Clinical Program

Clinical Program 2018-05-26T07:42:56+00:00

Dimerix has used its Receptor HIT technology to identify a new treatment that may transform the lives of patients with Chronic Kidney Disease (CKD). CKD is a major global health problem, and is currently a significant, underserved therapeutic area.

Our novel treatment, DMX-200, aims to meet this need and improve outcomes for people with CKD. Following successful completion of a Phase 2a study in CKD patients, DMX-200 is currently in two Phase 2 clinical trials in Australia in patients with two important sub set diseases of CKD. One trial is being conducted in patients with Focal Segmental Glomerulosclerosis (FSGS), for which DMX-200 has Orphan Drug Designation in the USA, and the other in patients with Diabetic Kidney Disease (DKD).

Chronic Kidney Disease- a significant unmet need

Chronic Kidney Disease (CKD) affects over 10% of the population, and an estimated 26 million in the US alone. This prevalence is expected to increase due to the escalating incidence of cardiovascular disease, obesity and diabetes. CKD is a pressing medical need associated with several life-threatening complications that amplify the effects of the disease and result in significantly worse outcomes for patients. As the disease progresses it can lead to end-stage renal disease (ESRD), where the kidneys fail, resulting in patients requiring dialysis or a kidney transplant.

Currently, treatments for some types of CKD (such as FSGS) can include the use of several medications which are not specifically registered for this use, including immunosuppressants and steroids. These therapies have significant toxicity profiles that may be dose limiting, and efficacy can be as low as 25%.

This clear need for a safe, effective treatment to increase the quality of life and health outcomes for people with CKD is why Dimerix has developed DMX-200, our leading drug therapy.

How DMX-200 aims to combat CKD

DMX-200 tackles CKD by adding a safe anti-inflammatory drug, propagermanium, to the standard of care treatment irbesartan.

  1. Irbesartan: an off-patent angiotensin II type I receptor blocker compound used to treat hypertension and nephropathy in Type II diabetic patients. This is the current standard of care for many patients with CKD, as it manages blood pressure and leads to a decrease in proteinuria.
  2. Propagermanium: a chemokine receptor (CCR2) blocker, which is used for the treatment for Hepatitis B in Japan.

The receptors for these two drugs co-exist in the kidney, and when used in combination, irbesartan and propagermanium work synergistically to block the signals that cause inflammation.

What’s special about DMX-200?

New use of known drugs:

Both irbesartan and propagermanium have well known safety profiles, as they have each been used safely for many years. This minimizes the safety risk of DMX-200 to patients.

Doesn’t take patients off standard of care:

DMX-200 does not require patients to stop taking irbesartan, which stabilizes their blood pressure and decreases proteinuria. Taking patients off standard of care risks potentially detrimental consequences relating to uncontrolled blood pressure. Therefore, patients get to stay on their well-known and safe blood pressure controlling drug and get the additional proteinuria benefit of DMX-200.

Attacks inflammation:

Current standard of care drugs, such as irbesartan, reduce the leakage of protein into the urine. However, the reduction of kidney function continues unless the damage caused by inflammation is controlled, leaving many treatment options ineffective. By adding the anti-inflammatory drug propagermanium to irbesartan, DMX-200 aims to combat this inflammation, preserving kidney function.

Supported by Receptor-HIT platform:

DMX-200 was identified using our Receptor-HIT platform. In our meeting with the FDA, they confirmed the relevance of heteromers to drug development, which is the basis of our Receptor-HIT platform and DMX-200.

Orphan Drug Designation for Focal Segmental Glomerulosclerosis (FSGS):

Dimerix has secured orphan drug designation for DMX-200 in FSGS in the US. Current treatment options for FSGS are limited and have significant side effects, meaning there is a desperate need for safe treatments. Through the orphan drug program, DMX-200 will be have access to a number of regulatory and financial incentives, potentially meaning shorter trials and lower costs compared to other therapies.

Clinical Trial Highlights

DMX-200 Phase 2a Results

DMX-200 Phase 2a study is now completed, meeting its primary endpoint of safety and demonstrating clinically meaningful efficacy signals. Six of the 24 patients who completed the study saw a reduction in proteinuria (measured by the protein creatinine ratio – PCR) from baseline of greater than 50%. Five of those six patients had diabetic nephropathy as their primary diagnosis. A subgroup analysis was then conducted on the ten (10) patients with a primary diagnosis of diabetic nephropathy, and the mean reduction in proteinuria from baseline was 35.6% (p=0.0063) measured by the Albumin creatinine ratio (ACR) and 31.9% (p=0.0014) measured by the protein creatinine ration (PCR).

More detailed information can be seen from the posters presented at ASN2017 and WCTD2017.

The path forward – the ACTION trials

Dimerix is now conducting two trials in our ACTION (AT1R and CCR2 Targets for Inflammatory Nephrosis) program.

ACTION for FSGS

We are undertaking a Phase 2a, Double-blind, Randomised, Crossover Study Evaluating the Safety and Efficacy of Propagermanium in Patients with Primary Focal Segmental Glomerulosclerosis (FSGS) who are receiving Irbesartan.

This study is in line with our discussions with the FDA regarding the development path for DMX-200 for the orphan indication. We will continue discussions with the FDA to ensure our plans are in alignment with their expectations to enable us to lead into a pivotal Phase 3 trial.

ACTION for Diabetic Kidney Disease (DKD

The data we saw in this sub group has been exceptionally well received within the nephrology community, and is an opportunity for us to broaden the applicability of the DMX-200 program for licensing.

We are undertaking a Phase 2b, Double-blind, Randomised, Crossover Study Evaluating the Safety and Efficacy of Propagermanium in Patients with Diabetic Kidney Disease (DKD) who are receiving Irbesartan.

Manufacturing

We expect to enter a manufacturing agreement in early 2018 to manufacture both the pharmaceutical ingredient and the extended release tablet for use in the pivotal trial.

Regulatory

We are also seeking to expand the regulatory reach of our program to include Europe, and are currently engaging with European based nephrologists, and preparing to meet with European based regulatory agencies, and file an application for Orphan Drug Designation in Europe