‘A key milestone’: Dimerix ACTION3 Phase 3 trial interim results meet endpoint

Dimerix ACTION3 Phase 3 trial successfully passes first interim analysis using proteinuria efficacy endpoint
DMX-200 performing better than placebo in reducing proteinuria in patients with FSGS
The trial’s IDMC says it has no safety concerns relating to DMX-200 recommending the trial should continue as planned

Special Report: Dimerix’s long-awaited interim analysis of its ACTION3 Phase 3 trial of DMX-200 in patients with focal segmental glomerulosclerosis (FSGS) have been released, meeting its interim endpoint.

Biotech Dimerix (ASX:DXB) says the Phase 3 trial was successful in the pre-specified interim analysis of proteinuria (efficacy) endpoint from the first 72 randomised patients.

The interim analysis showed DMX-200 is currently performing better than the placebo in reducing proteinuria (using a statistical measure) in patients with FSGS in a significantly larger cohort than its prior Phase 2 trial of eight patients.

DXB says passing the early interim analysis suggests a statistically significant and clinically meaningful result in reducing proteinuria at the end of the study may be possible.

The trial’s Independent Data Monitoring Committee (IDMC) also says it has no safety concerns relating to DMX-200, adding to the drug’s growing safety profile – and formally recommended the trial continue as planned.

DXB says in line with best practice for blinded Phase 3 clinical trials, the interim analysis data is only reviewed by the unblinded IDMC members.

The regulatory authorities, including the US Food and Drug Administration (FDA), DXB personnel and the trial investigators are blinded to treatment allocations, grouped safety and efficacy data for the ongoing trial and the data inputs into the interim analysis.

Titled Angiotensin II Type 1 Receptor (AT1R) & Chemokine Receptor 2 (CCR2) targets for Inflammatory Nephrosis, or ACTION3 for short DXB’s Phase 3 trial is a multi-centre, randomised, double-blind, placebo-controlled study.

The full trial is expected to enrol ~286 patients, with a second interim analysis planned after the first 144 patients complete ~35 weeks of treatment.

The ongoing Phase 3 is a double-blind, randomised trial 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, with the degree of proteinuria correlating with disease progression.

To date, the study has randomised and dosed 94 patients with FSGS.

Great need for treatment

FSGS is a rare condition affecting the kidney’s filtering units, where blood is purified, resulting in permanent kidney damage and eventual organ failure, necessitating either dialysis or a transplant.

For those who receive a transplant, around 60% get reoccurring FSGS in the transplanted kidney, and no one knows why.

The condition affects both adults and children as young as two-years-old, and at this time, there are no drugs approved, specifically for FSGS anywhere in the world, so the treatment options and prognosis are poor.

It is estimated ~80,000 individuals in the US and ~220,000 worldwide are afflicted by FSGS, making it a substantial market opportunity estimated at billions of dollars for DXB.

DXB has secured orphan drug designation (ODD) for DMX-200 in both the US and Europe for the treatment of FSGS due to the absence of an effective therapy for this condition.

The advantages of ODD encompass a range of development incentives, including seven years of market exclusivity granted by the FDA and 10 years by the EMA if regulatory approval is obtained, exemption from specific application fees and an expedited regulatory pathway to approval.

The company has also been granted conditional approval by the FDA for the brand name QYTOVRA for DMX-200.

In 2023, DXB finalised an exclusive licensing agreement worth up to $230 million for Europe, Canada and Australia/New Zealand with multinational pharmaceutical company Advanz Pharma that includes tiered, escalating, mid-teen to twenty percentage royalties on net sales of DMX-200 if it is successfully commercialised.

DXB says it has received several non-binding term sheets for other regional deals, with multiple parties currently conducting due diligence and negotiating a potential licensing deals for various territories.

Following the successful first interim analysis, DXB says it will focus on the execution of potential licensing agreements for those available jurisdictions including in the US and China.

Interim analysis success a ‘key milestone’ for DXB

The positive Phase 3 interim analysis results pushes DXB-200 step closer to potential market approval, following 12 years of work since the drug was first identified for use in the kidney disease.

FSGS results in scarring of kidney filtering units over time (about five years) until there are not enough kidney cells left to effectively filter blood.

Accomplished nephrologist and medical advisory board member for DXB, Professor Jonathan Barratt, says it was 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,” he says.

“With limited treatment options currently available, there remains a significant unmet need for more efficacious and durable therapies for FSGS.”

DXB chief medical officer Dr David Fuller says passing this first interim analysis for DMX-200 is a “key milestone” for DXB and its FSGS program.

“It demonstrates that DMX-200 is performing better than placebo in reducing proteinuria
in a much larger cohort than our prior 8-patient Phase 2 study, and this validates our strategy and our prioritisation of this potentially valuable program in a disease where there are no FDA approved therapies,” he says.

“We now look forward to rapidly expanding this study, which will include recruiting children down to 12 years old as well as adults.”

A collaborative international effort known as project PARASOL has been established to define the quantitative relationships between short-term changes in biomarkers (proteinuria and GFR) and long-term outcomes to further support use of alternative proteinuria-based endpoints as a basis for accelerated and traditional approval in FSGS kidney disease.

DXB says it intends to support project PARASOL once industry has been invited to participate, given these outcomes may support and/or influence the final ACTION3 endpoints and statistical analysis plan.