- Open label study designed to evaluate the safety,
tolerability, and efficacy of bremelanotide in patients with Type 2
diabetic nephropathy
- Demonstrated efficacy at 6 months
- 71% percent of patients achieved a >30% reduction in the
urine protein to creatinine ratio (UP/Cr)
- 71% of patients achieved improved or stabilized
estimated glomerular filtration rate (eGFR)
- Bremelanotide therapy increased urinary VEGF levels in 37.5%
of patients and reduced urinary synaptopodin losses in 36%
of patients
CRANBURY, N.J., Dec. 19,
2024 /PRNewswire/ -- Palatin Technologies, Inc. (NYSE
American: PTN), a biopharmaceutical company developing
first-in-class medicines based on molecules that modulate
the activity of the melanocortin receptor system, today
announced topline data for the BREAKOUT study. The BREAKOUT study
is a Phase IIb, Multicenter, Open-Label, Prospective Study of
BREmelanotide in DiAbetic
Kidney Disease to Assess the Efficacy in Reducing
Urinary PrOtein and Maintaining Podocyte Density and
FUncTion.
The BREAKOUT Study (BMT-701) enrolled 16 patients with confirmed
Type 2 diabetic nephropathy and >1000 mg/gm UP/Cr ratio, with 8
patients completing the six-month treatment regimen, at multiple
sites in the United States.
Patients were administered bremelanotide subcutaneously twice
daily, in addition to their maximum tolerated dose of
renin-angiotensin-aldosterone system (RAAS) inhibition therapy and
monitored through a follow-up period.
The study showed that bremelanotide therapy for six months, in
patients with established Type II diabetic nephropathy, resulted in
positive and beneficial results for the majority of patients
related to worsening kidney function and disease progression.
Clinically meaningful endpoints included; 71% of patients achieved
a >30% reduction in the urine protein to creatinine ratio
(UP/Cr), 71% of patients achieved improved or stabilized estimated
glomerular filtration rate (eGFR), increased urinary vascular
endothelial growth factor (VEGF) levels in 37.5% of patients and
reduced urinary synaptopodin losses in 36% of patients.
"The data from this trial is encouraging and validates that
modulating the melanocortin system could potentially be a new
therapeutic strategy and possibly disease-modifying treatment
option for people living with this progressive kidney disease,"
said Carl Spana, Ph.D., President
and CEO of Palatin. "Targeting the melanocortin system in
autoimmune and inflammation conditions reduces cellular stress,
resolves inflammation and promotes tissue repair. Our melanocortin
pipeline has demonstrated preclinical efficacy in over 10 disease
models, including positive clinical results in this Phase IIb
Diabetic Nephropathy study and our MELODY-1 Phase 3 dry eye
disease trial earlier this year. Lastly, patient enrollment in our
Phase 2 ulcerative colitis trial is complete, with topline data
targeted for release in the first quarter of calendar year
2025."
"The findings from this study are consistent with previous
studies that the activation of melanocortin receptors can result in
positive effects on kidney function by positively effecting
synaptopodin and podocyte function," said James A. Tumlin MD, CEO and Founder of NephroNet
Clinical Trials Consortium. "With diabetic nephropathy being one of
the leading causes of end-stage renal disease across the world,
this positive data supports the further development of a
melanocortin agonist like bremelanotide, without melanocortin-2
receptor agonism, as a potential treatment option for diabetic
nephropathy patients."
Bremelanotide was well tolerated. There were no serious adverse
events attributable to bremelanotide treatment. The most common
adverse event was skin hyperpigmentation, which occurred in 71% of
patients. Additional trial information, including inclusion and
exclusion criteria, can be found at https://clinicaltrials.gov via
the identifier NCT05709444.
Diabetic nephropathy (DN), a severe microvascular complication
of diabetes mellitus (DM), is the most common form of chronic
kidney disease (CKD) and a leading cause of renal failure in
end-stage renal disease. No currently available treatment can
achieve complete cure.
DN is a chronic complication of diabetes and the leading cause
of end-stage kidney disease, a specific microvascular disease that
is the main cause of death in Type 1 DM (T1DM).1,2 In
Type 2 DM (T2DM), DN greatly increases mortality and disability in
patients with diabetes, and its degree of malignancy is second only
to that of cardiovascular disease.3 Recent data has
indicated that approximately 9% of the world's adult population is
affected by DN, and the prevalence of DN is nearly 70% in patients
with diabetes; 592 million people have been predicted to have
diabetes worldwide by the year 2035.4–6 As many as
47.66% of patients with diabetes have been estimated to have DN,
thus posing a major challenge in treating DM. DN is also the
primary cause of kidney failure in patients with
diabetes.7
About Melanocortin Receptor Agonists
The
melanocortin receptor ("MCR") system has effects
on inflammation, immune system responses, metabolism, food intake,
and sexual function. There are five melanocortin
receptors, MC1R through MC5R. Modulation of these receptors,
through use of receptor-specific agonists, which
activate receptor function, or receptor-specific antagonists, which
block receptor function, can have medically significant
pharmacological effects.
Many tissues and immune cells located in the eye (and other
places, for example the gut and kidney) express melanocortin
receptors, empowering our opportunity to directly activate natural
pathways to resolve disease inflammation.
