Oregovomab: an investigational agent for the treatment of advanced ovarian cancer.
Authors: Pietragalla A, Duranti S, Daniele G, Nero C, Ciccarone F, Lorusso D, Fagotti A, Scambia G Abstract Introduction: Ovarian cancer (OC) represents the leading cause of death among gynecological cancers. Despite novel compound classes like vascular endothelial growth factor (VEGF) inhibitors or poly-ADP ribose polymerase (PARP) inhibitors are available, which improve significantly efficacy of platinum-based chemotherapy, OC prognosis remains poor and innovative strategies are needed. The induction of tumor specific immune response with a therapeutic intent is a very challenging approach. Oregovomab is a murine...
Source: Expert Opinion on Investigational Drugs - January 12, 2021 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

The time to develop treatments for diabetic neuropathy.
Authors: Rendell MS Abstract BACKGROUND: Diabetic neuropathy is a multifaceted condition affecting up to 50% of individuals with long standing diabetes. The most common presentation is peripheral diabetic sensory neuropathy (DPN). METHODS: We carried out a systematic review of papers dealing with diabetic neuropathy on Pubmed in addition to a targeted Google search.Search terms included small fiber neuropathy,diffuse peripheral neuropathy, quantitative sensory testing, nerve conduction testing, intra-epidermal nerve fiber density, corneal confocal reflectance microscopy, aldose reductase inhbitors, nerve growth...
Source: Expert Opinion on Investigational Drugs - January 12, 2021 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Trabodenoson and trabecular meshwork rejuvenation: A comprehensive review of clinical data.
This article sheds light on the root causes of the two pivotal Phase 3 clinical trials failures in patients with POAG or OH; it further highlights the discovery of MMP-2 in trabecular meshwork (TM) rejuvenation, which has strategic importance in long-term glaucoma patient care. EXPERT OPINION: Trabodenoson is a BID glaucoma eye drop with possible QD dose as maintenance. Its Phase 3 pivotal clinical trials failed at the wrong dose and dosing regimen because of the misinterpretation of the complex IOP results from the Phase 2 monotherapy and combination studies. The future development should focus on the TM benefits whil...
Source: Expert Opinion on Investigational Drugs - January 8, 2021 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Safety, Pharmacokinetics, and Pharmacodynamics of TQ-A3334, an Oral Toll-Like Receptor 7 Agonist, in Healthy Individuals.
CONCLUSIONS: Oral doses of 0.2-1.8 mg appeared to be safe and tolerated. PD activity was seen at doses ranging from 1.0 to 1.8 mg, indicating its possible future use to treat CHB. PMID: 33405993 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - January 8, 2021 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Developing DMD therapeutics: a review of the effectiveness of corticosteroids, stop-codon readthrough, and exon-skipping therapies.
Authors: Sheikh O, Yokota T Abstract INTRODUCTION: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by mutations in the dystrophin (DMD) gene. Most patients die from respiratory failure or cardiomyopathy. There are significant unmet needs for treatments for DMD because the standard of care is principally limited to symptom relief through treatments such as steroids. AREAS COVERED: This review summarizes safety and efficacy in promising areas of DMD therapeutics - steroids, stop codon readthrough, gene replacement therapy, and exon-skipping - under clinical examination from 2015-2020 as...
Source: Expert Opinion on Investigational Drugs - January 5, 2021 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

The design and analysis of non-randomized studies: A case study of off-label use of hydroxychloroquine in the COVID-19 pandemic.
This article focuses on several key design and analysis considerations that can improve the scientific rigor of non-randomized studies of off-label drugs. Areas covered The aim of this article is to provide an overview of best approaches that should be considered for non-randomized studies on off-label drugs. In this article, we discuss these approaches in detail and use a non-randomized study by Rivera et al. in Cancer Discovery, which analyzed factors associated with off-label treatments for COVID-19 and their potential impact on 30-day all-cause mortality among cancer and SARS-CoV-2 infected patients, as an example of m...
Source: Expert Opinion on Investigational Drugs - December 29, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Selective endothelin A receptor antagonism in patients with proteinuric chronic kidney disease.
Authors: Provenzano M, Andreucci M, Garofalo C, Minutolo R, Serra R, De Nicola L Abstract INTRODUCTION: Selective antagonists of Endothelin-1 receptors (ERA) have been tested in diabetic and nondiabetic chronic kidney disease (CKD). The SONAR trial (Study Of diabetic Nephropathy with AtRasentan) was the first randomized, phase 3, study assessing the long-term effect of ERA on CKD progression. AREAS COVERED: We examine the ERA effects in proteinuric CKD. We discuss the results of the main clinical studies on ERA in CKD and offer an opinion on the findings of SONAR study and future perspectives in this field. We ...
Source: Expert Opinion on Investigational Drugs - December 29, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Cardiac fibrosis: emerging agents in preclinical and clinical development.
Authors: Spoladore R, Falasconi G, Fiore G, Di Maio S, Preda A, Slavich M, Margonato A, Fragass G Abstract INTRODUCTION: Myocardial fibrosis is a remarkably dynamic process mediated by different molecular pathways that represent potential targets of novel therapeutic interventions. Transforming Growth Factor-beta (TGF-β), connective Tissue Growth Factor (cTGF) and Galectin-3 (Gal-3) represent the most promising targets on which research has been currently focusing. AREA COVERED: This review initially discusses those drugs used in clinical practice for their anti-fibrotic properties and later examines emerg...
Source: Expert Opinion on Investigational Drugs - December 29, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Tackling type 2 diabetes-associated cardiovascular and renal comorbidities: a key challenge for drug development.
Authors: Adeghate EA, Kalász H, Al Jaberi S, Adeghate J, Tekes K PMID: 33327794 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - December 19, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Targeting the Tumor Microenvironment in Cholangiocarcinoma: Implications for Therapy.
Authors: Wang J, Ilyas S Abstract Introduction Cholangiocarcinomas (CCAs) are biliary epithelial tumors with rising incidence over the past 3 decades. Early diagnosis of CCAs remains a significant challenge and the majority of patients present at an advanced stage. CCAs are heterogeneous tumors and currently available standard systemic therapy options are of limited effectiveness. Immune checkpoint inhibition (ICI) has transformed cancer therapy across a spectrum of malignancies. However, the response rate to ICI has been relatively disappointing in CCAs owing to its desmoplastic tumor microenvironment (TME). Areas...
Source: Expert Opinion on Investigational Drugs - December 18, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Nivolumab: an investigational agent for the treatment of biliary tract cancer.
Authors: Di Federico A, Rizzo A, Ricci AD, Frega G, Palloni A, Tavolari S, Brandi G Abstract INTRODUCTION: Biliary tract cancers (BTCs) include four uncommon primary biliary malignancies characterized by poor prognosis: intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer. To date, the available therapeutic options are limited; nevertheless, with the advent of targeted therapy and immunotherapy, the treatment scenario is constantly changing, opening towards future possibilities for the personalized treatment of BTC. Among these treatments, nivolumab is cu...
Source: Expert Opinion on Investigational Drugs - December 16, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Infigratinib (BGJ398): An investigational agent for the treatment of FGFR-altered intrahepatic cholangiocarcinoma.
Authors: Botrus G, Raman P, Oliver T, Bekaii-Saab T Abstract INTRODUCTION: The fibroblast growth factor receptor (FGFR) pathway is essential in cell proliferation, differentiation, migration and survival. Cancers such as intrahepatic cholangiocarcinoma (IHCA) have demonstrated alterations of FGFR allowing unregulated growth and spread. Infigratinib (BGJ398) is a potent ATP-competitive inhibitor of all four FGFR receptors as demonstrated by the consistent high prevalence of hyperphosphatemia, indicating disruption of FGFR-related phosphate homeostasis. AREAS COVERED: In this article, the authors discuss preclini...
Source: Expert Opinion on Investigational Drugs - December 16, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Susan Pandya on investigational treatment approaches to cholangiocarcinoma.
Authors: Pandya S PMID: 33302739 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - December 12, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Results from a biomarker study to accompany a phase II trial of RRx-001 with reintroduced platinum-based chemotherapy in relapsed small cell carcinoma.
CONCLUSION: During treatment with RRx-001, reduced expression of the protumorigenic M2 marker CD206 on peripheral monocytes positively correlated with increased response and survival. PMID: 33306414 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - December 12, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Safety and pharmacokinetics of a biosimilar of denosumab (KN012): Phase 1 and bioequivalence study in healthy Chinese subjects.
CONCLUSION: The PK characteristics were comparable for the denosumab biosimilar and denosumab groups. Their safety profiles were also similar. TRIAL REGISTRATION: : The trial is registered at the Chinese Clinical Trial website (http://www.chinadrugtrials.org.cn/index.html #CTR20181231). PMID: 33306418 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - December 12, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Investigational drugs for the treatment of diffuse large B-cell lymphoma.
Authors: Patriarca A, Gaidano G Abstract Introduction: Diffuse large B cell lymphoma (DLBCL) is the most frequent lymphoma in adults. 30-40% DLBCL eventually relapse and 10% are primary refractory, posing an unmet clinical need, especially in patients not eligible for hematopoietic stem cell transplant. Knowledge of DLBCL molecular pathogenesis has identified druggable molecular pathways. Surface antigens can be targeted by novel antibodies and innovative cell therapies. Areas covered: This review illuminates those investigational drugs and cell therapies that are currently in early phase clinical trials for the tr...
Source: Expert Opinion on Investigational Drugs - December 11, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Investigational drugs in early phase development for biliary cholangitis.
Authors: Gochanour EM, Kowdley KV Abstract Introduction: With a large percentage of patients having an incomplete response or intolerance to current FDA approved medications, new therapies for the treatment of primary biliary cholangitis are in great demand. Areas covered: In this review, we assess currently available drugs as well as promising new therapies for the treatment of primary biliary cholangitis. A literature search was performed with the following search terms: "PBC treatment", "PBC therapeutics", "PBC clinical trials" and included original articles, meta-analyses, and syst...
Source: Expert Opinion on Investigational Drugs - December 3, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Systemic therapy of advanced/metastatic gastrointestinal stromal tumours: an update on progress beyond imatinib, sunitinib and regorafenib.
Authors: Mohammadi M, Gelderblom H Abstract Introduction Discovery of oncogenic mutations in the KIT and PDGFRA tyrosine kinase receptor was a crucial step for development of tyrosine kinase inhibitors (TKI's). Since then, GIST became a model for development of molecular targeted therapy, which led to dramatically improved median overall survival of advanced GIST . Still further progress is needed after third line or for TKI resistant mutations. Areas covered In this review, after a brief introduction of imatinib, sunitinib an regorafenib an overview of TKI's that were evaluated beyond these drugs is provided, with...
Source: Expert Opinion on Investigational Drugs - December 3, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Adrecizumab: an investigational agent for the biomarker-guided treatment of sepsis.
Authors: Deniau B, Takagi K, Asakage A, Mebazaa A Abstract INTRODUCTION: sepsis is a major health problem with a high incidence and mortality. ADM, a free-circulating peptide mainly expressed and secreted by vascular endothelial cells, shows vasodilatory properties and causes hypotension when present in higher concentrations during sepsis. AREAS COVERED: Adrecizumab (ADZ) (HAM 8101) is a humanized targeted therapy directed against the N-terminus of adrenomedullin (ADM). ADZ inhibits excessive circulating sepsis-induced ADM and stimulates protective effects on the endothelial barrier, and decreases interstitial ...
Source: Expert Opinion on Investigational Drugs - December 3, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

A Phase I, Randomized, Double-Blind, Single-Dose, Parallel-Group Study to compare Pharmacokinetic Similarity, Safety, and Immunogenicity Between BAT2506 and Golimumab in Healthy Chinese Male Subjects.
Conclusions: Our study confirmed the PK similarity between BAT2506 and golimumab, and showed good tolerance of BAT2506 in healthy subjects. There were no differences in safety and immunogenicity between the two drugs. Therefore, BAT2506 meets the criteria for biosimilarity to golimumab. Trial registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04152759). PMID: 33241960 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - November 28, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

The impact of molecular profiling on cholangiocarcinoma clinical trials and experimental drugs.
Authors: Sipra QUAR, Shroff R PMID: 33228417 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - November 26, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Cholangiocarcinoma: Bridging the translational gap from preclinical to clinical development and implications for future therapy.
Authors: Baiocchi L, Sato K, Ekser B, Kennedy L, Francis H, Ceci L, Lenci I, Alvaro D, Franchitto A, Onori P, Gaudio E, Wu C, Chakraborty S, Glaser S, Alpini G Abstract INTRODUCTION: Cholangiocarcinoma (CCA) is a devastating liver tumor with a poor prognosis. While less than 50% of patients with CCA may benefit from surgical resection, the rest undergoes chemotherapy with disappointing results (mean survival
Source: Expert Opinion on Investigational Drugs - November 25, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Experimental HER2 targeted therapies for biliary tract cancer.
Authors: Rizzo A, Ricci AD, Bonucci C, Tober N, Palloni A, Frega G, Brandi G Abstract Introduction Biliary tract cancers (BTCs) constitute a heterogeneous group of poor-prognosis solid tumors with limited treatment options. In the last decade, global efforts have tried to identify therapeutic targets by genomic profiling of BTC, unveiling several genetic aberrations that could play a prognostic and/or a predictive role in these malignancies. Areas covered In this review, we will present an overview regarding the role of HER2 targeted therapies in BTC, with a particular focus on clinical studies carried out in this ...
Source: Expert Opinion on Investigational Drugs - November 22, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Recent progress in development of cyclin-dependent kinase 7 inhibitors for cancer therapy.
Authors: Liang H, Du J, Elhassan RM, Hou X, Fang H Abstract Introduction: Cyclin-dependent kinase 7 (CDK7) is a part of the CDK-activating kinase family (CAK) which has a key role in the cell cycle and transcriptional regulation. Several lines of evidence suggest that CDK7 is a promising therapeutic target for cancer. CDK7 selective inhibitors such as SY-5609 and CT7001 are in clinical development. Areas covered: We explore the biology of CDK7 and its role in cancer and follow this with an evaluation of the preclinical and clinical progress of CDK7 inhibitors, and their potential in the clinic. We searched PubMed a...
Source: Expert Opinion on Investigational Drugs - November 18, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

AE37: a HER2-targeted vaccine for the prevention of breast cancer recurrence.
This article describes in detail the preclinical science leading to the creation of the AE37 vaccine and examines use of this agent in multiple clinical trials for breast and prostate cancer. The safety profile of AE37 is discussed and opinions on the potential of the vaccine in breast and prostate cancer patient subsets along with other malignancies, are offered. Expert Opinion: Future trials utilizing the AE37 vaccine to treat other HER2-expressing malignancies are likely to see similar success, and this will be enhanced by combination immunotherapy. Ii-Key modification of other peptides of interest across oncology and v...
Source: Expert Opinion on Investigational Drugs - November 18, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Translesion Synthesis Inhibitors as a New Class of Cancer Chemotherapeutics.
Authors: Patel SM, Dash RC, Hadden MK Abstract Introduction: Translesion synthesis (TLS) is a DNA damage tolerance mechanism that replaces the replicative DNA polymerase with a specialized, low-fidelity TLS DNA polymerase that can copy past DNA lesions during active replication. Recent studies have demonstrated a primary role for TLS in replicating past DNA lesions induced by first-line genotoxic agents, resulting in decreased efficacy and acquired chemoresistance. With this in mind, targeting TLS as a combination strategy with first-line genotoxic agents has emerged as a promising approach to develop a new class o...
Source: Expert Opinion on Investigational Drugs - November 14, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

An overview on the use of antivirals for the treatment of patients with COVID19 disease.
Authors: Malinis M, McManus D, Davis M, Topal J Abstract Introduction: There is an urgent need for safe and efficacious antiviral drugs to improve outcomes for COVID-19 patients. Understanding SARS-CoV-2 virology can elucidate potential drug targets for the inhibition of viral replication. Areas Covered: This review offers insights into novel and repurposed drugs that may have activity against SARS-CoV-2. We searched the PubMed, Medline, Google Scholar, Web of Science and ClinicalTrials.gov for COVID-19 related therapy until September 15, 2020 using search words "SARS-CoV-2", "COVID-19", "a...
Source: Expert Opinion on Investigational Drugs - November 6, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Batten disease: an expert update on agents in preclinical and clinical trials.
Authors: Masten MC, Mink JW, Augustine EF PMID: 33135495 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - November 4, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Circadian rhythms in diabetic retinopathy: an overview of pathogenesis and investigational drugs.
This article offers an overview of the physiology of the biological clock and clock regulatory genes and presents an examination of the retinal clock. It discusses the pathogenic mechanisms of DR and emphasizes how circadian rhythm dysfunction at structural, physiological, metabolic and cellular levels, plays a critical role in the development of DR. The latter part of the paper sheds light on those investigational drugs (such as melatonin, tasimelteon and metformin) which exhibit potential in the treatment of DR by the targeting of circadian rhythm dysfunction. EXPERT OPINION: An enhanced understanding of circadian rh...
Source: Expert Opinion on Investigational Drugs - October 29, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Overview on the use of IL-6 agents in the treatment of patients with cytokine release syndrome (CRS) and pneumonitis related to COVID-19 disease.
Authors: Zhou Z, Price CC Abstract INTRODUCTION: A novel coronavirus pneumonia (COVID-19) has caused significant life loss and healthcare burden around the world. COVID-19 is known to cause a cytokine release syndrome (CRS) like response, and interleukin-6 (IL-6) is one of the cytokines involved. Clinicians are using IL-6 inhibitors to CRS, and researchers are investigating the use of IL-6 inhibitors, namely tocilizumab, sarilumab, siltuximab, in COVID-19 management. AREAS COVERED: In this article, we will discuss the pharmacology of these three inhibitors and summarize available clinical data via literature se...
Source: Expert Opinion on Investigational Drugs - October 25, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Lorecivivint, an intra-articular potential disease-modifying osteoarthritis drug.
Authors: Sabha M, Siaton BC, Hochberg MC Abstract INTRODUCTION: Osteoarthritis (OA) is the most common form of arthritis. Knee OA is associated with joint pain, activity limitation, physical disability, reduced health-related quality of life, and increased mortality. To date, all pharmacologic treatments for OA are directed towards pain management. However, Lorecivivint (LOR) is an investigational agent that has potential as a disease-modifying osteoarthritis drug (DMOAD). It modulates the Wnt signaling pathway by inhibiting CDC-like kinase 2 and dual-specificity tyrosine phosphorylation-regulated kinase 1 A which ...
Source: Expert Opinion on Investigational Drugs - October 25, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Aromatase inhibitors for the treatment of endometriosis: a systematic review about efficacy, safety and early clinical development.
Authors: Garzon S, Laganà AS, Barra F, Casarin J, Cromi A, Raffaelli R, Uccella S, Franchi M, Ghezzi F, Ferrero S Abstract INTRODUCTION: Pharmacotherapy has a key role in endometriosis treatment and management, however, a significant proportion of patients have only intermittent or limited benefits with current treatment options. Therefore, novel therapeutic approaches are necessary. AREAS COVERED: This systematic review provides an overview of the efficacy and safety of aromatase inhibitors (AIs) as monotherapies and combination therapies for endometriosis. A systematic literature search was performed f...
Source: Expert Opinion on Investigational Drugs - October 25, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Repurposing elesclomol, an investigational drug for the treatment of copper metabolism disorders.
Authors: Gohil VM PMID: 33081534 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - October 23, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Genetic prion disease: opportunities for early therapeutic intervention with rigorous pre-symptomatic trials.
Authors: Hermann P, Koch JC, Zerr I PMID: 33089731 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - October 23, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Clinical complexity of utilizing FGFR inhibitors in cancer therapeutics.
Authors: Chandana SR, Babiker HM, Mahadevan D Abstract INTRODUCTION: Fibroblast growth factor receptors (FGFR 1-4) are a highly conserved family of receptor tyrosine kinases, involved in several physiological processes. Genetic aberrations of FGFRs and their ligands, fibroblast growth factors (FGFs) are involved in several pathological processes including cancer. The FGF-FGFR axis has emerged as a treatment target in oncology. Because these aberrations drive cancer progression, the development of FGFR targeted therapies have been accelerated. Areas Covered: In this comprehensive review, we evaluate molecular pathol...
Source: Expert Opinion on Investigational Drugs - October 22, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

The nonalcoholic steatohepatitis (NASH) drug development graveyard: established hurdles and planning for future success.
Authors: Drenth JPH, Schattenberg JM Abstract Introduction Numerous pharmacological compounds that target the different molecular targets involved in the pathobiology of nonalcoholic steatohepatitis (NASH) are currently in clinical testing. So far, there are no regulatory approvals. Areas covered: This paper sheds light on the molecular pathways involved in NASH and the drugs targeting these pathways. We have identified 10 compounds whose clinical development program have been halted. Moreover, we explore early phase clinical trials and dissect the reasons for termination of development. Expert opinion: The main go...
Source: Expert Opinion on Investigational Drugs - October 22, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

A case study of foliglurax, the first clinical mGluR4 PAM for symptomatic treatment of Parkinson's disease: Translational gaps or a failing industry innovation model?
Authors: Bespalov A, Miller R, Pietraszek M, Kalinichev M, Doller D Abstract INTRODUCTION: Approximately 40% of Parkinson's disease (PD) patients that take mostly dopamine receptor agonists for motor fluctuations, experience the return of symptoms between regular doses. This is a phenomenon known as "OFF periods". Positive allosteric modulators (PAMs) of metabotropic glutamate receptor 4 (mGluR4) are a promising non-dopaminergic mechanism with potential to address the unmet need of patients suffering from OFF periods. Foliglurax is the first mGluR4 PAM that has advanced into clinical testing in PD patient...
Source: Expert Opinion on Investigational Drugs - October 22, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Futibatinib, an investigational agent for the treatment of intrahepatic cholangiocarcinoma: evidence to date and future perspectives.
Authors: Rizzo A, Ricci AD, Brandi G Abstract INTRODUCTION: Biliary tract cancers (BTCs) are poor prognosis malignancies usually classified in intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer. In the last few years, novel treatment targets have been identified in iCCA patients, including fibroblast growth factor receptor (FGFR) aberrations; thus, several FGFR inhibitors are currently being developed, some of which have already suggested interesting efficacy and adequate safety in phase I and phase II trials regarding refractory iCCA. AREAS ...
Source: Expert Opinion on Investigational Drugs - October 20, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Dr Sandi Dunn illuminates emerging key treatment approaches and companion diagnostics for triple negative breast cancer.
Authors: Dunn S PMID: 33070643 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - October 20, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Emerging and investigational targeted chemotherapy and immunotherapy agents for metastatic brain tumors.
This study reviews novel drug regimens that are under investigation in phase 1 and 2 clinical trials. To identify relevant therapies under clinical investigation, a search was performed on http://clinicaltrials.gov and Pubmed with the key words brain metastasis, Phase I clinical trial, and Phase II clinical trial from 2016 to 2020. The authors detail the mechanisms of action of all trial agents, outline evidence for their utility, and summarize the current state of the field. Expert opinion: Current advancements in the medical management of brain metastases can be categorized into targeted therapies, methods of overcoming ...
Source: Expert Opinion on Investigational Drugs - October 14, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Tislelizumab: An investigational anti-PD-1 antibody for the treatment of advanced non-small cell lung cancer (NSCLC).
Authors: Liu SY, Wu YL Abstract INTRODUCTION: Non-small cell lung cancer (NSCLC) accounts for most lung cancers worldwide and has a poor prognosis at later stages; programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have provided promising new treatment approaches for these patients. