● TMX-049 Results Show
Beneficial Decrease of Urinary Albumin in T2DN ●
CALGARY, Alberta, Sept. 19, 2019 (GLOBE NEWSWIRE) --
XORTX Therapeutics Inc. ("XORTX"
or the “Company”)
(CSE: XRX; OTCQB: XRTXF), a biopharmaceutical company
focused on developing innovative therapies to treat
progressive kidney disease is pleased to share, in
conjunction with Teijin Pharma Limited (“Teijin”), the
positive, statistically significant results from a
recently completed U.S. phase 2 clinical trial
(TMX-049DN-201) in individuals with type 2 diabetic
nephropathy. This study achieved the primary endpoint
for the efficacy of this study and TMX-049 was well
tolerated. The study was entitled – “A Randomized,
Placebo-Controlled, Double-Blind, Multicenter, Phase 2
Study to Assess Safety, Tolerability, and Renal Effects
of TMX-049 in Subjects with Type 2 Diabetes and
Albuminuria”. This study was designed to test
whether the inhibition of XO using TMX-049 over a 12
week treatment period, would decrease uric acid levels,
and would provide a safe and effective therapeutic
approach to decreasing albuminuria.
Dr. Allen Davidoff stated, “In the opinion of XORTX,
TMX-049 is the leading next generation candidate
xanthine oxidase inhibitor with a desirable combination
of strong clinical safety record and potent uric acid
lowering capability. The opportunity to co-develop
TMX-049 for type 2 diabetic nephropathy, with Teijin,
and the results of this study, substantially increase
the probability of advancing a first in class and best
in class drug to slow and reverse progression of kidney
disease in individuals with type 2 diabetic nephropathy.
We are very encouraged by the solid safety record in
this trial and this outstanding positive result and look
forward to furthering the development of this
molecule.”
In healthy individuals, Albumin is a type of protein
that is normally found in the blood, but not in urine.
When Albumin protein is found in urine it is called
“albuminuria” or “proteinuria” and is interpreted by
physicians as a sign of kidney disease. One of the
primary functions of kidneys is to filter blood to
remove metabolic/ waste products and manage/balance the
excretion of water in the circulatory system. If kidneys
are damaged, protein can leak out of the kidneys and
into the urine, appearing as albuminuria. A urine
albumin level that stays the same or decreases may mean
that treatments are working, while increasing
albuminuria is a sign of worsening kidney health.
Approximately 35-40% of patients with type 1 or type 2
diabetes mellitus develop diabetic kidney disease. This
is a clinical syndrome characterized in its early stages
by persistent protienuria, then followed by a
relentless, decline in glomerular filtration rate (GFR).
One of the first clinical signs of kidney disease is
moderately increased urine albumin. If untreated,
albuminuria will gradually worsen and untreated
microalbuminuria will gradually worsen, reaching
clinical proteinuria or severely increased albuminuria
(albuminuria grade A3) over five to 15 years.
Importantly, proteinuria of increasing severity is
associated with a faster rate of renal decline,
regardless of baseline eGFR.1 As
GFR then begins to decline and, without treatment,
end-stage renal failure is likely to result in five to
seven years.2
Diabetic kidney disease is a
progressive chronic kidney disease that develops with
diabetes and is reported to be the most common cause of
dialysis. When chronic kidney disease progresses and
dialysis is initiated, not only does the patient's
quality of life significantly deteriorate, but the
social burden of medical care costs increases. There is
a rapidly growing need for treatments that improve, slow
or reverse chronic kidney disease, including diabetic
kidney disease, and that suppress the introduction of
dialysis.
TMX-049 is a novel non-purine type xanthine oxidase
inhibitor discovered by Teijin and currently under an
exclusive negotiation of co-development agreement with
XORTX as outlined in the letter of intent announced by
XORTX on March 12, 2019. TMX-049 can inhibit uric acid
production strongly by selectively inhibiting the
enzyme, xanthine oxidase.
Study TMX-049DN-201 was a randomized, double-blind,
placebo-controlled study in subjects with type 2
diabetes and albuminuria. The objective of the study was
to assess the efficacy and safety of TMX-049
administered once daily for 12 weeks. Change in
log-transformed urinary albumin-to-creatinine ratio was
set as the primary outcome measure.
Highlights of the results of this study showed that in
patients with T2DN:
- TMX-049 could be
safely administered to individuals with T2DN in the
tested dose range and was well tolerated;
- Oral daily doses
of TMX-049 could substantially and significantly
decrease serum uric acid (SUA).
- Oral daily doses
of TMX-049 decrease Urinary Albumin (UA) proteinuria
to a substantial and statistically significant
degree.
As a result, TMX-049 showed a statistically significant
improvement compared to the placebo group, achieving the
primary endpoint. No new concerns about the safety were
observed. Details of the study design can be found at: https://clinicaltrials.gov/ct2/show/NCT03449199?term=TMX-049&cond=type+2+diabetic+nephropathy&rank=1
References:
- Turin T C,
Protienuria and Rate or change in Kidney Function,
J. Am. Soc Nephrol Oct; 24(10):1661, 2013
- Persson F., and
Rossing P., Diagnosis of diabetic kidney disease:
state of the art and future perspective, Kid Int
Suppl v.8(1):2-7, 2018
About XORTX Therapeutics Inc.
XORTX Therapeutics Inc. is a biopharmaceutical company
focused on developing innovative therapies to treat
progressive kidney disease. XORTX has two lead
programs to develop treatments for progressive kidney
disease due to diabetes, diabetic nephropathy and
polycystic kidney disease. XORTX’s
XRx-008 (a proprietary reformulation of Oxypurinol) is a
late stage drug development program to treat autosomal
dominant polycystic kidney disease (ADPKD). TMX-049,
is a late phase 2b stage program in treat type 2
diabetic nephropathy (T2DN), under a Letter of Intent,
that proposes a co-development agreement with Japan’s
Teijin Pharma Limited. Secondary programs focus on
developing therapies for health consequences that
accompany pre-diabetes, diabetes and cardiovascular
disease. Additional information on XORTX Therapeutics is
available at www.xortx.com.
For further information, please contact:
Allen Davidoff, CEO - adavidoff@xortx.com or
+1 403 455 7727
or Erik Matthews, Corporate Communications - erik@xortx.com or
+1 747 203 5240
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