Palatin Technologies announced positive topline data from its Phase IIb BREAKOUT study, evaluating bremelanotide in patients with confirmed Type 2 diabetic nephropathy. The study demonstrated clinically meaningful improvements in kidney function and disease progression, suggesting a potential new therapeutic strategy for this severe complication of diabetes.
The BREAKOUT study enrolled 16 patients with Type 2 diabetic nephropathy and a urine protein to creatinine ratio (UP/Cr) >1000 mg/gm. Eight patients completed the six-month treatment regimen, receiving twice-daily subcutaneous injections of bremelanotide in addition to their maximum tolerated dose of renin-angiotensin-aldosterone system (RAAS) inhibition therapy.
Key Findings from the BREAKOUT Study
After six months of treatment, 71% of patients achieved a >30% reduction in the urine protein to creatinine ratio (UP/Cr), indicating a significant decrease in proteinuria. Additionally, 71% of patients experienced either improved or stabilized estimated glomerular filtration rate (eGFR), a key measure of kidney function. The therapy also increased urinary vascular endothelial growth factor (VEGF) levels in 37.5% of participants and reduced urinary synaptopodin losses in 36%.
"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.
Bremelanotide and the Melanocortin System
Bremelanotide is a melanocortin receptor agonist that targets all five melanocortin receptors except for the melanocortin 2 receptor. The melanocortin system is involved in regulating inflammation, immune response, metabolism, and other physiological functions. Palatin's approach focuses on harnessing this system to develop targeted therapies for various diseases.
James A. Tumlin MD, CEO and Founder of NephroNet Clinical Trials Consortium, noted, "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. 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."
Safety and Tolerability
Bremelanotide was generally well-tolerated in the study. The most common adverse event was skin hyperpigmentation, which occurred in 71% of patients. No serious adverse events were attributed to bremelanotide treatment.
Implications for Diabetic Nephropathy Treatment
Diabetic nephropathy (DN) is the most common cause of end-stage renal disease in the United States and other developed countries. It affects approximately 9% of the world's adult population and nearly 70% of patients with diabetes. Current treatments are limited, with no available cure, underscoring the urgent need for new therapeutic options.
The positive results from the BREAKOUT study suggest that bremelanotide could offer a novel approach to treating diabetic nephropathy by modulating the melanocortin system to reduce inflammation and promote tissue repair. Palatin is also investigating bremelanotide and other melanocortin-targeted drug candidates for ophthalmic and metabolic conditions, with Phase 2 data from an ongoing trial in ulcerative colitis expected in the first quarter of 2025.
