Ipilimumab: an investigational immunotherapy for glioblastoma.
Authors: Youssef G, Dietrich J Abstract INTRODUCTION: Glioblastoma (GBM) is the most common primary malignant central nervous system tumor and has a poor overall outcome despite an aggressive standard-of-care treatment. Hence, better therapeutic modalities are necessary. Immunotherapy is a novel modality that has an indirect action against the tumor cells through activation of an anti-tumor immune response. AREAS COVERED: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) belongs to a class of molecules called immune checkpoints that are inherently expressed on immune cells and lead to attenuation of the immu...
Source: Expert Opinion on Investigational Drugs - September 20, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Investigational drugs in early phase clinical trials targeting thermotransient receptor potential (thermoTRP) channels.
Authors: Fernández-Carvajal A, González-Muñiz R, Fernández-Ballester G, Ferrer-Montiel A Abstract INTRODUCTION: . Thermo transient receptor potential (thermoTRP) channels are some of the most intensely pursued therapeutic targets of the past decade. They are considered promising targets of numerous diseases including chronic pain and cancer. Modulators of these proteins, in particular TRPV1-4, TRPM8 and TRPA1, have reached clinical development, but none have been approved for clinical practice yet. AREAS COVERED: . The therapeutic potential of targeting thermoTRP channels is discusse...
Source: Expert Opinion on Investigational Drugs - September 19, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Melflufen for relapsed and refractory multiple myeloma.
Authors: Oriol A, Larocca A, Leleu X, Hajek R, Hassoun H, Rodríguez-Otero P, Paner A, Schjesvold FH, Gullbo J, Richardson PG Abstract INTRODUCTION: The overall survival of patients with multiple myeloma has improved with the advent of novel agents; however, multiple myeloma remains incurable. Combinations of standard-of-care agents such as immunomodulators, proteasome inhibitors, and anti-CD38 monoclonal antibodies are increasingly used in earlier lines of therapy. Patients with disease that is refractory to multiple novel agents represent a population with high unmet medical need and for whom therapies with...
Source: Expert Opinion on Investigational Drugs - September 16, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Remdesivir, a remedy or a ripple in severe COVID-19?
Authors: Doggrell SA Abstract INTRODUCTION: In clinical trial for the Ebola virus, the broad-spectrum anti-viral agent remdesivir was shown to have a good safety profile. Remdesivir is now being tested in severe COVID-19. AREAS COVERED: The Gilead Sciences SIMPLE trial suggests that the short-term use of remdesivir probably does not increase mortality dramatically or have serious short-term toxicity when used to treat severe COVID-19. The Adaptive COVID-19 treatment trials (ACTT1) trial showed that remdesivir may shorten recovery and decrease mortality in severe COVID-19 without increasing adverse effects. ...
Source: Expert Opinion on Investigational Drugs - September 10, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Mavacamten: a novel small molecule modulator of β-cardiac myosin for treatment of hypertrophic cardiomyopathy.
This article reviews available pre-clinical and clinical trials assessing the efficacy and safety of Mavacamten for the treatment of symptomatic obstructive and non-obstructive HCM Expert opinion Findings from Phase 2 and 3 trials suggest that Mavacamten represents a very promising new therapy for the treatment of symptomatic patients with HCM. Treatment leads to an improvement in symptomatic and physiologic metrics for symptomatic patients with HCM with minimal adverse events. Patients with obstructive HCM demonstrated a significant improvement in LVOT gradient, NYHA functional class, Kansas City Cardiomyopathy Questionna...
Source: Expert Opinion on Investigational Drugs - September 10, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Pyoderma gangrenosum: proposed pathogenesis and current use of biologics with an emphasis on complement C5a inhibitor IFX-1.
Authors: Lu JD, Milakovic M, Ortega-Loayza AG, Marzano AV, Alavi A Abstract INTRODUCTION: Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis with no FDA approved treatment. The complement pathway has received renewed attention because it is elevated in inflammatory cutaneous conditions such as hidradenitis suppurativa (HS) and psoriasis. IFX-1 is a complement C5a inhibitor which inhibits neutrophil activation, chemotaxis, and reduces inflammatory signalling and complement driven tissue damage in various diseases. AREAS COVERED: The article discusses a proposed pathogenesis of PG, early clinical investi...
Source: Expert Opinion on Investigational Drugs - September 7, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Targeting pituitary adenylate cyclase-activating polypeptide (PACAP) with monoclonal antibodies in migraine prevention: a brief review.
