Vadadustat

Vafseo is currently only approved in dialysis patients with chronic kidney disease-related anemia thanks to safety concerns raised by the FDA. Despite finally winning a hard-fought FDA approval for its chronic kidney disease (CKD) anemia drug Vafseo last year, Akebia Therapeutics’ endgame remains focused on pushing the therapy into a wider pool of patients both on and off dialysis.Now, in tandem with Vafseo’s U.S. market debut, Akebia is putting its CKD expansion plans into action.Akebia on Thursday laid out plans to kick off a phase 3 clinical trial, dubbed Valor, to assess Vafseo as a potential treatment for anemia in late-stage CKD patients who aren’t on dialysis.Vafseo, which is part of the hypoxia-inducible factor–prolyl hydroxylase inhibitor (HIF-PHI) branch of meds, was approved last March to treat CKD-associated anemia in patients who have received dialysis for at least three months.Vafseo already boasts CKD anemia approvals in both dialysis and nondialysis patients in some countries outside the U.S., but safety concerns raised by the FDA—mainly around cardiovascular risks—led to the drug receiving a more limited label in the U.S.Regarding Valor, Akebia aims to recruit roughly 1,500 U.S. patients with stage 4 or 5 CKD not on dialysis for the late-stage cardiovascular outcomes trial, according to a presentation at the J.P. Morgan Healthcare Conference in January.The company said Thursday in its 2024 annual report that it has now submitted a trial protocol to the FDA and expects to meet with the regulator to discuss its designs. If all goes to plan, Akebia hopes to start the study in the second half of 2025.As for the population Akebia is targeting, stage 4 CKD is severe and points to advanced kidney damage with a high risk to progress to kidney failure. Stage 5 of the disease describes the point at which a patient’s kidneys fail, leading to dangerous buildups up fluid, electrolytes and waste in the body.Patients with end-stage CKD need dialysis or a kidney transplant to continue living, though some choose to manage their symptoms with conservative care instead.Akebia estimates there are around 550,000 patients with stage 4 or 5 CKD who are anemic and not receiving dialysis, though the company asserts that just 25% of those patients are currently treated for anemia. The company noted in its annual report that there are well-known risks to beginning dialysis with unmanaged anemia, while use of erythropoietin stimulating agents (ESAs)—a common class of CKD anemia drug—is “low and declining in the non-dialysis patient population.”“We believe the availability of an oral HIF-PH inhibitor within the non-dialysis patient population could address the issues contributing to the decline in ESA use among that patient population,” the company said in its annual filing.Akebia additionally pointed to a recent Spherix Global Insights report that found 78% of doctors said they would increase anemia treatment for nondialysis CKD patients if an HIF-PH inhibitor were approved.  A U.S. approval bid in nondialysis patients has long been part of Akebia’s overall plan for Vafseo, with the company noting at JPM that its upcoming Valor study could unlock a "multi-billion-dollar U.S. market opportunity."Meanwhile, when the company set Vafseo’s price tag notably higher than that of GSK’s rival HIF-PHI drug Jesduvroq in July, Akebia’s CEO, John Butler, explained that the company had to account for a potential label expansion under the Inflation Reduction Act (IRA), which limits how quickly drugmakers can raise a medication’s price.“[With] the IRA now, you really can’t change your price when you get a new indication,” Butler said on an investor call last summer. “You have one opportunity to price your drug, so we really have to think about that, that expanded label, as we thought about the strategic pricing and getting outside of dialysis.”Vafseo’s path to the FDA finish line, even in the more limited dialysis patient population, was anything but easy.Akebia’s original approval bid for Vafseo in both dialysis-dependent and nondialysis patients was shot down by the FDA in March 2022, with the regulator flagging safety concerns for the drug, including higher risk of thromboembolic events and liver injury.Akebia contested those concerns and soldiered on, working through a cost-cutting initiative and layoffs as it followed an FDA dispute resolution process that finally bore fruit in May 2023, Butler told Fierce Pharma around the time of the drug’s U.S. approval.Vafseo ultimately crossed the FDA finish line last March, thanks to a resubmission to the FDA girded with additional postmarketing safety data from Japanese patients.Vafseo started shipping out to U.S. patients Jan. 9 and is expected to reel in sales of $10 million to $11 million during its first quarter on the U.S. market, Akebia said in an earnings announcement Thursday.Three of the nation’s top four dialysis organizations have placed orders for Akebia’s anemia drug, and, as of the end of February, more than 500 prescribers had written Vafseo prescriptions, the company added. Akebia delivered the Vafseo progress report as it posted $46.5 million in total fourth-quarter revenue for 2024, down from the $56.2 million haul it brought home for the period in 2023. For the entire year, Akebia generated 2024 revenue of $160.2 million, down roughly 19% compared to 2023.Most of that sum came from Akebia’s phosphate binder Auryxia, which is cleared to control serum phosphorus levels in dialysis patients and as an iron replacement for treatment of iron deficiency anemia in adult CKD patients not on dialysis. The company also generated a small sum from license agreements and collaborations.

