Emerging small and large molecule therapeutics for respiratory syncytial virus.
Authors: Bergeron HC, Tripp RA Abstract Introduction. Respiratory syncytial virus (RSV) causes lower respiratory tract infections and can lead to morbidity and mortality in the infant, elderly and immunocompromised. There is no vaccine and therapeutic interventions are limited. RSV disease research has yielded the development of several prophylactic and therapeutic treatments. Several promising candidates are currently under investigation.Areas covered. Small and large molecule approaches to RSV treatment were examined and categorized by their mechanism of action using data from PubMed, clinicaltrials.gov, and from...
Source: Expert Opinion on Investigational Drugs - February 26, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Neuropathic pain: preclinical and early clinical progress with voltage-gated sodium channel blockers.
Authors: Kushnarev M, Pirvulescu IP, Candido KD, Knezevic NN Abstract Introduction: Neuropathic pain is a chronic condition that significantly affects the quality of life of millions of people globally. Most of the pharmacologic treatments currently in use demonstrate modest efficacy and over half of all patients do not respond to medical management. Hence, there is a need for new, efficacious drugs. Evidence points toward voltage-gated sodium channels as a key target for novel analgesics.Area covered: The role of voltage-gated sodium channels in pain pathophysiology is illuminated and the preclinical and clinical ...
Source: Expert Opinion on Investigational Drugs - February 21, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

The role of emerging biomarkers in the treatment of non-small cell lung cancer: current challenges and the way forward.
Authors: Malapelle U, Muscarella LA, Pisapia P, Rossi A Abstract Introduction: Driver molecular aberrations, such as EGFR and BRAF mutations, ALK and ROS1 rearrangements, play an important role in the oncogenesis of non-small-cell lung cancer (NSCLC). Overall, these molecular targets select about 20% of advanced nonsquamous NSCLC Caucasian patients who can be treated with the corresponding tyrosine kinase inhibitors (TKIs). Many novel driver mutations are being or have been investigated in NSCLC, with varying degrees of success and failure. These emerging molecular targets are responsible for both primary involveme...
Source: Expert Opinion on Investigational Drugs - February 21, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

The treatment of acute agitation associated with psychosis or mania: investigational drugs in early clinical development, clinical context and potential place in therapy.
Authors: Ward K, Citrome L Abstract INTRODUCTION: Acute agitation in patients with schizophrenia or bipolar disorder may require pharmacologic management before it progresses to aggressive behavior. Ideal medication characteristics for this indication include rapid onset, minimal side effects, and non-invasive administration techniques.Areas Covered: This review summarizes investigational agents in early clinical development for the management of acute agitation in patients with psychosis or mania; it also assesses where these agents may fit with current therapies to provide a clinical perspective. The authors cond...
Source: Expert Opinion on Investigational Drugs - February 9, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

CTLA4-Ig (abatacept): a promising investigational drug for use in type 1 diabetes.
This article examines CTLA4-Ig and its efficacy and safety profiles. Finally, the pharmacokinetic parameters and pharmacodynamic markers of abatacept are shown in-vivo and in clinical trials, guiding dosage regimen recommendations for future investigational studies.Expert opinion:Immunomodulation is one of the promising strategies for decelerating the progression of beta cell destruction after the onset of T1D. It holds the advantage of specific immune modulation without systemic general immunosuppression. Preclinical and clinical studies have yielded promising data on the use of CTLA4-Ig in T1D. Variations in response to ...
Source: Expert Opinion on Investigational Drugs - February 9, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Investigational drugs to treat hemophilia.
Authors: Franchini M, Marano G, Pati I, Veropalumbo E, Vaglio S, Pupella S, Masiello F, Cruciani M, Mengoli C, Liumbruno GM Abstract Introduction: Hemophilia A and B are congenital bleeding disorders. The current standard management of patients with severe hemophilia is prophylaxis which is given intravenously two or three times weekly; however, this is associated with a significant burden on the quality of life of the patient. The main attempts to improve the management of hemophilia is hence through the development of a new generation of products with properties facilitating prophylaxis and/or a better control of...
Source: Expert Opinion on Investigational Drugs - February 6, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Fatty liver disease and primary liver cancer: disease mechanisms, emerging therapies and the role of bariatric surgery.