We examined PubMed, Scopus, and ClinicalTrials.gov electronic databases to examine the relevant material. EXPERT OPINION: There is much proof of the ability of PACAP to cause migraine, but there is limited evidence that blocking PACAP or PAC1 receptor can prevent migraine. However, the potential of anti-PACAP antibodies in migraine prophylaxis is high. Theoretically, if these antibodies block the activation of the trigeminovascular system, they will prevent the onset of migraine attacks. There are still knowledge gaps in the role of PACAP in migraine and the risk/benefit ratio of anti-PACAP antibodies must be carefully...
Source: Expert Opinion on Investigational Drugs - September 4, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

The dawn of targeted therapies for triple negative breast cancer (TNBC): a snapshot of investigational drugs in phase I and II trials.
Authors: Huynh MM, Pambid MR, Jayanthan A, Dorr A, Los G, Dunn SE Abstract Introduction Triple negative breast cancer (TNBC) was once thought to be an insurmountable disease marked by a lack of targeted treatments. However, we are now witnessing the dawn of targeted therapies for TNBC in which progress has stemmed from an improved understanding of the components that make TNBC unique. The identification of biomarkers, such as BRCA1/2, PIK3CA and RSK2, have advanced the field remarkably and there is considerable interest in finding novel therapeutics for TNBC that offer durable clinical benefit with fewer adverse ev...
Source: Expert Opinion on Investigational Drugs - September 3, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Therapeutic strategies for Parkinson's disease: promising agents in early clinical development.
Authors: Fabbri M, Perez-Lloret S, Rascol O Abstract INTRODUCTION: To date, no drug has demonstrated clinically indisputable neuroprotective efficacy in Parkinson's disease (PD). We also have no effective symptomatic treatment for disabling symptoms such as balance problems, and dementia, and we need to improve the efficacy and safety profile of drugs currently used in the management of motor complications. AREAS COVERED: We examine the agents which appear to have most therapeutic promise based on concepts, feasibility in a reasonable time frame, and available clinical data and place an emphasis on disease-modi...
Source: Expert Opinion on Investigational Drugs - August 28, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

New drugs on the horizon for cerebral edema: what's in the clinical development pipeline?
Authors: Robert SM, Reeves BC, Alper SL, Zhang J, Kahle KT Abstract INTRODUCTION: Research has advanced our understanding of the molecular and cellular mechanisms of cerebral edema and has propelled the development of novel anti-edema therapeutics. Current evidence supports aberrant neuro-glial ion transport as a central mechanism that underlies pathological fluid accumulation after central nervous system injury. AREAS COVERED: Novel agents in clinical development show potential in altering the natural history and treatment of cerebral edema. Using the PubMed and Google Scholar databases, we review recent advan...
Source: Expert Opinion on Investigational Drugs - August 23, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Progress in the development of kynurenine and quinoline-3-carboxamide derived drugs.
Authors: Boros FA, Vécsei L Abstract INTRODUCTION: The diverse neuro- and immunomodulatory effects of kynurenine pathway (KP) enzymes and metabolites exert offer possibilities for intervention in diseases such as autoimmunity, neurodegeneration and neoplastic processes. AREAS COVERED: This review focuses on data obtained from to the preclinical and clinical use of a KP metabolite analogue and structurally related compounds. 4-Cl-KYN has completed clinical trials in depression without success. However, the good safety data give hope for further trials in suicide prevention, neuropathic pain and dyskinesia...
Source: Expert Opinion on Investigational Drugs - August 23, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

CD38: Targeted therapy in multiple myeloma and therapeutic potential for solid cancers.
Authors: Jiao Y, Yi M, Xu L, Chu Q, Yan Y, Luo S, Wu K Abstract INTRODUCTION: CD38 is expressed by some cells of hematological malignancies and tumor-related immunosuppressive cells, including regulatory T cells, regulatory B cells, and myeloid-derived suppressor cells. CD38 is an effective target in some hematological malignancies such as multiple myeloma (MM). Daratumumab (Dara), a CD38-targeting antibody, can eliminate CD38high immune suppressor cells and is regarded as a standard therapy for MM because of its outstanding clinical efficacy. Other CD38 monospecific antibodies, such as isatuximab, MOR202, and TAK0...
Source: Expert Opinion on Investigational Drugs - August 23, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Novel therapeutic agents for the treatment of diabetic kidney disease.
