Expert opinion on investigational drugs
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Expert Opin Investig Drugs · Jan 2015
ReviewFocus on ceftazidime-avibactam for optimizing outcomes in complicated intra-abdominal and urinary tract infections.
Complicated intra-abdominal infections and urinary tract infections are frequently associated with Gram-negative bacteria and treatment can be hampered by the involvement of resistant organisms. A common resistance mechanism is β-lactamase production which confers resistance to β-lactam antibiotics. ⋯ The increasing problem and complexity of β-lactamase resistance has been met by resurgence in the development of β-lactamase inhibitor combinations. These show promise in the treatment of resistant infections. One β-lactamase inhibitor in advanced development with a broad spectrum of activity is avibactam, covering class A, class C and some class D enzymes. Importantly, the activity of avibactam also includes carbapenemases such as the KPC and OXA-48. The combination of avibactam with the cephalosporin ceftazidime is attractive, given the spectrum of antimicrobial activity and the low toxicity of the cephalosporin class.
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Expert Opin Investig Drugs · Jan 2015
ReviewFinerenone : third-generation mineralocorticoid receptor antagonist for the treatment of heart failure and diabetic kidney disease.
The mineralocorticoid receptor antagonists (MRAs) spironolactone and eplerenone reduce the risk of hospitalizations and mortality in patients with heart failure (HF) with reduced ejection fraction (HFrEF), and attenuate progression of diabetic kidney disease. However, their use is limited by the fear of inducing hyperkalemia, especially in patients with renal dysfunction. Finerenone is a novel nonsteroidal MRA, with higher selectivity toward the mineralocorticoid receptor (MR) compared to spironolactone and stronger MR-binding affinity than eplerenone. ⋯ The selectivity and greater binding affinity of finerenone to the MR may reduce the risk of hyperkalemia and renal dysfunction and thereby overcome the reluctance to start and uptitrate MRAs in patients with HF and diabetic kidney disease. Studies conducted in patients with HFrEF and moderate chronic kidney disease and diabetic kidney disease, showed promising results. Phase III trials will have to show whether finerenone might become the third-generation MRA for the treatment of HF and diabetic kidney disease.
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Expert Opin Investig Drugs · Jan 2015
EditorialSuccesses and setbacks of early investigational drugs for melanoma.
Treatment of advanced and metastatic melanoma is a rapidly changing field. Over the past 10 years, there have been six new drugs approved by the FDA for the treatment of metastatic melanoma. These approved drugs include a number of immune checkpoint inhibitors and MAPK-pathway-targeted therapies. ⋯ While these agents have succeeded in both early and later phase clinical trials, a large number of investigational therapies have not yet been developed or researched past Phase I clinical studies. Furthermore, there are dozens of potential agents in Phase I and Phase II clinical development that appear promising and are currently being explored. The field currently aims to determine the optimal sequence and combination of these therapies to best overcome such setbacks as toxicity and resistance and build upon the successes previously seen.