Dimerix Limited (ASX: DXB) shares have rallied over 36% as the company reported positive safety and efficacy data following its now completed 27 patient Phase 2a proof of concept, dose escalation study in chronic kidney disease (CKD) for lead program, DMX-200.
- DMX-200 Phase 2a clinical trial meets primary safety endpoint and demonstrates encouraging efficacy in a clinically meaningful number of patients.
- 25% of patients achieved a greater than 50% reduction in proteinuria, beyond that achieved with the highest dosage of current standard of care therapy.
- 45% of patients granted ability to continue ongoing treatment under Special Access Scheme upon recommendation of their advising physician, confirming confidence in the treatment.
- Study data informs dosing and patient targeting parameters to progress the DMX-200 Phase 2b efficacy study in 2017
Dimerix will now progress with the design for the planned Phase 2b DMX-200 study.
The primary endpoint of the Phase 2a study – demonstrating safety and tolerability – has been met. In addition, encouraging efficacy signals have been demonstrated, with 25% of patients showing a reduction in excess protein in the urine (proteinuria) of over 50%, beyond that achieved with the highest dosage of current standard of care therapy (irbesartan.).
Associate Professor David Packham, one of the Principal Investigators in the study and Director of the Melbourne Renal Research Group, said “These are very encouraging data. DMX-200, and its combination with existing best therapy, appears safe and was well tolerated. An incremental 50% fall in proteinuria is a ‘high bar’ to set in studies of this type and the observation of this efficacy endpoint in 25% of the patients certainly warrants further clinical investigation in a larger, more targeted, population.’
DMX-200 Phase 2a trial overview
DMX-200 is an adjunct therapy program for Chronic Kidney Disease (CKD) involving patients stably treated with irbesartan (current standard of care) and additionally treating them with propagermanium. The Phase 2a trial enrolled 27 patients in an open label trial, with patients being recruited at four sites in Australia.
The primary endpoint was the safety and tolerability of the CCR2 antagonist, propagermanium, over a wide variety of dose ranges when added to stable treatment of the Angiotensin Receptor Type 1 (AT1R) antagonist, irbesartan, in patients with proteinuria.
The secondary endpoint was the effect of propagermanium on various biomarkers, including proteinuria.
All patients were on a stable dose of irbesartan for three or more months prior to enrolment, and throughout the study.
Patients received escalating doses of propagermanium (10, 20, 30, 50, 80 mg three times per day) at four-week intervals unless proteinuria fell to within normal limits. Participants remained on their maximum dose for a further 8 weeks. Proteinuria was re-quantified 4 weeks after discontinuation of propagermanium. The patients were aged between 36 and 87 years. Primary diagnoses included diabetic nephropathy, IgA nephropathy, and other proteinuric diseases.
Top line results
Results showed no serious safety concerns were observed in patients on irbesartan when treated with 10-80 mg of propagermanium three times daily. Consistent with the nature of the patient population, three patients withdrew from the study for the following reasons: emergence of anaemia secondary to a gastrointestinal bleed, depression and progression of renal disease. Of the 24 patients that completed dosing, 6 (25%) achieved greater than 50% reduction in proteinuria during at least one dose level of propagermanium.
Full data will be released in a key scientific forum in due course.
Special Access Scheme
Upon the recommendation of their physician, 11 (45.8%) of the patients who completed the study applied for and were accepted into the Australian Therapeutic Goods Administration’s Special Access Scheme to enable continued access to the drug after completion of the study. This result demonstrates the physicians’ confidence that DMX-200 was having a positive effect on their patients. The physicians’ recommendation was based on patients meeting one or more of the following criteria:
Patients were either classified as a responder as defined above, or;
A reduction in proteinuria was observed, which the physician considered encouraging, or;
A 50% or greater increase in proteinuria in the follow-up period which occurred after last dose, suggesting that DMX-200 may have had a possible benefit in slowing the disease progression in these patients.
Preparations are underway to design the Phase 2b efficacy study for DMX-200. Using the inputs from this Phase 2a study, Dimerix will now finalise design of the patient inclusion criteria, dosing and timetable, which is expected to start by the end of 2017.
Dimerix CEO Kathy Harrison said:
“We are delighted that this study has resulted in such positive outcomes. The clinically meaningful reductions in proteinuria are highly encouraging and support the rationale behind the program. Given this is a “hard to treat” patient group, we now have a very strong indication that the treatment is having a significant impact in slowing the progression of Chronic Kidney Disease.
CKD is a complex disease and a silent epidemic. Driven by factors like increasing incidence of diabetes, it now affects 1.7 million Australians and 26 million Americans each year” she said. “It is a progressive disease, which means that without treatment, a patient’s proteinuria levels will tend to get worse over time. If we can further demonstrate in our studies that DMX-200 reduces those levels and prevents progression to the need for blood dialysis, we will have a very viable therapy and a huge leap forward in treatment options for patients over the current highest standard of care.”
Dimerix shares closed on Friday up at 1.5c per share, with 32 million shares traded for the session.