Authors: Hartman RE, Rao PSS, Churchwell MD, Lewis SJ Abstract INTRODUCTION: Diabetic Kidney Disease (DKD) involves multifaceted pathophysiology which increases the risk of cardiorenal events and mortality. Conventional therapy is limited to renin-angiotensin aldosterone system inhibition and management of hyperglycemia and hypertension. Recent clinical trials have demonstrated promising nephroprotective effects of antihyperglycemic agents thus modifying guideline treatment recommendations for type 2 diabetic patients with chronic kidney disease. AREAS OF COVERED: Relevant studies and clinical trials were searc...
Source: Expert Opinion on Investigational Drugs - August 18, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Oral Ibrexafungerp: an investigational agent for the treatment of vulvovaginal candidiasis.
We present the chemistry, mechanism of action, pharmacology, microbiology, and results from clinical studies with ibrexafungerp in women with VVC. EXPERT OPINION: Ibrexafungerp addresses several unmet needs with existing antifungal drugs as a first in a new class of antifungal agents with a novel mechanism of action demonstrating no antifungal cross resistance with azoles, and fungicidal activity against Candida spp., including fluconazole-resistant species. Some of the key attributes of ibrexafungerp related to VVC include oral one-day dosing, high tissue penetration, enhanced activity at low pH seen in the vagina, lo...
Source: Expert Opinion on Investigational Drugs - August 13, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Proteasome inhibition for the treatment of glioblastoma.
Authors: Roth P, Mason WP, Richardson PG, Weller M Abstract INTRODUCTION: Glioblastoma is a primary brain tumor with a poor prognosis despite multimodal therapy including surgery, radiotherapy and alkylating chemotherapy. Novel therapeutic options are therefore urgently needed; however, there have been various drug failures in late-stage clinical development. The proteasome represents a key target for anti-cancer therapy as successfully shown in multiple myeloma and other hematologic malignancies. AREAS COVERED: This review article summarizes the preclinical and clinical development of proteasome inhibitors in ...
Source: Expert Opinion on Investigational Drugs - August 13, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

An expert overview of emerging therapies for acute myeloid leukemia: novel small molecules targeting apoptosis, p53, transcriptional regulation and metabolism.
Authors: Saxena K, Konopleva M Abstract INTRODUCTION: Acute myeloid leukemia (AML) is an aggressive malignancy of clonal myeloid precursor cells. Curative therapy has classically involved the use of intensive induction chemotherapy followed by consolidation with additional chemotherapy or allogeneic hematopoietic stem cell transplant. For many patients, such an approach is prohibitive because of high treatment-related toxicities. Advancements in the molecular understanding of AML have led to the introduction of new targeted therapies that are changing the treatment landscape for AML. AREAS COVERED: We review em...
Source: Expert Opinion on Investigational Drugs - August 13, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Systemic lupus erythematosus: an expert insight into emerging therapy agents in preclinical and early clinical development.
Authors: Tocut M, Schoenfeld Y, Zandman-Goddard G Abstract INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic disease that is potentially fatal. There is no cure for SLE and the medications used are associated with toxic side effects. In the era of revolutionary emerging novel biologic agents, the design and investigation of targeted therapy for these patients is necessary. Novel therapies under investigation in phase II-III clinical trials showed promising results. Therapies can target various pathways involved in SLE including cytokines, signal transduction inhibitors, B cell depletion and interference...
Source: Expert Opinion on Investigational Drugs - August 13, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Inhibition of Bruton ´s tyrosine kinase as a novel therapeutic approach in multiple sclerosis.
Inhibition of Bruton´s tyrosine kinase as a novel therapeutic approach in multiple sclerosis. Expert Opin Investig Drugs. 2020 Aug 08;: Authors: Torke S, Weber MS Abstract Introduction: B cells have increasingly come under the spotlight as mediators of inflammatory central nervous system (CNS) demyelinating diseases such as multiple sclerosis (MS). B cell depletion via the targeting of the surface molecule CD20 has proven to be highly effective, however, continuous absence of an integral component of the immune system may cause safety concerns over time. Declining humoral competence and potential...
Source: Expert Opinion on Investigational Drugs - August 13, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Abrocitinib: A potential treatment for moderate-to-severe atopic dermatitis.
Authors: Nezamololama N, Crowley EL, Gooderham MJ, Papp K Abstract INTRODUCTION: Atopic dermatitis (AD) is a common and debilitating dermatosis that often impacts the physical and psychological quality of life in children and adults. A limited number of treatment options are available for AD, and often these treatments result in an insufficient response or may be contraindicated for some patients. This treatment gap creates an increasing demand for alternative AD therapies. The Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway is known to play a critical role in the dysregulation ...
