FDA approval for Vafseo?

Vafseo received FDA approval in March 2024 for treating anemia due to chronic kidney disease in adults on dialysis for at least three months.

How many patients were involved in the AKBA FO2CUS trial?

The FO2CUS trial evaluated 456 hemodialysis patients who were randomized equally into three treatment groups.