8-K: Akebia Therapeutics VOICE Trial Meets Primary Endpoint

Akebia Therapeutics and U.S. Renal Care announce the VOICE trial met its primary composite endpoint, demonstrating non-inferiority and superiority of Vafseo versus standard-of-care ESA.

Summary

• Akebia Therapeutics and U.S. Renal Care (USRC) announced the results of a planned interim analysis of the Vafseo Outcomes In Center Experience (VOICE) trial.
• The trial met its predefined stopping criteria, establishing non-inferiority and superiority of the primary composite endpoint.
• The primary endpoint is a hierarchical composite of all-cause mortality and all-cause hospitalization.
• The trial enrolled 2,116 patients and was sponsored by USRC.
• The results showed a statistically significant decrease in hospitalizations with Vafseo compared to ESA (1.11 vs. 1.23 hospitalizations per patient year).
• There was no statistically significant difference in mortality rates between Vafseo and ESA (8.77% vs. 8.78% per 100 patient-years).
• The trial was stopped early based on the recommendation of the Independent Data Monitoring Committee and Trial Steering Committee.
• Vafseo (vadadustat) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved for anemia due to chronic kidney disease in adults on dialysis.

Sentiment

Score: 7

Explanation: StockSavvy.ai views this as a positive development due to the trial meeting its primary endpoint and demonstrating a significant reduction in hospitalizations, although the lack of difference in mortality and the existing safety warnings temper the overall score.

Positives

• The VOICE trial met its primary composite endpoint with a win odds of 1.16 (p=0.0016), establishing non-inferiority and superiority.
• A statistically significant decrease in hospitalizations was observed with Vafseo compared to ESA (incidence rate ratio of 0.90).
• The trial was stopped early due to meeting prespecified stopping criteria, indicating a clear positive outcome.
• The results are described as replicating safety outcomes reported in the INNO2VATE clinical trial program.
• The American Association of Kidney Patients (AAKP) views advancements that improve outcomes and reduce hospitalizations positively for patients.

Negatives

• There was no statistically significant difference in mortality rates between Vafseo and ESA (incidence rate ratio of 1.00).
• The prescribing information for Vafseo includes a boxed warning about increased risks of death, myocardial infarction, stroke, venous thromboembolism, and thrombosis of vascular access.
• Vafseo has not been shown to improve quality of life, fatigue, or patient well-being.
• Vafseo is not indicated for patients with anemia due to CKD not on dialysis.
• Hepatotoxicity, hypertension, seizures, and GI erosion are listed as potential adverse reactions.

Risks

• The boxed warning for Vafseo highlights an increased risk of death, myocardial infarction, stroke, venous thromboembolism, and thrombosis of vascular access.
• Targeting a hemoglobin level greater than 11 g/dL is expected to further increase the risk of death and thrombotic events.
• Hepatotoxicity, including severe cases, has been reported.
• Worsening of hypertension and cases of hypertensive crisis have been reported.
• Seizures have occurred in patients treated with Vafseo.
• Gastric or esophageal erosions, including GI bleeding, have been reported.
• The safety of Vafseo has not been established for patients with anemia due to CKD not on dialysis, and it is not recommended in this setting due to observed increased risks.
• Malignancies were observed in clinical trials, although no evidence of increased carcinogenicity was seen in animal studies.

Future Outlook

Akebia and USRC expect to submit the VOICE trial data for presentation at an upcoming scientific meeting. The company's strategy, plans, prospects, expectations, beliefs, intentions, and goals are subject to various risks and uncertainties, including the potential therapeutic benefits, safety profile, and effectiveness of Vafseo, ongoing and planned research and development activities, decisions by health authorities, market potential, and the competitive landscape.

Management Comments

• "Importantly, based on the interim data, we observed that Vafseo resulted in a statistically significant and clinically meaningful reduction in the primary composite endpoint of all-cause mortality and hospitalization, with the result driven by a reduction in hospitalization."
• "We are eager to share data that we believe shows substantial clinical benefit with clinicians and dialysis industry colleagues, and expect to submit the VOICE trial results to an upcoming scientific meeting."
• "It was striking to see results in the VOICE trial, where we used vadadustat three times weekly during hemodialysis, that were nearly identical to those reported in a post-hoc analysis of the phase 3 INNO2VATE program, where vadadustat was dosed daily at home."
• "The data analyzed in the VOICE trial confirms the observation that vadadustat, when compared to standard-of-care erythropoiesis stimulating agents, reduces the composite endpoint of death or hospitalization in patients receiving dialysis with CKD-related anemia."
• "Every advancement in kidney care should ultimately be measured by its ability to help patients live healthier, fuller lives. AAKP views kidney disease as both a healthcare issue and a workforce issue because the burden of this disease extends well beyond the clinic. When patients have access to innovations that can improve outcomes, support transplant readiness, and reduce hospitalizations, they have a greater opportunity to remain active in their families, workplaces, and communities."

Industry Context

StockSavvy.ai notes that the positive results from the VOICE trial, demonstrating improved safety outcomes for Vafseo in reducing hospitalizations, could position Akebia Therapeutics more strongly in the competitive market for anemia treatments in chronic kidney disease. The trial's focus on a composite endpoint of mortality and hospitalization, with a significant reduction in the latter, addresses key concerns for patients and healthcare providers in managing kidney disease.

Comparison to Industry Standards

• The VOICE trial results, particularly the win odds of 1.16 and incidence rate ratio of 0.90 for hospitalizations, are described as nearly identical to a post-hoc analysis of the Phase 3 INNO2VATE program, which used daily dosing of vadadustat.
• The trial compared Vafseo (vadadustat) to standard-of-care erythropoiesis-stimulating agents (ESAs), which are the established benchmark for treating anemia in CKD patients.
• The incidence rate of hospitalizations for Vafseo was 1.11 per patient year compared to 1.23 for ESA.
• The incidence rate of mortality for Vafseo was 8.77% per 100 patient-years compared to 8.78% for ESA.

Stakeholder Impact

• Shareholders: Positive impact due to successful trial results potentially enhancing Vafseo's market position and Akebia's future revenue prospects.
• Patients: Potential for improved outcomes through reduced hospitalizations, though safety warnings and lack of impact on quality of life need consideration.
• Healthcare Providers: Provides data supporting the use of Vafseo for anemia in dialysis patients, particularly regarding hospitalization reduction.
• U.S. Renal Care: Positive outcome as a sponsor of the trial, reinforcing their commitment to innovation in kidney care.

Next Steps

• Akebia and USRC expect to submit data from the VOICE trial for presentation at an upcoming scientific meeting.
• The company will continue to navigate regulatory and market dynamics for Vafseo.

Key Dates

Recommendation

While the VOICE trial met its primary endpoint and showed a significant reduction in hospitalizations, the lack of a mortality benefit and the existing boxed warning for Vafseo regarding serious thrombotic events and increased mortality risk warrant a cautious 'hold' recommendation. Investors should monitor further data presentations and market adoption, considering the competitive landscape and the drug's safety profile.

Keywords

Vafseo, vadadustat, VOICE trial, anemia, chronic kidney disease, CKD, dialysis, erythropoiesis stimulating agent, ESA, clinical trial, interim analysis, Akebia Therapeutics, U.S. Renal Care, USRC, cardiovascular events, hospitalization, mortality