Source: Expert Opinion on Investigational Drugs - August 4, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Antisense oligonucleotide therapeutics in clinical trials for the treatment of inherited retinal diseases.
Authors: Xue K, MacLaren RE Abstract Introduction Antisense oligonucleotides (ASOs) represent a class of drugs which can be rationally designed to complement the coding or non-coding regions of target RNA transcripts. They could modulate pre-messenger RNA splicing, induce mRNA knockdown or block translation of disease-causing genes, thereby slowing disease progression. The pharmacokinetics of intravitreal delivery may enable ASOs to be effective in the treatment of inherited retinal diseases. Areas covered We review the current status of clinical trials of ASO therapies for inherited retinal diseases, which have de...
Source: Expert Opinion on Investigational Drugs - August 4, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Cystic fibrosis - Ten promising therapeutic approaches in the current era of care.
Authors: Somayaji R, Nichols D, Bell SC Abstract INTRODUCTION: Cystic fibrosis (CF) is a genetic disease affecting multiple organ systems. Research and innovations in novel therapeutic agents and health care delivery have resulted in dramatic improvements in quality of life and survival for people with CF. Despite this, significant disease burden persists for many and this is compounded by disparities in treatment access and care which globally necessitates further work to improve outcomes. Because of the advent of a numerous therapies which includes gene-targeted modulators in parallel with specialized care delive...
Source: Expert Opinion on Investigational Drugs - August 4, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Huntingtin-lowering strategies for Huntington's disease.
Authors: Barker RA, Fujimaki M, Rogers P, Rubinsztein DC Abstract INTRODUCTION: Huntington's disease (HD) is an incurable, autosomal dominant neurodegenerative disease caused by an abnormally long polyglutamine tract in the huntingtin protein. Because this mutation causes disease via gain-of-function, lowering huntingtin levels represents a rational therapeutic strategy. AREAS COVERED: We searched MEDLINE, CENTRAL and other trial databases, and relevant company and HD funding websites for press releases until April 2020 to review strategies for huntingtin lowering, including autophagy and PROTACs, which have be...
Source: Expert Opinion on Investigational Drugs - August 4, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Phase I clinical trial of KML001 monotherapy in patients with advanced solid tumors.
CONCLUSIONS: Doses equal to or greater than 10 mg/day KML001 alone were tolerable and produced plasma concentrations higher than biologically relevant targets. PMID: 32735765 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - August 1, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Baricitinib: therapeutic potential for moderate to severe atopic dermatitis.
Authors: Calabrese L, Malvaso D, Chiricozzi A, Tambone S, D'Urso DF, Guerriero C, Peris K Abstract INTRODUCTION: . Atopic dermatitis (AD) is a chronic inflammatory skin disease mediated by multiple signals including janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. Current therapeutic armamentarium consists of a limited number of drugs which may result in the insufficient management of AD. Preclinical evidence regarding inhibition of JAK/STAT led to the development of a promising class of therapeutics, namely, JAK inhibitors. Baricitinib, a novel JAK1/JAK2 inhibitor is currently un...
Source: Expert Opinion on Investigational Drugs - July 28, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Polatuzumab vedotin: an investigational anti-CD79b antibody drug conjugate for the treatment of diffuse large B-cell lymphoma.
Authors: Bourbon E, Salles G Abstract INTRODUCTION: New agents for the management of B-cell non-Hodgkin lymphomas (NHLs) are needed, particularly for high-risk and relapsed or refractory patients. Antibody-drug conjugates (ADCs) provide targeted drug delivery to tumors with a broader therapeutic index of cytotoxic agent thus reducing their systemic toxicity while increasing intracellular concentrations. Among them, polatuzumab vedotin, an anti-CD79b conjugated to the microtubule inhibitor monomethyl auristatin E (MMAE) raises particular interest. AREAS COVERED: We discuss the pharmacological development of pola...
Source: Expert Opinion on Investigational Drugs - July 25, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Type I interferon antagonists in clinical development for lupus.
Authors: Paredes JL, Niewold TB Abstract INTRODUCTION: Systemic lupus erythematosus (SLE) is a severe chronic and incurable autoimmune disease. Treatment includes glucocorticoids and small molecule immunosuppressants which typically result in partial responses, and hence there is a great need for new therapies. The type I interferon (IFN) pathway is activated in more than 50% of SLE patients, and it is strongly implicated as a pathogenic factor in SLE. A number of therapeutics have been developed to target type I IFN in SLE. AREAS COVERED: We searched the literature using "SLE and interferon antagonists&qu...
