Dimerix Limited’s (ASX: DXB) ACTION Phase 3 trial of DMX-200 in patients with focal segmental glomerulosclerosis (FSGS) was successful in the pre-specified interim analysis of the proteinuria (efficacy) endpoint from the trial’s first 72 randomised patients.
The analysis indicates that, using a statistical measure, DMX-200 is performing better than placebo in terms of reducing proteinuria (a surrogate marker of kidney disease progression) in patients with FSGS. This analysis is extremely valuable as it is based on a significantly larger cohort than the prior Dimerix Phase 2 study which was conducted in eight patients.
An interim analysis incorporating a futility assessment (where certain data are assessed early to determine whether or not the drug is having a desired effect) is included to ensure a trial does not continue unnecessarily if there is no efficacy signal. Therefore passing this first interim analysis (a futility assessment) is important as it suggests that it is possible DMX-200 may achieve a statistically significant and clinically meaningful result at the end of the study.
ACTION3 Phase 3 clinical trial continues as planned
After notifying the company of the interim analysis results, the trial’s Independent Data Monitoring Committee (IDMC) additionally stated that it had no safety concerns relating to DMX-200 and formally recommended the trial continue as planned.
In line with best practice for blinded Phase 3 clinical trials, the interim analysis data are only reviewed by the unblinded IDMC members. Dimerix, the regulatory authorities including the United States Food and Drug Administration (FDA), and the trial investigators are blinded to treatment allocations, grouped safety and efficacy data for the ongoing trial and the data inputs into this interim analysis. It is expected that the full trial will enrol approximately 286 patients, with a second interim analysis planned after the first 144 patients complete approximately 35 weeks’ treatment.
“It is very pleasing to see that the Phase 3 clinical trial of DMX-200 was successful in the pre- specified interim futility analysis for efficacy in the first 72 patients. The positive signal suggests that treatment with DMX-200 may indeed result in a clinically meaningful improvement in kidney function when added to the standard of care in patients with FSGS.
With limited treatment options currently available, there remains a significant unmet need for more efficacious and durable therapies for FSGS,” said Professor Jonathan Barratt, Nephrologist, Mayer Professor of Renal Medicine: University of Leicester, Co-Chair UK Glomerulonephritis Clinical Study Group, Medical Advisory Board Member for Dimerix.
The ongoing Phase 3 is a double-blind, randomised (1:1) trial and is currently being conducted across multiple study sites in 11 countries, with the primary endpoints currently being both eGFR and proteinuria. Proteinuria (the measure of how much protein is in the urine), is used along with the estimated glomerular filtration rate (eGFR) in both the classification of kidney diseases and the effectiveness of therapies. Proteinuria can serve as an indicator of renal disease, and the degree of proteinuria correlates with disease progression. To date, the study has randomised and dosed 94 patients with FSGS.
A collaborative international effort has been established (project PARASOL) that aims to define the quantitative relationships between short-term changes in biomarkers (proteinuria and GFR) and long- term outcomes to further support the use of alternative proteinuria-based endpoints as a basis for accelerated and traditional approval in FSGS kidney disease.
Dimerix intends to support this working group once industry has been invited to participate, given these outcomes may support and/or influence the final ACTION3 endpoints and statistical analysis plan.
Dimerix has received a significant amount of partnering interest from pharma companies globally, with its first licence agreement entered into with Advanz Pharma in October 2023 for Europe, Canada, Australia and New Zealand, and valued at up to $230 million plus royalties on sales.
It has received several non-binding term sheets for other regional deals, with multiple parties currently in the data room conducting due diligence and negotiating a potential licensing agreement for various territories. Following the successful first interim analysis, Dimerix will focus on the execution of potential licensing deals for those available jurisdictions including in the US and China.