Authors: Selby LV, Ejaz A, Brethauer SA, Pawlik TM PMID: 31986920 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - January 30, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Benefits and limitations of extended plasma half-life factor VIII products in hemophilia A.
This article reviews the benefits offered by the currently licensed extended half-life products and examines numerous limitations, unmet needs and knowledge gaps.Expert Opinion. FVIII replacement remains the standard of care in patients with hemophilia A, however, there has been advances in novel treatment approaches. Non-factor products such as emicizumab offer a promising alternative that warrants more real-life experience and a direct comparison with FVIII replacement. PMID: 31990229 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - January 30, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Combination therapies currently under investigation in phase I and phase II clinical trials for HIV-1.
This report provides a review of investigational drugs and cell-based interventions against HIV infection that are currently under Phase I or Phase II clinical trials. We report on new antiretroviral drugs, antibodies directed against viral or host targets, reactivating agents, immune modulators and immune checkpoint inhibitors, and cell-based interventions. These new therapies are often tested in combination, including with current antiretroviral drugs. Expert opinion: Islatravir and GS-6207 are promising antiretroviral drugs that are expected to perform well in phase III trials. Whether the host immune system can be acti...
Source: Expert Opinion on Investigational Drugs - January 30, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

NASH and NAFLD: Emerging drugs, therapeutic targets and translational and clinical challenges.
Authors: Alkhouri N PMID: 31984804 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - January 29, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

A randomized phase I pharmacokinetic trial comparing the potential biosimilar adalimumab (CinnoRA ®) with the reference product (Humira®) in healthy volunteers.
Conclusions: The results clearly showed the pharmacokinetic similarity of the biosimilar adalimumab to the originator. CinnoRA® was safe and well-tolerated in healthy volunteers, with no significant differences in safety from the reference product. PMID: 31985294 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - January 29, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Investigational plasma kallikrein inhibitors for the treatment of diabetic macular edema: an expert assessment.
Authors: Bhatwadekar AD, Kansara V, Ciulla T Abstract Introduction: Plasma kallikrein is a mediator of vascular leakage and inflammation. Activation of plasma kallikrein can induce features of diabetic macular edema (DME) in preclinical models. Human vitreous shows elevated plasma kallikrein levels in patients with DME. Because of the incomplete response of some patients to anti-VEGF agents, and the treatment burden associated with frequent dosing, there is still considerable need for VEGF-independent targeted pathways.Areas Covered: This review covers the role of plasma kallikrein in the pathogenesis of DME and th...
Source: Expert Opinion on Investigational Drugs - January 29, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Dr J örn Schattenberg sheds light on key treatment and diagnostic approaches to non-alcoholic steatohepatitis (NASH)Dr Jörn Schattenberg sheds light on key treatment and diagnostic approaches to non-alcoholic steatohepatitis (NASH) By Dr Debbie Tranter, Commissioning Editor.
Dr Jörn Schattenberg sheds light on key treatment and diagnostic approaches to non-alcoholic steatohepatitis (NASH)Dr Jörn Schattenberg sheds light on key treatment and diagnostic approaches to non-alcoholic steatohepatitis (NASH) By Dr Debbie Tranter, Commissioning Editor. Expert Opin Investig Drugs. 2020 Jan 27;: Authors: Schattenberg JM PMID: 31985310 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - January 29, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH): Prevalence, therapeutic innovations and stumbling blocks for clinical development.
Authors: Alkhouri N PMID: 31971024 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - January 24, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Targeting CCR2/5 in the treatment of non-alcoholic steatohepatitis (NASH) and fibrosis: opportunities and challenges.
Authors: Lefere S, Devisscher L, Tacke F PMID: 31952447 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - January 20, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Fibroblast growth factor (FGF)-21 based therapies: A magic bullet for nonalcoholic fatty liver disease (NAFLD)?
This article summarizes preclinical and clinical data on the efficacy and safety of two FGF21 agonist therapies in developmentExpert Opinion: Preclinical and clinical data justify further investigation of FGF21 agonist therapies for the treatment of NAFLD. However, issues including injection site reactions and possible effects on bone homeostasis means that safety must be evaluated carefully. PMID: 31948295 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - January 19, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Targeting the Wnt signalling pathway: the challenge of reducing scarring without affecting repair.