Source: Expert Opinion on Investigational Drugs - July 25, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Trastuzumab-deruxtecan: an investigational agent for the treatment of HER2-positive breast cancer.
This article reviews preclinical and clinical data on T-DXd. A systematic literature search was performed to identify relevant publications. The search included original research articles, abstracts from major conferences, and reviews and was limited to English-language publications. EXPERT OPINION: T-DXd is an efficacious and tolerable drug and harbors promise as a key addition to the therapeutic field in HER2-positive breast cancer. PMID: 32701032 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - July 25, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Givinostat: an emerging treatment for polycythemia vera.
We present an overview of PV, current treatment guidelines, and the putative mechanism(s) of action of givinostat. We discuss the preclinical and clinical studies of givinostat in PV and briefly review approved and investigational competitor compounds. EXPERT OPINION: HDAC inhibitors have long been known to be active in PV, but chronic toxicities can be challenging. Givinostat, however, is active and well tolerated, and is entering a pivotal Phase III randomized trial. Givinostat offers the possibility of replacing hydroxyurea as the standard first-line cytoreductive choice for PV patients. This would completely c...
Source: Expert Opinion on Investigational Drugs - July 24, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Anti-Integrin therapy for retinovascular diseases.
Authors: Bhatwadekar AD, Kansara V, Luo Q, Ciulla T Abstract INTRODUCTION: Integrins are a family of multi-functional cell-adhesion molecules heterodimeric receptors that connect extracellular matrix (ECM) to actin in the cell cortex, thus regulating cellular adhesion, migration, proliferation, invasion, survival, and apoptosis. Consequently, integrins play a role in inflammation, angiogenesis and fibrosis. AREAS COVERED: This review examines each anti-integrin agent in terms of its chemical nature, route of administration, and anti-integrin action. It also provides a summary of preclinical and clinical studies...
Source: Expert Opinion on Investigational Drugs - July 15, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Discontinued disease-modifying therapies for Alzheimer's disease: status and future perspectives.
This article reviews key drugs that have been discontinued while in development for AD and delineates the future landscape for present and alternative approaches. EXPERT OPINION: Anti-Aβ drugs have failed to validate the Aβ cascade hypothesis of AD. Early findings suggest that the same is happening with therapeutics targeting tau and focussing future research solely on anti-tau drugs is inappropriate. Alternative targets should be pursued, including apolipoprotein E, immunomodulation, plasma exchange, protein autophagy and clearance, mitochondrial dysfunction, abnormal glucose metabolism, neurovascular unit s...
Source: Expert Opinion on Investigational Drugs - July 15, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Dopamine β hydroxylase as a potential drug target to combat hypertension.
Dopamine β hydroxylase as a potential drug target to combat hypertension. Expert Opin Investig Drugs. 2020 Jul 13;: Authors: Dey SK, Saini M, Prabhakar P, Kundu S Abstract INTRODUCTION: Despite a large number of commercially available drugs, hypertension and related cardiovascular diseases remain a global problem. It is thus imperative that novel drugs and therapeutic strategies are regularly identified, and alternative targets explored. Dopamine β hydroxylase (DBH), a key player in the catecholamine biosynthetic pathway, may provide a therapeutic opportunity and should be extensively explore...
Source: Expert Opinion on Investigational Drugs - July 15, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Innovative therapies for invasive fungal infections in preclinical and clinical development.
Authors: Yu Y, Albrecht K, Groll J, Beilhack A Abstract INTRODUCTION: The incidence of life-threatening invasive fungal infections (IFIs) has increased significantly in recent years. Current therapeutic options for IFIs are limited. Only four major classes of antifungal agents are available to clinicians, namely polyenes, azoles, echinocandins, and flucytosine. These antifungals have particular drawbacks, including toxicity, drug-drug interactions, and increasing antifungal resistance. Consequently, there is an urgent need for new antifungals to combat IFIs. AREAS COVERED: This review illuminates new classes of...
Source: Expert Opinion on Investigational Drugs - July 15, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

New immunotherapeutic drugs in advanced non-small cell lung cancer (NSCLC): from preclinical to phase I clinical trials.
