공시 • Apr 30
Dimerix Limited Announces Completion of Blinded Assessment of ACTION3 Statistical Assumptions
Dimerix Limited announced that the blinded review of ACTION3 Phase 3 study data to confirm statistical assumptions of the primary endpoint has been successfully completed. This blinded review confirms that the ACTION3 study remains appropriately statistically powered to detect the treatment effect for the proteinuria primary endpoint. Having the ACTION3 Phase 3 study with >90% statistical power for its primary endpoint means that if DMX-200 continues to reduce proteinuria in trial patients as anticipated, then there is a >90% chance that the study will successfully show a statistically significant proteinuria treatment effect at the trial's conclusion. An external statistical blinded review of ACTION3 data has achieved its objective by confirming that the study remains appropriately statistically powered (>90%) to demonstrate a treatment effect for the primary study endpoint of proteinuria; meaning that if DMX-200 continues to reduce proteinuria in trial patients as anticipated, then there is a >90% chance that the study will successfully show a statistically significant proteinuria treatment effect at the trial's conclusion. To maximise the likelihood of a successful study outcome and regulatory success, Dimerix and its commercialisation partners will continue the ACTION3 Phase 3 Study to the final proteinuria endpoint. As previously announced, the FDA has agreed that proteinuria is an appropriate endpoint for full regulatory approval for DMX-200 in ACTION3. Evidence from the PARASOL working group, together with the recent FDA approval of an FSGS therapy in the US based on the proteinuria endpoint, further supports proteinuria as the primary study endpoint for ACTION3. The Company remains well positioned to continue focussing on advancing the ACTION3 Phase 3 clinical trial, as well as the advanced licensing discussions with potential partners in territories not already licensed. The ACTION3 Phase 3 clinical trial adult cohort is fully recruited, with 333 patients; the last patient is expected to receive their last dose in March 2028. Recruitment of pediatric patients aged 12-17 years old remains ongoing as an independent cohort in the trial, and if successful, may allow Dimerix to expand its application for DMX-200 to adolescents in key territories. As previously reported, the ACTION3 Phase 3 study passed a formal futility analysis of the proteinuria endpoint in March 2024 demonstrating the drug was performing better than placebo at that point in time; and a further 7 Independent Data Monitoring Committee (IDMC) reviews to date have not identified safety issues or requested changes to the protocol. In parallel to the blinded review, Dimerix and its commercial partners assessed the changes to the Focal Segmental Glomerulosclerosis (FSGS) landscape and potential endpoints since initiation of the ACTION3 study in 2022, all of which support proteinuria as the primary endpoint. Specifically, the PARASOL working group outcomes provided evidence of proteinuria as a candidate surrogate endpoint for FSGS; FDA provided positive feedback to Dimerix confirming that the proteinuria endpoint is appropriate for the full approval of DMX-200; and, earlier this month, FDA approved a new treatment for FSGS based on proteinuria as an endpoint. A key finding from PARASOL working group analysis was that proteinuria required smaller sample sizes and demonstrated less variability than eGFR for FSGS clinical trials and could therefore reduce risk for potential downstream marketing approval in the US. Collectively, the PARASOL working group analysis, the National Registry of Rare Kidney Diseases UK (RaDaR) analyses, Kaiser Permanente analyses, third party FSGS study data, and FSGS key opinion leaders all suggest that measuring proteinuria change from baseline is a far more statistically achievable endpoint for DMX-200 than eGFR endpoints and may substantially reduce the risk for traditional approval. Given that any application for accelerated approval based on proteinuria would likely require that the ACTION3 use an eGFR-based confirmatory endpoint, which would increase costs, lengthen study timeline and necessitate the splitting of alpha, potentially reducing the probability of success for the final endpoint, Dimerix and its commercial partners have concluded that conducting an interim analysis required for an Accelerated Approval application would not now be the most strategic and optimal course for the trial. The FDA has previously confirmed that the proposed primary endpoint of percent reduction in proteinuria compared to placebo is suitable to support traditional approval of DMX-200 via the 505(b)(1) pathway, should the findings of the ACTION3 be positive, with change in eGFR as a secondary endpoint. Given the successful blinded interim futility analysis in 2024, the company know that DMX-200 was performing better than placebo in reducing proteinuria at that point in time, and with seven independent data monitoring committee reviews completed, the company is confident that DMX-200 is well tolerated. The outcome of this review and the decision to proceed to completion of ACTION3 to support traditional approval helps strengthen the probability of ACTION3 success and ultimately deliver a potential new therapy for patients with FSGS while also reducing risk and adding value for Dimerix shareholders and partners. The ACTION3 Phase 3 study is a pivotal Phase 3, multi-centre, randomised, double-blind, placebo-controlled study of the efficacy and safety of DMX-200 in patients with FSGS who are receiving a stable dose of a blood pressure medication known as an angiotensin II receptor blocker (ARB). Once the ARB dose is stable, patients are then randomised to receive either DMX-200 (120 mg capsule, twice daily) or placebo for a 2-year treatment period. The single Phase 3 trial in FSGS patients is designed to capture evidence of proteinuria reduction and kidney function (eGFR slope) during the trial, aimed at generating sufficient evidence to support marketing approval.