This article seeks to shed light on the dualistic role of Wnt signalling in liver regeneration following injury and how Wnt signalling can regulate scar formation. It also discusses how Wnt signalling cooperates with other classical fibrogenic signalling cascades, such as TGFβ signalling. Finally, the article examines recent advances in the development of Wnt signalling pathway inhibitors and asks whether repurposing these agents as anti-fibrotic therapies is a realistic option.Expert Opinion: The understanding of Wnt signalling in liver regeneration and fibrosis is in its infancy and whilst new generations of Wnt pat...
Source: Expert Opinion on Investigational Drugs - January 19, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Use of a bioengineered antioxidant in mouse models of metabolic syndrome.
Conclusions: PEG-HCC can improve some parameters of disease in these models and this may be due to a resulting increase in peripheral insulin sensitivity. However, additional studies are needed to elucidate how PEG-HCCs are producing these effects. PMID: 31937152 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - January 17, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Effectiveness of lifestyle interventions in NALFD (non-alcoholic fatty liver disease) - how are clinical trials affected?
Authors: Michel M, Schattenberg JM PMID: 31933385 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - January 16, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

NASH (non-alcoholic steatohepatitis), diabetes, and macrovascular disease: multiple chronic conditions and a potential treatment at the metabolic root.
Authors: Colca J Abstract Introduction: NASH and type 2 diabetes (T2D) are clinical definitions that overlap and result from metabolic dysfunction caused by over-nutrition relative to metabolic need. This volume details drug development programs aimed at specific NASH pathology with a focus on liver outcomes; this commentary suggests a metabolic approach that should not be overlooked based on a new understanding of insulin sensitizers.Areas covered: The overlap of NASH and T2D with respect to metabolic syndrome are discussed in the context of new understandings of insulin sensitizers. Adverse clinical outcomes in s...
Source: Expert Opinion on Investigational Drugs - January 14, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Phase I/II parallel double-blind randomized controlled clinical trial of perispinal etanercept for chronic stroke: improved mobility and pain alleviation.
Authors: Ralph SJ, Weissenberger A, Bonev V, King LD, Bonham MD, Ferguson S, Smith AD, Goodman-Jones AA, Espinet AJ Abstract Background: Previous open-label studies showed that chronic post-stroke pain could be abated by treatment with perispinal etanercept, although these benefits were questioned. A randomized double-blind placebo controlled clinical trial was conducted to test perispinal etanercept for chronic post-stroke pain.Research design and methods: Participants received two treatments, either perispinal etanercept (active) or saline (control). Primary outcomes were the differences in daily pain levels betw...
Source: Expert Opinion on Investigational Drugs - January 6, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Pegbelfermin (BMS-986036): an investigational PEGylated fibroblast growth factor 21 analogue for the treatment of nonalcoholic steatohepatitis.
Authors: Verzijl CRC, Van De Peppel IP, Struik D, Jonker JW Abstract Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and is strongly associated with obesity and insulin resistance. NAFLD refers to a spectrum of disorders ranging from asymptomatic hepatic steatosis (nonalcoholic fatty liver, NAFL) to nonalcoholic steatohepatitis (NASH), which increases the risk of developing more severe forms of liver disease such as progressive fibrosis, cirrhosis, and liver cancer. Currently, there are no food and drug administration (FDA) approved drugs to treat NASH. Pegbelfermin...
Source: Expert Opinion on Investigational Drugs - January 6, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Thyromimetics as emerging therapeutic agents for nonalcoholic steatohepatitis: rationale for the development of Resmetirom (MGL-3196).
Authors: Alkhouri N PMID: 31868036 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - December 24, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Cyclophilin inhibition as a potential treatment for nonalcoholic steatohepatitis (NASH).
This articles briefly describes cyclophilin isomerases and the main classes of cyclophilin antagonists; it then summarizes data showing cyclophilin participation in the major pathophysiological activities that occur in NASH.Expert Opinion: Optimization of therapeutic outcomes in the treatment of NASH may be best realized by targeting multiple pathologic pathways, especially when treating advanced stages of the disease. A preferred approach for achieving this goal is to use compounds such as cyclophilin inhibitors that simultaneously target multiple disease processes. The pleiotropic benefits of this drug class derive from ...
Source: Expert Opinion on Investigational Drugs - December 24, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Investigational Drugs in Phase II Clinical Trials for Acute Coronary Syndromes.
Authors: Rout A, Sukhi A, Chaudhary R, Bliden KP, Tantry US, Gurbel PA Abstract Introduction: Despite current guideline-based, secondary prevention strategies in patients with the acute coronary syndrome, the residual ischemic risk is still at an unacceptable rate, and there is a concomitant high bleeding event rate. These observations mandate investigations of novel treatment strategies to meet the unmet need to improve outcomes in patients with ACS.Areas covered: In this review, the author(s) focus on new agents with ongoing or recently completed phase II trials for the treatment of ACS. We searched MEDLINE and c...
Source: Expert Opinion on Investigational Drugs - December 24, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Emerging drugs in randomized controlled trials for sickle cell disease: are we on the brink of a new era in research and treatment?
This article offers an overview of the key studies of new therapeutic options for SCD. We searched the PubMed database and Cochrane Database of Systemic Reviews for agents in early phase clinic trials and preclinical development.Expert Opinion: Although knowledge of SCD has progressed, patient survival and quality of life must be improved. Phase II and III clinical trials investigating pathophysiology-based novel agents show promising results in the clinical management of SCD acute events. The design of long-term clinical studies is necessary to fully understand the clinical impact of these new therapeutics on the natural ...
Source: Expert Opinion on Investigational Drugs - December 20, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Selinexor (KTP-330) - a selective inhibitor of nuclear export (SINE): anti-tumor activity in diffuse large B-cell lymphoma (DLBCL).
This article reviews the available data from clinical trials regarding the efficacy of selinexor in DLBCL and highlights the key toxicity issues and how they may best be managed. Ongoing and future studies in DLBCL are also discussed.Expert opinion: More translational studies are necessary to leverage the unique mechanism action and rationally inform the use of selinexor in combination strategies. There are several different genetic subtypes of DLBCL, but it is not clear if these classifications will identify patients that may benefit from targeted therapies. The broad potential mechanism of action of selinexor will requir...
Source: Expert Opinion on Investigational Drugs - December 20, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Obesity medications in development.
Authors: Rebello CJ, Greenway FL Abstract Introduction: Obesity is compounded by a neurobiology that is resistant to weight loss. Therefore, the development of pharmacotherapies to address the pathology underlying the dysregulation of energy homeostasis is critical.Areas covered: This review examines selected clinical trial evidence for the pharmacologic treatment of obesity and provides an expert opinion on anti-obesity drug development. The article includes the outcomes of anti-obesity medications that have been evaluated in clinical trials but have not yet received approval from the U.S. Food and Drug Administra...
Source: Expert Opinion on Investigational Drugs - December 20, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

The molecular basis for current targets of NASH therapies.
Authors: Qureshi K, Neuschwander-Tetri BA Abstract Introduction Nonalcoholic steatohepatitis (NASH) is a leading cause of liver disease in children and adults, a major contributor to healthcare expenditures, and now a leading reason for liver transplantation. Adopting lifestyle modifications with regular exercise and a focus on health eating habits is the primary recommendation. However, patients are often unable to achieve and sustain such changes for a variety of social, physical, psychological and genetic reasons. Thus, treatments that can prevent and reverse NASH and its associated fibrosis are a major focus of...
Source: Expert Opinion on Investigational Drugs - December 20, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Trends in pioglitazone use among US adults with type 2 diabetes and suspected non-alcoholic fatty liver disease.
Authors: Le P, Chaitoff A, Rothberg MB, McCullough A, Alkhouri N Abstract BackgroundWe aimed to estimate population-based trends in prevalence of coexisting type 2 diabetes (T2D) and suspected non-alcoholic fatty liver disease (NAFLD) and pioglitazone use among US adults.Research design and methodsWe conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey from 2003-2016. We included people aged ≥18 years who had HbA1C>6.4%, fasting plasma glucose>125 mg/dL, or were told they had diabetes by a doctor. Suspected NAFLD was defined using hepatic steatosis index of>36. Pr...
Source: Expert Opinion on Investigational Drugs - December 14, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

P2-Purinoceptors: Advances and therapeutic opportunities.