Authors: Rocco D, Gregorc V, Della Gravara L, Lazzari C, Palazzolo G, Gridelli C Abstract INTRODUCTION: The development of immune checkpoint inhibitors (ICI) has represented a revolution in the treatment of non-small cell lung cancer (NSCLC) and has established a new standard of care for different settings. However, through adaptive changes, cancer cells can develop resistance mechanisms to these drugs, hence the necessity for novel immunotherapeutic agents. AREAS COVERED: This paper explores the immunotherapeutics currently under investigation in phase I clinical trials for the treatment of NSCLC as monotherap...
Source: Expert Opinion on Investigational Drugs - July 11, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Emerging agents for the treatment of Chagas disease: what is in the preclinical and clinical development pipeline?
Authors: Martínez-Peinado N, Cortes-Serra N, Losada-Galvan I, Alonso-Vega C, Urbina JA, Rodríguez A, VandeBerg JL, Pinazo MJ, Gascon J, Alonso-Padilla J Abstract INTRODUCTION: Chagas disease treatment relies on the lengthy administration of benznidazole and/or nifurtimox, which have frequent toxicity associated. The disease, caused by the parasite Trypanosoma cruzi, is mostly diagnosed at its chronic phase when life-threatening symptomatology manifest in approximately 30% of those infected. Considering that both available drugs have variable efficacy by then, and there are over 6 million people infect...
Source: Expert Opinion on Investigational Drugs - July 9, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

A randomized phase I clinical trial comparing the pharmacokinetic, safety, and immunogenicity of potential biosimilar recombinant human HER2 monoclonal antibody for injection and trastuzumab in healthy Chinese adults.
Authors: Wang J, Niu S, Dong W, Wei L, Ou L, Zhang T, Zhang L, Nie X, Wang Q, Shen T, Wang Q, Xia L, Liu G, Jin J, Zheng Q, Song H, Fang Y Abstract OBJECTIVES: Recombinant human HER2 monoclonal antibody for injection (AK-HER2) is a potential biosimilar of trastuzumab (Herceptin®). This phase Ⅰ study aimed to demonstrate the pharmacokinetic (PK) equivalence between AK-HER2 and trastuzumab in healthy volunteers. Besides, safety and immunogenicity were investigated. RESEARCH DESIGN AND METHODS: This was a randomized, double-blind phase Ⅰ trial in 96 healthy adults who received a single intravenous infusion...
Source: Expert Opinion on Investigational Drugs - July 2, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Enhancing venetoclax activity in hematological malignancies.
Authors: Satta T, Grant S Abstract Introduction: Targeting anti-apoptotic pathways involving the BCL2 family proteins represents a novel treatment strategy in hematologic malignancies. Venetoclax, a selective BCL2 inhibitor, represents the first approved agent of this class, and is currently used in CLL and AML. However, monotherapy is rarely sufficient for sustained responses due to development of drug resistance and loss of dependence upon the targeted protein. Numerous pre-clinical studies have shown that combining venetoclax with other agents may represent a more effective therapeutic strategy by circumventing ...
Source: Expert Opinion on Investigational Drugs - July 2, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Bempedoic acid, an inhibitor of ATP citrate lyase for the treatment of hypercholesterolemia: early indications and potential.
Authors: Brandts J, Ray KK Abstract INTRODUCTION: The lowering of low-density lipoprotein cholesterol (LDL-C), regardless of the method used, results in a reduction of cardiovascular events. Bempedoic acid is a new and until now, the only approved adenosine triphosphate citrate lyase inhibitor that works through the cholesterol-synthesis pathway (similar to statins) that leads to a safe and effective reduction in LDL-C. AREAS COVERED: We review clinical phase 2 and 3 studies on bempedoic acid's lipid-lowering effect and approved indications. EXPERT OPINION: In the United States, bempedoic acid is currently ...
Source: Expert Opinion on Investigational Drugs - June 24, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

TP53 dysfunction in chronic lymphocytic leukemia: clinical relevance in the era of B-cell receptors and BCL-2 inhibitors.
Authors: Morabito F, Gentile M, Monti P, Recchia AG, Menichini P, Skafi M, Atrash M, De Luca G, Bossio S, Al-Janazreh H, Galimberti S, Salah Z, Morabito L, Mujahed A, Hindiyeh M, Dono M, Fais F, Cutrona G, Neri A, Tripepi G, Fronza G, Ferrarini M Abstract INTRODUCTION: . Patients with TP53 dysfunction, assessed by del(17p) or TP53 mutations, respond poorly to chemo-immunotherapy and fare better with the new therapies (BCR and BCL-2 inhibitors); however, it is unclear whether their response is similar to that of patients without anomalies or whether there is currently an adequate determination of TP53 dysfunction. ...
