Palatin Technologies, Inc. announced initial data from the BREAKOUT study. The BREAKOUT study is a phase IIb, multicenter, open-label, prospective study of BREmelanotide in diabetic nephropathy to evaluate the effectiveness of reducing urinary protein and maintaining podocyte density and function. The BREAKOUT study (BMT-701) enrolled 16 patients with confirmed type 2 diabetic nephropathy and a UP/Cr ratio >1000 mg/gm, 8 of whom completed six months of treatment, at multiple sites in the United States. United.
Patients received bremelanotide subcutaneously twice daily, in addition to their maximum tolerated dose of renin-angiotensin-aldosterone system (RAAS) inhibitor therapy, and were followed for a control period. The study showed that bremelanotide treatment for six months, in patients with established type II diabetic nephropathy, yielded positive and beneficial results for the majority of patients in terms of worsening kidney function and the progression of the disease. Clinically meaningful endpoints included: >30% reduction in urinary protein to creatinine ratio (UP/Cr) in 71% of patients, improvement or stabilization of estimated glomerular filtration rate (eGFR) in 71% of patients. patients, an increase in urinary levels of vascular endothelial growth factor (VEGF) in 37.5% of patients and a reduction in urinary loss of synaptopodin in 36% of patients.
Bremelanotide was well tolerated. No serious adverse events were attributed to treatment with bremelanotide. The most common adverse reaction was skin hyperpigmentation, occurring in 71% of patients.
Diabetic nephropathy (DN), a severe microvascular complication of diabetes mellitus, is the most common form of chronic kidney disease (CKD) and one of the leading causes of end-stage renal disease. No treatment currently available provides a complete cure. DN is a chronic complication of diabetes and the leading cause of end-stage renal disease, a specific microvascular disease that is the leading cause of death in type 1 diabetes (T1D).
In type 2 diabetes (T2D), DN significantly increases the mortality and disability of diabetic patients, and its degree of malignancy is second only to that of cardiovascular diseases.3 Recent data indicate that approximately 9% of the global adult population is affected by DN, and that the prevalence of DN is nearly 70% among diabetic patients; 592 million people are predicted to have diabetes worldwide by 2035.4?6 An estimated 47.66% of diabetic patients have DN, representing a major challenge in treating the disease. DN is also the leading cause of kidney failure in diabetic patients. The melanocortin receptor (“MCR”) system has effects on inflammation, immune system responses, metabolism, food intake, and sexual function.
There are five melanocortin receptors, MC1R to MC5R. Modulation of these receptors, through the use of receptor-specific agonists, which activate receptor function, or receptor-specific antagonists, which block receptor function, can have medically important pharmacological effects. Many tissues and immune cells in the eye (and other locations, e.g. the gut and kidney) express melanocortin receptors, which directly activate natural pathways to resolve inflammation of the 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 U.S. patients suffer from chronic kidney disease secondary to the combination of hypertension and type II diabetes mellitus. Despite this remarkable prevalence, there is little agreement among clinicians on what constitutes optimal therapy.
Although 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). Therefore, much effort has been devoted to understanding the mechanisms by which the diabetic condition leads to the typical histopathological changes, including mesangial expansion, thickening of basement membranes and loss of density and functionality. podocytes. There is evidence that glomerular podocyte injury is central to the pathogenesis of diabetic nephropathy and clinical treatments should aim to maintain podocyte viability.
Podocytes are highly differentiated, neuron-like cells with limited cell division and replacement capacity. They play a central role in the support and maintenance of glomerular capillary networks and constitute the last barrier in glomerular filtration. Preclinical studies in animal models suggest that podocyte loss precedes and contributes to progressive diabetic glomerulopathy.
Melanocortin receptors constitute a complex system composed of 5 different receptors with broad and varied physiological functions. MC1r signals through a G protein-coupled pathway that results in activation of adenylate cyclase and ultimately stimulation of the serine-threonine kinase activity of protein kinase A A growing body of work on cell signaling and glomerular podocyte function suggests that protein kinase A regulates footplate formation, cell attachment, and apoptosis. Activation of MC1r could stabilize podocyte function and survival in diabetes and other glomerular diseases.
Palatin is a biopharmaceutical company developing first-in-class medicines based on molecules that modulate the activity of melanocortin receptor systems, with targeted, receptor-specific product candidates for the treatment of diseases with high unmet medical needs and the commercial potential is significant. Palatin’s strategy is to develop products and then form commercial collaborations with industry leaders to maximize their commercial potential.
