Expert opinion on investigational drugs
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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.
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Expert Opin Investig Drugs · Nov 2014
ReviewExperimental trials in amyotrophic lateral sclerosis: a review of recently completed, ongoing and planned trials using existing and novel drugs.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that affects roughly 2 subjects per 100,000 in the United States; however, given the rapid decline and mortality, there are low prevalence rates. Although ALS is considered a single disease, it, in truth, probably represents a series of disorders with different clinical patterns and different pathophysiologic mechanisms that eventually coalesce into a single entity. The challenge has been to target these different pathophysiologic abnormalities, and so far, most drug studies have focused on only one or two different pathways. Over 50 well-designed clinical trials have been conducted in ALS over the last 25 years and with the exception of the Riluzole trial, all have failed. ⋯ The challenge remains for developing effective targeted therapeutic interventions for ALS. However, with improved recognition of the complex interplay of several factors that may contribute to ALS pathogenesis, in addition to improved patient selection criteria, outcome measures and biomarkers for drug development, advancements may be made in the future.
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Expert Opin Investig Drugs · Oct 2014
Review Comparative StudyZucapsaicin for the treatment of neuropathic pain.
Neuropathic pain (NP) is a chronic disease that stems from a primary lesion or dysfunction of the central or peripheral nervous system. Zucapsaicin is a synthetic cis isomer of natural capsaicin that has shown therapeutic efficacy in pain accompanying osteoarthritis of the knee. It is also currently under investigation for the relief of severe pain in adults suffering from NP. ⋯ The mechanism of action and clinical indications of zucapsaicin are similar to that of its naturally occurring isomer, capsaicin. However, in contrast to capsaicin, zucapsaicin is better tolerated. In the future, zucapsaicin could become a valuable drug for treating pain relief. Indeed, it is possible, in addition to providing NP relief, that it may have a use in treating osteoarthritic pain, headaches and pain that accompany intestinal diseases.
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Expert Opin Investig Drugs · Aug 2014
ReviewSelective JAK inhibitors in development for rheumatoid arthritis.
The JAK kinases are a family of four tyrosine receptor kinases that play a pivotal role in cytokine receptor signalling pathways via their interaction with signal transducers and activators of transcription proteins. Selective inhibitors of JAK kinases are viewed as of considerable potential as disease-modifying anti-inflammatory drugs for the treatment of rheumatoid arthritis. ⋯ JAK inhibitors are effective in the treatment of rheumatoid arthritis as evidenced by several inhibitors enabling the majority of treated patients to achieve ACR20 responses, with baricitinib and INCB-039110 both effective when administered once daily. JAK inhibitors differ in isoform specificity profiles, with good efficacy achievable by selective inhibition of either JAK1 (filgotinib or INCB-039110) or JAK3 (decernotinib). It remains to be seen what selectivity provides the optimal side-effect profile and to what extent inhibition of JAK2 should be avoided.