Authors: Williams M, Jacobson KA Abstract The recent cloning of a number of distinct receptors belonging to the P2-purinoceptor superfamily has provided conclusive evidence for a pivotal role for ATP and other nucleotides as effector molecules involved in cell-to-cell communication and the modulation of many basic aspects of tissue function. ATP itself is being clinically evaluated as a cytotoxic agent for the treatment of cancer and as an adjunct to inhalation anaesthetic use. The pyrimidine nucleotide, UTP, is in clinical trials for the treatment of cystic fibrosis. The stable ATP bioisostere, ARL 67085, is being...
Source: Expert Opinion on Investigational Drugs - December 14, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Etripamil nasal spray: an investigational agent for the rapid termination of paroxysmal supraventricular tachycardia (SVT).
Authors: Kashou AH, Noseworthy PA Abstract Introduction: Paroxysmal supraventricular tachycardia (SVT) can be very bothersome and may potentially lead to considerable health-care utilization. Non-parenteral medication is currently unavailable for the rapid termination of paroxysmal SVT. However, an intranasal spray formulation of etripamil, a short-acting calcium-channel blocker, is under investigation as a convenient, safe, and rapidly efficacious means to terminate paroxysmal SVT.Areas covered: This review summarizes the clinical rationale, potential benefit, and clinical trials safety and efficacy data for the u...
Source: Expert Opinion on Investigational Drugs - December 13, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Filanesib for the treatment of multiple myeloma.
This article provides a comprehensive overview about the progress to date in the preclinical and clinical development of filanesib for the treatment of cancer, and particularly, MM.Expert opinion: Responses observed with filanesib alone or in combination with dexamethasone were encouraging in MM. However, the subsequent appearance of highly effective novel agents such as monoclonal antibodies, has hindered the development of agents such as filanesib that exhibit a more limited activity. Nevertheless, filanesib has shown interesting results for some patients when combined with carfilzomib and pomalidomide. Most importantly,...
Source: Expert Opinion on Investigational Drugs - December 11, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Investigational CHK1 inhibitors in early phase clinical trials for the treatment of cancer.
Authors: Dent P Abstract Introduction: Checkpoint kinase 1 (CHK1) inhibitors have been in development for two decades. The initial CHK1 inhibitor staurosporine analog, UCN01, entered clinical trials whilst it was still considered to act via PKC inhibition; only later were trials performed in a more focused fashion to determine whether CHK1 inhibition could dysregulate cell cycle checkpoints. Many of the subsequently synthesized more specific CHK1 inhibitors have failed because of poor PK/PD or cumulative normal tissue toxicities in patients. CHK1 inhibitor monotherapy often demonstrates limited efficacy and in gene...
Source: Expert Opinion on Investigational Drugs - December 1, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

MET inhibitors in cancer: Pitfalls and challenges.
This article provides a systematic review of phase II randomized and phase III clinical trials investigating the use of MET inhibitors in the treatment of cancer. We discuss preliminary findings on efficacy and methodologic design flaws in these trials.Expert opinion: MET inhibitors showed poor activity in unselected patients or patients selected by MET expression, p-MET or high HGF basal levels. The efficacy in advanced solid tumors is very modest and in phase III clinical trials, survival differences did not fulfill the stringent requirements of ESMO-Magnitude Clinical Benefit Score (MCBS). Prospective novel liquid bioma...
Source: Expert Opinion on Investigational Drugs - December 1, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Personalized pharmacological therapy for ARDS: a light at the end of the tunnel.
Authors: Silva PL, Pelosi P, Rocco PRM Abstract Introduction: Pharmacotherapy for the acute respiratory distress syndrome (ARDS) has been tested in preclinical and clinical studies. However, to date, no pharmacological interventions have proven effective. This may be attributed to lack of proper identification of different ARDS phenotypes.Areas covered: We designed inclusive search strings and searched four bibliographic databases (Cochrane Database of Systematic Reviews, PubMed, Web of Science, and clinicaltrials.gov) to identify relevant research. Search results were mainly restricted to papers published from 200...
Source: Expert Opinion on Investigational Drugs - November 30, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Investigational drugs in development for hypertriglyceridemia: a coming-of-age story.