Source: Expert Opinion on Investigational Drugs - June 21, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Bile acid modulators for the treatment of nonalcoholic steatohepatitis (NASH).
This article evaluates the efficacy and pitfalls of GPBAR1 and FXR-based therapies in the treatment of NASH. While there are no GPBAR1 agonist in clinical development, several FXR ligands have completed phase 2 and phase 3 trials in NASH. EDP305, tropifexor, cilofexor, nidufexor, TERN.101, Px-104, EYP001, MET409. Individual FXR agonists have shown variable efficacy in reversing liver steatohepatitis and fibrosis. Class-related, dose-dependent side effects: pruritus, increased plasma levels of cholesterol and LDLc, and reduction of HDL have been reported. EXPERT OPINION: Efficacy of FXR agonists as stand-alone therapy i...
Source: Expert Opinion on Investigational Drugs - June 21, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Novel agents for the treatment of polycythemia vera: an insight into preclinical research and early phase clinical trials.
This article reviews the current data from completed early phase clinical trials in PV, either as monotherapy or in combination with the few currently approved agents. EXPERT OPINION: There remains an opportunity in PV management to improve efficacy and decrease risk of disease progression. Evolving data from use of long acting interferons are serving to clarifying the potential front line role of this therapy. JAK2 inhibition has made a significant impact on decreasing morbidity in patients with hydroxyurea resistant/refractory disease. New approaches may soon expand options including histone deactylase inhibitors (HD...
Source: Expert Opinion on Investigational Drugs - June 21, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Shedding light on developmental drugs for idiopathic pulmonary fibrosis.
Authors: Spagnolo P, Bonella F, Ryerson CJ, Tzouvelekis A, Maher TM Abstract INTRODUCTION: . Idiopathic pulmonary fibrosis (IPF) is an age-related disease of unknown cause. The disease is characterized by relentless scarring of the lung parenchyma resulting in respiratory failure and death. Two antifibrotic drugs (pirfenidone and nintedanib) are approved for the treatment of IPF worldwide, but they do not offer a cure and are associated with tolerability issues. Owing to its high unmet medical need, IPF is an area of dynamic research activity. AREAS COVERED: . There is a growing portfolio of novel therapies tha...
Source: Expert Opinion on Investigational Drugs - June 18, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Prexasertib: an investigational checkpoint kinase inhibitor for the treatment of high-grade serous ovarian cancer.
This article reviews the available data on the pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of prexasertib in the treatment of HGSOC. Expert opinion Until now, prexasertib demonstrated clinical activity in phase I and II clinical trial for treating wild-type BRCA HGSOC, whereas its promising efficacy as monotherapy and combined with olaparib in BRCA-mutated HGSOC has been preliminary evidenced only in phase I studies. Compared to other drugs of the same class, prexasertib showed a better tolerability profile, causing moderate hematological toxicity. Further studies are needed to confirm efficacy and sa...
Source: Expert Opinion on Investigational Drugs - June 18, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Current and experimental drug therapy for the treatment of polycystic ovarian syndrome.
Authors: Della Corte L, Foreste V, Barra F, Gustavino C, Alessandri F, Centurioni MG, Ferrero S, Bifulco G, Giampaolino P Abstract INTRODUCTION: Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 8-13% of reproductive-age women. Irregular periods, hirsutism, or infertility are the most common clinical presentations of patients affected by PCOS. This syndrome is also linked to metabolic abnormalities such as type 2 diabetes, insulin resistance and obesity. The optimal therapeutic approach is still unknown. AREAS COVERED: This narrative review offers an overview of the literature on current an...
Source: Expert Opinion on Investigational Drugs - June 18, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Therapeutic peptides for the treatment of systemic lupus erythematosus: a place in therapy.
Authors: Talotta R, Atzeni F, Laska MJ Abstract INTRODUCTION: Studies in vitro and in vivo have identified several peptides that are potentially useful in treating systemic lupus erythematosus (SLE). The rationale for their use lies in the cost-effective production, high potency, target selectivity, low toxicity and a peculiar mechanism of action that is mainly based on the induction of immune tolerance. Three therapeutic peptides have entered clinical development, but they have yielded disappointing results. However, some subsets of patients, such as those with positivity of anti-dsDNA antibodies, appear more like...
Source: Expert Opinion on Investigational Drugs - June 7, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Does lopinavir measure up in the treatment of Covid-19?