About Diabetic (Nephropathy) Kidney Disease
Diabetic
nephropathy (DN) is the most common cause of end-stage renal
disease in the United States and
other developed countries. Approximately 30 million US patients
have chronic kidney disease (CKD) secondary to the combination of
hypertension and Type II diabetes mellitus. Despite this remarkable
prevalence, clinicians have little consensus on what comprises
optimal therapy. While the widespread use of RAAS blockade and
other maneuvers have slowed disease progression, approximately
one-third of patients with Type II diabetic nephropathy will
progress to end-stage renal disease (ESRD). As a result, much
effort has been devoted to understanding the mechanisms by which
the diabetic condition leads to the typical histopathologic
changes, including mesangial expansion, thickened basement
membranes, and loss of podocyte density and functionality.
There is evidence that injury to the glomerular podocyte is
central to the pathogenesis of diabetic nephropathy and that
clinical treatments should be directed toward maintaining podocyte
viability. Podocytes are highly differentiated neuron-like cells
with limited cell division and replacement capacity. They are
central to the support and maintenance of glomerular capillary
networks and function as the final barrier in glomerular
filtration. Evidence from pre-clinical animal model studies
suggests that podocyte losses precede and contribute to progressive
diabetic glomerulopathy.
About Melanocortins and Kidney Disease
Melanocortin
receptors comprise a complex system comprised of 5 different
receptors with broad and varying physiologic functions. MC1r
signals through a G-protein coupled pathway that leads to
activation of adenylate cyclase and ultimately stimulation of the
serine-threonine kinase activity of protein kinase A. A growing
body of work in cell signaling and function of the glomerular
podocyte suggests that protein kinase A regulates the formation of
footplate processes, cell attachment, and apoptosis. MC1r
activation may stabilize podocyte function and survival in diabetes
and other conditions of glomerular diseases.
About Palatin
Palatin is a biopharmaceutical company
developing first-in-class medicines based on molecules that
modulate the activity of the melanocortin receptor systems, with
targeted, receptor-specific product candidates for the treatment of
diseases with significant unmet medical need and commercial
potential. Palatin's strategy is to develop products and then form
marketing collaborations with industry leaders to maximize their
commercial potential. For additional information regarding Palatin,
please visit Palatin's website at www.Palatin.com and follow
Palatin on Twitter at @PalatinTech.
Forward-looking Statements
Statements in this press
release that are not historical facts, including statements about
future expectations of Palatin Technologies, Inc., such as
statements about Palatin products in development, clinical trial
results, potential actions by regulatory agencies including the
FDA, regulatory plans, development programs, proposed indications
for product candidates, and market potential for product candidates
are "forward-looking statements" within the meaning
of Section 27A of the Securities Act of 1933,
Section 21E of the Securities Exchange Act of 1934 and as that term
is defined in the Private
Securities Litigation Reform Act of 1995. Palatin
intends that such forward-looking statements be subject to the safe
harbors created thereby. Such forward-looking statements involve
known and unknown risks, uncertainties and other factors that could
cause Palatin's actual results to be materially different from its
historical results or from any results expressed or implied by such
forward-looking statements. Palatin's actual results may differ
materially from those discussed in the forward-looking statements
for reasons including, but not limited to,
results of clinical trials, regulatory actions by
the FDA and other regulatory and the need for regulatory approvals,
Palatin's ability to fund development of its technology and
establish and successfully complete clinical trials, the length of
time and cost required to complete clinical trials and submit
applications for regulatory approvals, products developed by
competing pharmaceutical, biopharmaceutical and biotechnology
companies, commercial acceptance of Palatin's products, and other
factors
discussed in Palatin's periodic filings with the Securities and Exchange Commission. Palatin
is not responsible for updating events that occur after the
date of this press release.
Palatin Technologies® is a registered trademark of
Palatin Technologies, Inc.
References
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aggravates diabetic nephropathy by regulating the miR-325/CCNG1
axis. J Healthc Eng. 2022;2022:2279072.
doi:10.1155/2022/2279072
2. Manazir S, Durrani HM, Jawed F, et al. Concurrent
presentation of diabetic nephropathy and type 1 diabetes mellitus
in a pediatric patient. Cureus. 2021;13(12):e20831.
doi:10.7759/cureus.20831
3. Allen A, Iqbal Z, Green-Saxena A, et al. Prediction
of diabetic kidney disease with machine learning algorithms, upon
the initial diagnosis of type 2 diabetes mellitus. BMJ Open
Diabetes Res Care. 2022;10(1):e002560.
doi:10.1136/bmjdrc-2021-002560
4. Wang G, Li Q, Chen D, et al. Kidney-targeted
rhein-loaded liponanoparticles for diabetic nephropathy therapy via
size control and enhancement of renal cellular
uptake. Theranostics. 2019;9(21):6191–6208.
doi:10.7150/thno.37538
5. Nossier AI, Shehata NI, Morsy SM, et al.
Determination of certain urinary microRNAs as promising biomarkers
in diabetic nephropathy patients using gold
nanoparticles. Anal Biochem. 2020;609:113967.
doi:10.1016/j.ab.2020.113967
6. Xiong W, Xiong SH, Chen QL, et al.
Brij-functionalized chitosan nanocarrier system enhances the
intestinal permeability of P-glycoprotein substrate-like drugs.
Carbohydr Polym. 2021;266:118112.
doi:10.1016/j.carbpol.2021.118112
7. Lin S, Yang J, Wu G, et al. Preventive effect of
taurine on experimental type II diabetic nephropathy. J Biomed
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