Authors: Rhainds D, Brodeur MR, Tardif JC Abstract Introduction - Elevated triglyceride (TG) level is a prevalent condition in the general population and in patients with cardiovascular (CV) risk even under statin therapy. Severe hypertriglyceridemia (HTG) puts patients at risk for acute pancreatitis. Several TG-lowering drugs failed in clinical trials, but subgroup analyses suggest that high-risk patients, such as those with atherogenic dyslipidemia or diabetes, benefit from TG lowering.Areas covered - We review advances for TG-lowering drugs in clinical development. These include selective PPARs modulators, omega...
Source: Expert Opinion on Investigational Drugs - November 24, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Tyrosine kinase inhibitors for the treatment of rheumatoid arthritis: phase I to Ⅱ clinical trials.
We examined the literature published between January 2014 to January 2019 using electronic databases including PubMed, Web of Science, Medline, Embase and Google Scholar. Additional information about phase I and II trials on the ClinicalTrial.gov website up to January 2019 was also retrieved.Expert opinion: JAK inhibitors are promising drugs with sound efficacy and acceptable safety and may be beneficial to patients who do not respond to DMARDs and biologicals. The response rates among RA patients to TKIs are diverse; genetic and environmental factors may be involved in the varying responses which are closely related to th...
Source: Expert Opinion on Investigational Drugs - November 20, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Insights into HIV-1 capsid inhibitors in preclinical and early clinical development as antiretroviral agents.
Authors: Cevik M, Orkin C PMID: 31738620 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - November 20, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Mucinous ovarian cancer: current therapeutic targets, preclinical progress and experimental drugs.
Authors: Moioli M, Barra F, Maramai M, Valenzano Menada M, Vellone VG, Costantini S, Ferrero S PMID: 31726889 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - November 18, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

DNX-2401: an investigational drug for the treatment of recurrent glioblastoma.
Authors: Philbrick B, Adamson DC Abstract INTRODUCTION: High grade gliomas (HGG) are extremely aggressive brain malignancies that are usually fatal. Despite maximal resection, chemotherapy and radiation, these tumors inevitably recur and present a poor median overall survival (mOS); hence there is a pressing need for improved treatments.Areas covered:This review assesses DNX-2401 as a treatment of recurrent HGG. Phase I data on efficacy, safety, and tolerability are examined while insights and perspectives on future directions are offered.Expert opinion:This phase I study assessed DNX-2401 in two groups; one group ...
Source: Expert Opinion on Investigational Drugs - November 18, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Investigational IGF1R inhibitors in early stage clinical trials for cancer therapy.
Authors: Werner H, Sarfstein R, Bruchim I Abstract Introduction: The insulin-like growth factors (IGF) are a family of secreted peptide hormones with important roles in different cellular and organism functions. The biological activities of the IGFs are mediated by the IGF1 receptor (IGF1R), a cell-surface, tyrosine kinase-containing heterotetramer that is linked to numerous cytoplasmic signaling cascades. The IGF1R displays potent anti-apoptotic, pro-survival capacities and plays a key role in malignant transformation. Research has identified the IGF1R as a candidate therapeutic target in cancer.Areas covered: We ...
Source: Expert Opinion on Investigational Drugs - November 18, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Investigational drugs for the treatment of binge eating disorder (BED): an update.
Authors: Appolinario JC, Nardi AE, McElroy SL Abstract Introduction: Binge eating disorder (BED) is the most common eating disorder and is frequently associated with psychiatric and medical comorbidities and functional impairment. Although psychological treatments have been the cornerstones of BED treatment, pharmacologic interventions also play an important part of the multimodal management of this condition.Areas covered: This review examines investigational, approved and other pharmacological agents for the treatment of BED. We searched PubMed and clinicaltrials.gov to identify pharmacological interventions for ...
Source: Expert Opinion on Investigational Drugs - November 14, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Investigational BACE inhibitors for the treatment of Alzheimer's disease.
Authors: Imbimbo BP, Watling M Abstract Introduction: The amyloid hypothesis of Alzheimer's disease (AD) states that brain accumulation of amyloid-β (Aβ) oligomers and soluble aggregates represents the major causal event of the disease. Several small organic molecules have been synthesized and developed to inhibit the enzyme (β-site amyloid precursor protein cleaving enzyme-1 or BACE1) whose action represents the rate-limiting step in Aβ production.Areas covered: We reviewed the pharmacology and clinical trials of major BACE1 inhibitors.Expert opinion: In transgenic mouse models of AD, BACE1 inh...
