- The first patient with type 2 diabetes mellitus (T2D) and
diabetes-related complications has been enrolled in a clinical
trial called DAPAN-DIA in Basel,
Switzerland, with Olatec's NLRP3 inhibitor, dapansutrile,
which is sponsored by Principal Investigator, Marc Donath MD
- This Phase 2 randomized study is designed to evaluate
dapansutrile's efficacy and safety in approximately 300 patients
with elevated blood glucose, systemic inflammation and at risk for
complications of diabetes, despite use of standard-of-care
anti-diabetic therapy
- DAPAN-DIA represents the first T2D clinical trial of any
selective NLRP3 inhibitor in the emerging class that will also
assess cardiometabolic and other risk factors beyond
anti-hyperglycemic effects including weight lowering efficacy in
combination with GLP-1 therapy
- The trial is being funded by a consortium that includes Olatec,
the European Union under the Horizon Europe Programme (GA No
101095433) and the Swiss Government as part of the INTERCEPT-T2D
initiative
NEW
YORK, July 11, 2024 /PRNewswire/ -- Olatec
Therapeutics, Inc. (Olatec), a leader in the emerging class of
specific NLRP3 inhibitors, announced patients with type 2 diabetes
mellitus (T2D) and diabetes-related complications (the DAPAN-DIA
Study) are being enrolled in a Phase 2 clinical trial in
Basel, Switzerland.
The DAPAN-DIA Study is a randomized, double-blind,
placebo-controlled multi-center trial of the efficacy and safety of
dapansutrile in subjects with T2D and diabetes-related
complications. Target enrollment is approximately 300 patients who,
upon entry into the trial, present with low-grade inflammation,
obesity and inadequately controlled glycemia (elevated HbA1c)
despite use of standard anti-diabetic therapy. Patients will be
treated with dapansutrile or placebo for six months. "We
expect the data from this trial, including the combination with
GLP-1 therapy, will be highly relevant for understanding the full
potential of anti-inflammatory intervention with an NLRP3 inhibitor
in this setting," shared Mustafa Noor MD, Chief Medical
Officer, Olatec Therapeutics.
The study is being conducted as an investigator-sponsored study
under Principal Investigator Marc Donath MD at the University
Hospital of Basel in Switzerland, a long-time Olatec collaborator
and advisor as well as a leading researcher-clinician in
immuno-metabolism. In addition to the Swiss sites, the trial is
intended to be expanded at medical and scientific diabetes centers
of excellence within Europe,
including: Hôpital Lariboisière, Hôpital Bichat-Claude Bernard
and Hôpital Cochin in Paris, France; German Diabetes Center,
Düsseldorf, Germany; and
University Hospital of Liège in Belgium. Funding is being provided through the
INTERCEPT-T2D initiative by the European Union under the Horizon
Europe Programme (GA No 101095433), in collaboration with the Swiss
Government and Olatec.
T2D is a chronic condition characterized by elevated levels of
glucose in blood, resulting from insulin resistance and inadequate
insulin secretion. The disease is often concurrent with
obesity and associated with a range of complications, including
cardiovascular disease, renal dysfunction, retinopathy, neuropathy,
and non-alcoholic steatohepatitis, where chronic, elevated
low-grade systemic inflammation and activation of NLRP3 and
upregulation IL-1β are observed. Unlike existing diabetic
treatments that primarily focus on glucose
lowering, dapansutrile offers a novel approach to
disease-course modification, by targeting the underlying NLRP3
inflammation pathway that is implicated in driving resistance to
insulin action in T2D, promoting body weight gain and associated
with higher cardiometabolic risks.
Dr. Donath stated that, "there is a large unmet need for
effective treatment of T2D that goes beyond glycemic control and
addresses the underlying inflammatory component of the disease and
its cardiometabolic complications. The
ground-breaking DAPAN-DIA Study has the potential for
dapansutrile to represent a significant step forward in the
management of T2D."
Olatec's Founder and CEO, Damaris
Skouras, commented: "Building on our previous data in heart
failure and gout, DAPAN-DIA Study represents a major milestone in
the development of dapansutrile in the inter-related
cardiometabolic diseases linked by chronic low-grade inflammation
due to NLRP3/IL-1 activation."
About Type 2 Diabetes
Type 2 diabetes (T2D) is a
serious, chronic condition that occurs when levels of glucose in
blood are elevated because the body cannot produce any or enough of
the hormone, insulin, or cannot effectively use the insulin it
produces. Insufficient amount of insulin, or the inability of cells
to respond to it (insulin resistance), leads to high levels of
blood glucose, which is the clinical indicator of T2D and measured
clinically as HbA1c. High blood sugar levels can cause damage
to many of the body's organs, leading to disabling and
life-threatening health complications. Life expectancy for
typical patients with T2D has been estimated to be 8 years shorter
and driven by 200% increased risk of all-cause mortality.