Strong results to date of Vafseo U.S. launch; expect Vafseo Q1 2025 net product revenues of approximately $10-$11 million Cash resources and cash from operations expected to fund current operating plan for at least two years Akebia to Host Conference Call at 8:00 a.m. ET on March 13, 2025 CAMBRIDGE, Mass., March 13, 2025 (GLOBE NEWSWIRE) -- Akebia Therapeutics®, Inc. (Nasdaq: AKBA), a biopharmaceutical company with the purpose to better the lives of people impacted by kidney disease, today reported financial results for the fourth quarter and full year ended December 31, 2024 and recent business highlights. As previously announced, Vafseo® (vadadustat) shipments to customers began January 9, 2025. Akebia expects Vafseo first quarter 2025 net product revenues of approximately $10-$11 million. Commenting on the Vafseo launch, John P. Butler, Chief Executive Officer of Akebia said: “We believe Vafseo can be a new standard of care for the treatment of anemia due to chronic kidney disease (CKD). The U.S. product launch is underway and our initial execution across multiple initiatives demonstrates we are making significant early progress towards that goal for dialysis patients. We launched Vafseo with commercial supply contracts in place with dialysis organizations caring for nearly 100% of dialysis patients in the U.S., which we believe is the first time a drug with Transitional Drug Add-on Payment Adjustment (TDAPA) reimbursement has done so. We are very pleased with the early results and expect to generate Vafseo net product revenue of approximately $10-$11 million in the first quarter of 2025.” Mr. Butler continued, “We are also excited about our potential to expand the Vafseo label to the non-dialysis CKD population, and plan to take advantage of the opportunity to meet with the U.S. Food and Drug Administration to discuss the Phase 3 VALOR study protocol. We believe taking the time for this meeting can help drive our efforts to bring a new product to market to treat this underserved patient population. We expect to initiate the VALOR study in the second half of this year.” Vafseo U.S. Commercial Update: Vafseo began shipping to dialysis centers and authorized distributors on January 9, 2025 and the first prescription was written on January 13, 2025.As of today, three of the top four dialysis organizations have placed orders.Through the end of February, more than 500 prescribers have written a prescription for Vafseo and each prescriber, on average, has written approximately 8 prescriptions. Additional Key Business Updates: In December 2024, Akebia announced that U.S. Renal Care enrolled the first patients in VOICE, a collaborative clinical trial of Vafseo designed to assess mortality and hospitalization in patients treated with Vafseo compared to current standard of care. U.S. Renal Care has now enrolled more than half of the total target of 2,200 patients.Vafseo has been recommended for symptomatic anemia in adults undergoing dialysis for CKD by the United Kingdom (U.K.) National Institute for Health and Care Excellence (NICE), a distinction especially relevant for practitioners and commissioners making care choices for patients in the U.K. and of interest globally. Akebia’s partner Medice has now launched Vafseo in the U.K.Akebia plans to initiate a Phase 3 clinical trial (VALOR) to study the use of vadadustat in treating anemia in late-stage CKD patients who are not on dialysis. Akebia expects the VALOR clinical trial to begin in the second half of 2025. Financial Results Revenues: Total revenues were $46.5 million in the fourth quarter of 2024 compared to $56.2 million in the fourth quarter of 2023, and $160.2 million for the full-year 2024 compared to $194.6 million for the full-year 2023. Auryxia® (ferric citrate) net product revenues were $44.4 million in the fourth quarter of 2024 compared to $53.2 million in the fourth quarter of 2023, and $152.2 million for the full-year 2024 compared to $170.3 million for the full-year 2023. These decreases were primarily driven by a reduction in volume, partially offset by price increases and