Authors: Doggrell SA Abstract INTRODUCTION: Lopinavir in combination with ritonavir is approved for the treatment of HIV and has recently been subject to a clinical trial in severe Covid-19. AREAS COVERED: This evaluation is of LOTUS China (the Lopinavir Trial for Suppression of SARS-Cov-2 in China), which was a randomised trial in hospitalised subjects with Covid-9 in a respiratory sample and pneumonia. As, in severe Covid-19, lopinavir/ritonavir had no beneficial effects but increased gastrointestinal adverse effects, this combination should not be used at this stage of Covid-19. EXPERT OPINION: In my opi...
Source: Expert Opinion on Investigational Drugs - June 2, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Selective androgen receptor modulators (SARMs) as pharmacological treatment for muscle wasting in ongoing clinical trials.
Authors: Fonseca GWPD, Dworatzek E, Ebner N, von Haehling S Abstract INTRODUCTION: Skeletal muscle wasting is a frequent clinical problem encountered in patients with chronic diseases. Its development seems to share a common pathway, characterized by increased levels of inflammatory markers, an imbalance between muscle protein synthesis and degradation, and atrophy from disuse. Although testosterone has long been proposed as a treatment for patients with muscle wasting, undesirable side effects have raised concerns about prostatic hypertrophy in men as well as virilization in women. Selective androgen receptor modu...
Source: Expert Opinion on Investigational Drugs - June 2, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors: A Paradigm Shift for Treatment of Anemia in Chronic Kidney Disease?
Authors: Souza E, Cho KH, Harris ST, Flindt NR, Watt RK, Pai AB Abstract INTRODUCTION: The hypoxia-inducible factor prolyl hydroxylase (HIF-PH) pathway is responsible for regulating the biosynthesis of erythropoietin (EPO) and maintaining iron homeostasis. Investigational drugs that target the HIF-PH pathway are promising alternatives for treating anemia in Chronic Kidney Disease (CKD). Areas covered: This review summarizes recent advances focused on the clinical development of HIF-PH inhibitors (HIF-PHIs) as potentially novel therapies in the treatment of anemia in CKD based on publications available on PubMed and...
Source: Expert Opinion on Investigational Drugs - June 2, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Abicipar pegol: an investigational anti-VEGF agent for the treatment of wet age-related macular degeneration.
Authors: Ferro Desideri L, Traverso CE, Nicolò M Abstract INTRODUCTION: Several approaches have been investigated for the management of wet age-related macular degeneration (w-AMD); however, the first-line treatment option for w-AMD currently constitutes anti-VEGF agents. Abicipar pegol is a designed ankyrin repeat protein (DARPin), a novel, promising anti-VEGF agent for the treatment of w-AMD and is reviewed in this article. AREAS COVERED: We discuss the pharmacokinetic, pharmacodynamic, clinical, and tolerability profile revealed by phase II REACH, CYPRESS, and BAMBOO and phase III CEDAR and SEQUOIA Tr...
Source: Expert Opinion on Investigational Drugs - June 2, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Pamrevlumab for the treatment of idiopathic pulmonary fibrosis.
Authors: Sgalla G, Franciosa C, Simonetti J, Richeldi L Abstract INTRODUCTION: The two available therapies for idiopathic pulmonary fibrosis (IPF), pirfenidone and nintedanib, slow down but do not halt IPF progression. Hence, in the last few years, several agents with specific molecular targets have been investigated to find a cure for IPF. Pamrevlumab, a recombinant human antibody that binds to connective tissue growth factor (CTGF) has emerged as a potential therapy for IPF and has advanced to phase 3 clinical trials. Because CTGF plays a central role in tumorigenesis and abnormal tissue repair processes, this co...
Source: Expert Opinion on Investigational Drugs - May 26, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

BIO 300: a promising radiation countermeasure under advanced development for acute radiation syndrome and the delayed effects of acute radiation exposure.
We present the current status of a promising radiation countermeasure, BIO 300 (a genistein-based agent), that has been extensively investigated in murine models of H-ARS and models of the delayed effects of acute radiation exposure (DEARE) and is currently being evaluated in large animal models. It is also being developed for the prevention of radiation-induced toxicities associated with solid tumor radiotherapy and is the subject of two active Investigational New Drug (IND) applications. We have included a listing and brief review of significant investigations of this promising medical countermeasure. EXPERT OPINION:...
Source: Expert Opinion on Investigational Drugs - May 26, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research