Approximately 70% die from atherosclerotic cardiovascular disease,
40% develop chronic kidney disease (CKD) due to diabetic
nephropathy, and almost one-third develop retinopathy. As the
prevalence of T2D increases globally, the condition and its
associated complications are generating considerable - - and
growing - -economic burden on healthcare systems and societies. In
2021, USD $966 billion in global
health expenditures were due to T2D, which represents 316% increase
over the last 15 years. There are an estimated 537 million adults
living with diabetes worldwide, with the total number predicted to
rise to 643 million by 2030 and 784 million by 2045.
(Source: IDF Atlas 2021)
About Scientific Rationale for NLRP3 in Type-2
Diabetes
Low-grade chronic inflammatory response is one mechanism leading
to the development of insulin resistance, T2D, and associated
comorbidities, including liver and kidney damage. In particular,
the NLRP3 inflammasome has been shown to play a central role in
orchestrating inflammation and immune responses as it is activated
in response to several altered metabolic signals in T2D, leading
not only to the activation of caspase-1 and production of IL-1β,
but also to insulin resistance and pancreatic β cell failure.
Furthermore, activation of the NLRP3 inflammasome has been
shown to promote vascular inflammation, endothelial dysfunction,
and plaque destabilization, contributing to the pathogenesis of
atherosclerosis and cardiovascular events. Antagonism of IL-1
pathways has been shown to prevent β-cell dysfunction and to
improve glycaemia, cardiovascular complications and heart failure
and it may counteract other complications of diabetes. Therefore,
targeting this pathway in patients with T2D may have numerous
therapeutic advantages over current treatments. (Reviewed by Donath
and Dinarello Nature Reviews 2019).
About Dr. Marc Donath, Principal
Investigator
Prof. Dr. Marc
Donath is the Chief Physician, Clinic of Endocrinology,
Diabetes & Metabolism, University of Basel. Dr. Donath's research aims at the
understanding of the pathogenesis of type 2 diabetes, specifically
to identify the inflammatory process underlying failure of insulin
production in type 2 diabetes. Dr. Donath's work has contributed to
the concept that the innate immune system is an integral component
in the regulation of metabolism and shows that modulation of the
immune system with anti-inflammatory intervention may improve the
overall metabolic health and reduce cardiovascular risk in patients
with type 2 diabetes.
About the INTERCEPT-T2D Consortium
INTERCEPT-T2D,
which stands for Early Interception of Inflammatory-mediated Type 2
diabetes, coordinated by Nicolas Venteclef U1151 at INSERM (French
National Institute of Health and Medical Research) represents a
consortium of entities including Olatec, and several established
European diabetes centers in addition to the Hôpital
Lariboisière, Hôpital Bichat-Claude Bernard and Hôpital
Cochin in Paris, France; German Diabetes Center,
Düsseldorf, Germany; and
University Hospital of Liège in Belgium. Funding is being provided from both
(i) European Union under the Horizon Europe Programme (GA
101095433) and (ii) the Swiss Government as part of the Horizon
Europe Programme and State Secretariat for Education Research and
Innovation, respectively.
About Olatec Therapeutics, Inc.
Olatec is a
leading, clinical-stage biopharmaceutical company developing a
platform of oral NLRP3 inhibitors to treat and prevent a broad
spectrum of acute and chronic inflammatory diseases. The lead drug
candidate, dapansutrile (lab code: OLT1177®) is a small
molecule, specific NLRP3 inhibitor, currently in Phase 2/3 clinical
development has demonstrated to date that it is well tolerated and
shown to improve clinical outcomes in patients with acute gout
flare (see The Lancet Rheumatology) and heart failure
(see Journal of Cardiovascular Pharmacology). In the
heart failure trial, treatment with dapansutrile in subset of
subjects with diabetes led to clinically meaningful reductions in
fasting glucose levels relative to placebo. Ongoing clinical trials
are evaluating dapansutrile in Gout, Parkinson's and Melanoma. For
a complete list of Olatec's original publications on dapansutrile
in various preclinical and clinical disease areas, please refer to
Olatec's publications page, here. For more information, please
visit http://www.olatec.com
Disclaimer & Forward-looking
Statement
This press release is not an offer to sell
and is not soliciting an offer to buy any equity interests in the
Company. The information contained herein is being provided for
information purposes only. The Company makes no express or implied
representation or warranty as to the completeness of this
information. Any forward-looking statements contained in this
release are based on assumptions made by Olatec at the time this
Press Release was prepared. Any forward-looking statement contained
in this Press Release is subject to known and unknown risks,
uncertainties and other factors that may be materially different
from those contemplated in such forward-looking statements. All
information with respect to industry data has been obtained from
sources believed to be reliable and current, but the accuracy
thereof cannot be guaranteed by the Company. Olatec does not
undertake any obligation to update or revise the forward-looking
statements contained in this Press Release to reflect events or
circumstances occurring after the date this Press Release was
prepared, or to reflect the occurrence of unanticipated
events.
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SOURCE Olatec Therapeutics, Inc.