execution of our contracting strategy with third party payors.License, collaboration and other revenues were $2.1 million in the fourth quarter of 2024 compared to $3.0 million in the fourth quarter of 2023, and $8.0 million for the full-year 2024 compared to $24.3 million for the full-year 2023. License, collaboration and other revenue in the full-year 2023 included a one-time $10 million license agreement-related upfront payment. COGS: Cost of goods sold was $20.4 million in the fourth quarter of 2024 compared to $18.7 million in the fourth quarter of 2023, and $63.2 million for the full-year 2024 compared to $74.1 million for the full-year 2023. In the full-year 2024 and during the fourth quarter of 2023, we realized a $12.3 million benefit, and a $4.3 million benefit, respectively, due to our ability to sell inventory previously written down as excess inventory. In addition, the decrease in cost of goods sold in both period-over-period comparisons reflects lower Auryxia sales volumes in 2024 as compared to 2023.R&D Expenses: Research and development expenses were $11.8 million in the fourth quarter of 2024 compared to $9.9 million in the fourth quarter of 2023, and $37.7 million for the full-year 2024 compared to $63.1 million for the full-year 2023. The quarterly increase was driven by expense related to the amendment of our license agreement with Cyclerion. The yearly decrease was driven by the completion of activities related to certain clinical trials, lower headcount-related costs and decreased professional service and consulting expenses.SG&A Expenses: Selling, general and administrative expenses were $27.7 million in the fourth quarter of 2024 compared to $25.4 million in the fourth quarter of 2023, and $106.5 million for the full-year 2024 compared to $100.2 million for the full-year 2023. These increases were driven by costs incurred in connection with preparatory activities related to the Vafseo U.S. launch.Net Income / Loss: Net loss was $22.8 million in the fourth quarter of 2024 compared to net income of $0.6 million in the fourth quarter of 2023. Net loss was $69.4 million for the full-year 2024 compared to $51.9 million for the full-year 2023. The increases in net loss were impacted by lower period-over-period revenues, as well as by non-cash interest expense incurred in 2024 related to the settlement royalty liability in connection with the Vifor Termination and Settlement Agreement we signed in July 2024, which was $4.9 million in the fourth quarter of 2024 and $9.3 million for the full-year 2024.Cash Position: We expect our existing cash resources and cash from operations will be sufficient to fund our current operating plan for at least two years. Cash and cash equivalents as of December 31, 2024, were approximately $51.9 million as compared to $42.9 million as of December 31, 2023. Post year-end, we further strengthened our financial position, including through share sales under our at-the-market facility, which raised $18.4 million. In addition, on February 3, 2025, we elected to access Tranche C of the BlackRock Credit Agreement, resulting in net proceeds of $9.3 million. Conference Call Akebia will host a conference call on Thursday, March 13 at 8:00 a.m. Eastern Time to discuss fourth quarter and full year 2024 earnings. To access the call, please register by clicking on this Registration Link, and you will be provided with dial in details. To avoid delays and ensure timely connection, we encourage dialing into the conference call 15 minutes ahead of the scheduled start time. A live webcast of the conference call will be available via the “Investors” section of Akebia's website at: https://ir.akebia.com/. An online archive of the webcast can be accessed via the Investors section of Akebia's website at https://ir.akebia.com approximately two hours after the event. 