Clinical Program

Clinical Program 2017-12-10T17:12:33+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. DMX-200 is currently in Phase 2 clinical trials in Australia in patients with CKD. The primary goal of this program is to demonstrate the safety of DMX-200 in these patients.

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 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 organic germanium 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 organic germanium 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

We are developing a new commercial formulation which will help patients manage their medication, by removing the inconvenient middle of the day dose. A pharmacokinetic study has been completed to compare the extended release formulation with the immediate release formulation. This data assists in confirming appropriate dosing for the Phase 2b studies.

FSGS

We are planning to commence a small study in FSGS patients commencing early 2018, using the extended release formulation. This study will be 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 open an IND and lead into a pivotal Phase 3 trial.

Diabetic Nephropathy

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 currently engaging with regulators, pharmaceutical companies and clinical experts to finalise the design of a powered double blind, placebo controlled efficacy study.

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