14 September 2020
In what has been a steadily positive research progression so far, Melbourne-based clinical-stage biopharmaceutical company Dimerix has reported a continuation of strong clinical trial results for its drug candidate DMX-200, which is aimed at a range of kidney diseases – specifically, to disrupt the mechanisms by which chronic kidney disease progresses.
The latest result is from a Phase 2 clinical trial in 40 individuals with diabetic kidney disease (DKD), evaluating the safety and efficacy of DMX-200 who were receiving a stable dose of the standard-of-care therapeutic, irbesartan.
DMX-200 is aimed at reducing the levels of proteins in the urine, which is a signs of kidney damage: albuminuria means that the patient has too much albumin (a specific blood protein) in urine.
The primary endpoint was the percent change in albuminuria from baseline after 12 weeks of treatment with DMX-200 as compared to placebo. Although a statistically significant difference in reduction of albuminuria for the primary endpoint was not seen, subsequent analysis showed statistically and clinically significant variation in treatment response for 26 patients with higher levels of albuminuria at study baseline.
In the trial, 64% of DKD patients with higher starting proteinuria levels demonstrated a clinically significant reduction in their albuminuria when receiving DMX-200 compared to placebo.
These results are consistent with previous studies of DMX-200 in chronic kidney disease (CKD) and focal segmental glomerulosclerosis (FSGS), where patients with starting high levels of albuminuria experienced clinically significant reductions in their albuminuria.
As with our previous studies, these data suggest that DMX-200 does provide benefit to patients that have progressed in kidney disease severity, and thus have a higher inflammatory response within the kidney. This is also consistent with the proposed mechanism of action of DMX-200, in which patients with higher baseline levels of proteinuria (and thus, higher levels of inflammatory response), responded to treatment with larger magnitudes than those with lower initial levels of these inflammatory drivers.
Lessening these inflammatory responses means that DMX-200 has high potential to delay the onset of end-stage kidney failure.
The results add to the body of evidence that Dimerix is accumulating that shows that the drug can be effective against kidney conditions that represent large global unmet needs.
In particular, the trial results build on those reported in July from the clinical trial of DMX-200 against FSGS.
FSGS is caused by scarring in the kidney, which can cause kidney damage and failure. The disease attacks the tiny filtering units inside a person’s kidney where blood is cleaned, known as glomeruli. FSGS can lead to permanent kidney damage and kidney failure in children and adults.
There are no treatments on the market today, and FSGS is a particularly heart-breaking disease: studies show that half of all children who acquire the condition will endure kidney failure within five years. DMX-200 has the potential to be the first ever treatment for FSGS, which is a multi-billion-dollar market in the US alone.
Because of this, Dimerix has received Orphan Drug Designation for DMX-200 in both the US and Europe for FSGS. This is a special status granted to a drug to treat a rare disease or condition. In Australia, Dimerix supplies DMX-200 to patients through “compassionate use,” as part of the Therapeutic Goods Administration (TGA) Special Access Scheme, or SAS.
It is a similar situation with DKD, but with a far larger and sadly growing population. There were 23 million diagnosed diabetics in the US alone in 2017, and the incidence of diabetes is estimated to grow by 54% by the year 2040. Approximately 40% of all diabetics suffer from kidney disease, which is a progressive disease leading to kidney failure and dialysis – and many of them do not know it yet. There is no cure for diabetic kidney disease, and current treatment options are ineffective as the kidneys deteriorate towards failure.
In March, Dimerix announced that the patients from its DKD phase 2 trial would also continue their treatment with DMX-200 under the compassionate use provisions of the TGA’s SAS.
“This is now the third study completed by Dimerix that shows efficacy in a group of patients with active inflammatory disease, and supports our plan to progress DMX-200 into a Phase 3 clinical study in FSGS in the first half of 2021,” said Dr Nina Webster, CEO and Managing Director of Dimerix. “We’ll do this in parallel to partnering discussions, and ultimately, further testing in later-stage diabetic kidney disease patients.”
“The collective Phase 2 data is invaluable in informing the design and execution of our single Phase 3 study in FSGS, and further increases our confidence that DMX-200 will prove a valuable therapeutic option to patients suffering FSGS and who currently have no approved or effective medication,” Webster said.
In addition to the DKD and FSGS renal programs, Dimerix continues to work on a study in patients with Acute Respiratory Distress Syndrome (ARDS), which is a major cause of death associated with COVID‑19, and its DMX-700 therapeutic candidate in chronic obstructive pulmonary disease (COPD).
In June, Dimerix announced that DMX-200 will be used in a global trial to treat patients with ARDS. The drug, was chosen as part of the Randomised, Embedded, Multifactorial Adaptive Platform trial for Community-Acquired Pneumonia (REMAP-CAP) program, which is endorsed by the World Health Organisation (WHO). The REMAP-CAP trials have been established by a group of intensive care specialists worldwide, to enable researchers to rapidly analyse the effectiveness of multiple different treatment options for eligible COVID-19 patients admitted to ICU. The ultimate aim of the REMAP-CAP trials is to future-proof for pandemics like COVID-19.
“The mechanism of increased treatment effect at higher levels of inflammatory disease burden, which DMX-200 has shown in its DKD and FSGS trials, is also consistent with the drug’s planned use for the treatment of ARDS caused by COVID‑19, where high concentration of MCP-1 in lung fluid is correlated with poor patient outcomes and where DMX-200 may have the maximum effect,” said Dr Webster.
“Dimerix is uniquely positioned to support the global effort in identifying COVID-19 treatments, as well as having two Phase 2 renal clinical studies feeding into a Phase 3 clinical study next year.”
Tel: +61 (0)3 9620 3333
Dr Nina Webster, Dimerix Limited
Chief Executive Officer & Managing Director
Tel: +61 1300 813 321