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 componentsUncontrolled hypertension WARNINGS AND PRECAUTIONS Increased Risk of Death, Myocardial Infarction (MI), Stroke, Venous Thromboembolism, and Thrombosis of Vascular AccessA 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. HepatotoxicityHepatocellular 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. HypertensionWorsening 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. SeizuresSeizures 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) ErosionGastric 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 DialysisThe 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. MalignancyVAFSEO 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 commercial supply contract coverage for Vafseo with dialysis organizations and Akebia's ability to make Vafseo available to nearly 100% of patients on dialysis in the U.S.; Akebia's plans and expectations with respect to potential Vafseo label expansion to treat anemia in late-stage CKD patients who are not on dialysis, including Akebia's expectations as to the timing of a Phase 3 trial; Akebia's statements regarding meeting with the FDA to discuss its Phase 3 study protocol; Akebia’s expectation with respect to its net product revenue for the first quarter 2025; Akebia’s plans to establish Vafseo as the new standard of care for dialysis patients with anemia due to CKD and progress towards that goal; Akebia’s expectations regarding the VOICE trial; and Akebia's expectations that its existing cash resources and cash from operations will be sufficient to fund its current operating plan for at least two years. 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: the commercial availability of Vafseo; the potential demand and market potential and acceptance of, as well as coverage and reimbursement related to, Auryxia® and Vafseo, including estimates regarding the potential market opportunity; the competitive landscape for Auryxia and Vafseo, including potential generic entrants; the ability of Akebia to attract and retain qualified personnel; Akebia's ability to implement cost avoidance measures and reduce operating expenses; decisions made by health authorities, such as the FDA, with respect to regulatory filings and other interactions; the potential therapeutic benefits, safety profile, and effectiveness of Vafseo; the results of preclinical and clinical research; manufacturing, supply chain and quality matters and any recalls, write-downs, impairments or other related consequences or potential consequences; 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®, Auryxia® and Vafseo® are registered trademarks of Akebia Therapeutics, Inc. and its affiliates. Akebia Therapeutics Contact Mercedes Carrasco mcarrasco@akebia.com AKEBIA THERAPEUTICS, INC.Consolidated Statements of Operations Quarters Ended December 31, Years Ended December 31, (in thousands, except share and per share data) 2024 2023 2024 2023 Revenues: Product revenue, net$44,370 $53,233 $152,180 $170,301 License, collaboration and other revenue 2,127 2,963 8,000 24,322 Total revenues 46,497 56,196 160,180 194,623 Cost of goods sold: Cost of product and other revenue 11,355 9,656 27,135 38,107 Amortization of intangibles 9,010 9,010 36,042 36,042 Total cost of goods sold 20,365 18,666 63,177 74,149 Operating expenses: Research and development 11,787 9,866 37,652 63,079 Selling, general and administrative 27,674 25,434 106,545 100,233 License expense 978 856 3,220 3,237 Restructuring — — 58 181 Total operating expenses 40,439 36,156 147,475 166,730 Operating income (loss) (14,307) 1,374 (50,472) (46,256)Other income (expense), net (6,822) (761) (18,091) (5,145)Change in fair value of warrant liability (1,675) — (330) — Loss on extinguishment of debt — — (517) — Loss on lease termination — — — (524)Net income (loss)$(22,804) $613 $(69,410) $(51,925)Net income (loss) per share Basic and diluted$(0.10) $— $(0.33) $(0.28)Weighted-average number of common shares outstanding:Basic 218,699,008 189,903,365 210,946,658 187,465,448 Diluted 218,699,008 190,496,470 210,946,658 187,465,448 Selected Balance Sheet Data(unaudited) December 31, (in thousands) 2024 2023 Cash and cash equivalents $51,870 $42,925 Working capital $32,917 $18,279 Total assets $220,670 $241,703 Total stockholders’ (deficit) equity $(49,185) $(30,584)