Five of the 6 patient responder sub-group (83%) had a primary diagnosis of diabetic nephropathy and 1 of the 6 responders (17%) had a primary diagnosis of IgA nephropathy.
• Detailed data from Dimerix’s DMX-200 Phase 2a trial in Chronic Kidney Disease (CKD) presented at American Society of Nephrology’s (ASN) Annual Kidney Week conference in New Orleans this week
• Post hoc, detailed data analysis shows efficacy signals in diabetic nephropathy and IgA nephropathy sub-groups
• Five of the six (83%) identified responders had a primary diagnosis of diabetic nephropathy
• Average Albumin Creatinine Ratio (ACR) reduction of 35.6% (p=0.0063) (above standard of care) was observed in the diabetic nephropathy sub-group, an exceptional result for this indication
• Diabetic nephropathy is the single most common cause of chronic kidney disease worldwide, affecting 3% of the population. The findings from this study have the potential to substantially broaden licensing opportunities for DMX-200
• DMX-200 Phase 2a data has been used as the basis for the filing of two provisional patent applications.
MELBOURNE, Australia, 2nd November 2017: Dimerix Limited (ASX: DXB), a clinical stage biotechnology company today announced in-depth, sub-group data from its recently completed DMX-200 Phase 2a trial in Chronic Kidney Disease (CKD) to be delivered at the American Society of Nephrology’s (ASN) Annual Kidney Week conference in New Orleans.
The Phase 2a dose escalation study of DMX-200, Dimerix’s lead program, examined 27 patients with CKD. 24 patients completed the study, and 3 of the 27 did not complete for reasons unrelated to the study. Top line data, announced in July, showed that DMX-200 met its primary safety endpoint with encouraging, clinically meaningful efficacy data. Six of the 24 patients (25%) to complete the study met the pre-specified criteria of ‘responder’ as defined by reduction of proteinuria to normal levels, or a 50% reduction in proteinuria, over that being achieved with the current standard of care.
The new data are based on a post hoc detailed analysis of individual patients by sub-group. Five of the 6 patient responder sub-group (83%) had a primary diagnosis of diabetic nephropathy and 1 of the 6 responders (17%) had a primary diagnosis of IgA nephropathy. This indicates particularly compelling efficacy signals for the diabetic nephropathy sub-group. The IgA subgroup represents patients suffering from a particularly aggressive kidney disease, and warrants further investigation.
Kathy Harrison, Dimerix CEO said: “Diabetic nephropathy represents the single most common cause of CKD worldwide, affecting an estimated 3% of the US population with a 2014 market value estimated at $US931m in the US alone. Early efficacy signals in this patient sub-group indicate a potential increase in the commercial value of DMX-200, which we expect should increase its attractiveness for out-licensing.”
Associate Professor David Packham, Director of the Melbourne Renal Research Group and one of the trial’s Principal Investigators added that “The efficacy signal among patients with Type 2 diabetic nephropathy is remarkable as it is seen on top of the maximum recommended dose of existing best therapy. Because of the unique study design, it is unlikely that consistent changes of this magnitude could be ascribed to a late effect of standard therapy or could have occurred spontaneously without the administration of DMX-200”
DMX-200 Phase 2a data has been used as the basis for the filing of two new provisional patent applications describing the discovery of the optimal dose for the therapy and associated extended release formulation.
Informed by the detailed analysis, Dimerix is in the final stages of designing the protocol for a double-blind, placebo-controlled Phase 2b efficacy trial for DMX-200, which is scheduled to begin patient recruitment in Q1 Calendar 2018 throughout a number of sites in Australia.
Three patient sub-groups have been selected for the Phase 2b trial in consultation with Dimerix’s recently appointed Medical Advisory Board (MAB) consisting of respected kidney experts (nephrologists) led by Associate Professor David Packham as Chair.
The three subgroups will consist of patients with diabetic nephropathy; IgA nephropathy and Focal Segmental Glomerulosclerosis (FSGS).
Dimerix has already secured orphan drug designation in the US for DMX-200 in FSGS and has been in discussions with the US Federal Drug Administration (FDA) about filing an Investigational New Drug application in this indication, which will represent a faster route to market. This rare sub-group represents a patient population with high unmet need and will be further evaluated in the Phase 2b study.
As mentioned above, the diabetic nephropathy results are particularly compelling and represent a significant, additional licensing opportunity for Dimerix, given the massive population of Diabetic Nephropathy sufferers world-wide and few therapeutic opportunities.
The IgA nephropathy sub-group represents patients suffering from a particularly aggressive kidney disease, and the results warrant further investigation.
ASN Poster Presentation details
Poster: The poster presentation is entitled ‘A Phase 2a trial of DMX-200: synergistic blockade of AT1R and CCR2 in patients with Chronic Kidney Disease’. A copy of the poster is appended to this announcement.
Presenter: Professor David Power.
Date/time: 10am on 2nd November (New Orleans time).
Location: Ernest N. Morial Convention Centre, New Orleans, LA.
The poster is available on the Dimerix web site here: http://dimerix.com/wp-content/uploads/ASN-2017-Poster.pdf
DMX-200 Phase 2a secondary endpoint efficacy results*
The following overall and sub-group results were achieved for patients on the trial. In July 2017, with the original data release, we reported:
• 6 out of 24 patients (25%) to complete the study had achieved the pre-specified criteria of ‘responder’ as defined by achieving reduction of proteinuria to normal levels, or a 50% reduction in proteinuria (measured by the PCR ratio) Since the original data release in July, post hoc analysis has identified:
• 13 of 24 patients who completed the study (54%) achieved at least a 30% reduction in PCR
• 5 of the 6 persons originally announced responder sub-group (83%) had a primary diagnosis of diabetic nephropathy. 1 of the 6 responders (17%) had a primary diagnosis of IgA nephropathy
• 50% (5/10) of patients with a primary diagnosis of diabetic nephropathy were classified as responders
• An average Albumin Creatinine Ratio (ACR**) mean reduction of 35.6% in the Diabetic Nephropathy sub-group which was deemed statistically significant (p=0.0063)
• An average Protein Creatinine Ratio (PCR**) mean reduction of 31.9% in the Diabetic Nephropathy sub-group which was deemed statistically significant (p=0.0088). Associate Professor David Packham added “A mean reduction of proteinuria levels (measured by PCR) of 32% is not only statistically significant but also very significant clinically. Normally an intervention that reduces proteinuria or albuminuria in these patients by 15% or more is considered likely to impact on renal functional outcomes and potentially significantly delay the need for renal replacement therapies.”
* Responses are considered additional to any effect of irbesartan (existing standard of care) on proteinuria levels.
** Protein Creatinine Ratio (PCR) is a measure of proteinuria levels and is a respected indicator of CKD. An alternate measure is the Albumin Creatinine Ratio (ACR).