Source: Expert Opinion on Investigational Drugs - October 31, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

BIIB093 (IV Glibenclamide): an investigational compound for the prevention and treatment of severe cerebral edema.
Authors: Pergakis M, Badjatia N, Chaturvedi S, Cronin CA, Kimberly WT, Sheth KN, Simard JM Abstract Introduction: Brain swelling due to edema formation is a major cause of neurological deterioration and death in patients with large hemispheric infarction (LHI) and severe traumatic brain injury (TBI), especially contusion-TBI. Preclinical studies have shown that SUR1-TRPM4 channels play a critical role in edema formation and brain swelling in LHI and TBI. Glibenclamide, a sulfonylurea drug and potent inhibitor of SUR1-TRPM4, was reformulated for intravenous injection, known as BIIB093. Areas covered: We discuss the ...
Source: Expert Opinion on Investigational Drugs - October 20, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

A role for IL-1 inhibitors in the treatment of non-alcoholic steatohepatitis (NAFLD)?
Authors: Tilg H, Effenberger M, Adolph TE PMID: 31615278 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - October 18, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Cyclin-dependent kinase (CDK) 9 and 4/6 inhibitors in acute myeloid leukemia (AML): a promising therapeutic approach.
We describe the rationale for targeting CDK9 and CDK4/6, the ongoing preclinical and clinical trials and the potential of these inhibitors in AML. Our analysis included an extensive literature search via the Pubmed database and clinicaltrials.gov (March to August, 2019). Expert opinion: While CDK4/6 inhibitors are early in development for AML, CDK9 inhibition with alvocidib has encouraging clinical activity in newly diagnosed and relapsed/refractory AML. Preclinical data suggests that leukemic MCL-1 dependence may predict response to alvocidib. Moreover, MCL-1 plays a key role in resistance to BCL-2 inhibition with venetoc...
Source: Expert Opinion on Investigational Drugs - October 17, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Clinical drug development for dementia with Lewy bodies: past and present.
Authors: Lee G, Cummings J, Decourt B, Leverenz JB, Sabbagh MN Abstract Introduction: Dementia with Lewy bodies (DLB) is an under-researched area despite being the second most common type of degenerative dementia after Alzheimer's disease. It is an area of unmet need with no approved symptomatic or disease-modifying therapies. The pharmacological management of DLB is complex and challenging because early trials of drugs for DLB have resulted in no demonstrable efficacy. Randomized controlled trials (RCTs) in the DLB population have only recently been initiated. Understanding results from previous and current clinic...
Source: Expert Opinion on Investigational Drugs - October 17, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Novel investigational therapeutics for generalized anxiety disorder (GAD).
Authors: Schanzer B, Rivas-Grajales AM, Khan A, Mathew SJ Abstract Introduction: Generalized anxiety disorder (GAD) is a common and disabling psychiatric condition that affects 3% of the population and exacts significant costs to society if untreated. There are numerous treatment options available, but all have side effects, and none are reliably effective, hence there is a significant need for new medications. Areas Covered: The authors reviewed clinical Phase II and III studies listed on the clinicaltrials.gov and clinicaltrialsregister.eu websites, 2007-present. Additional information was gathered from the study...
Source: Expert Opinion on Investigational Drugs - October 15, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Siponimod in the treatment of multiple sclerosis.
Authors: Goodman A, Anadani N, Gerwitz L Abstract Introduction: Multiple sclerosis (MS) causes focal lesions of immune-mediated demyelinating events followed by slow progressive accumulation of disability. Over the past 2 decades, multiple medications have been studied and approved for use in MS. Most of these agents work by modulating or suppressing the peripheral immune system. Siponimod is a newer-generation sphingosine 1 phosphate (S1P) receptor modulator which internalizes S1P1 receptors thereby inhibiting efflux of lymphocytes from lymph nodes and thymus. There are promising data suggesting that it may also h...
Source: Expert Opinion on Investigational Drugs - October 12, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research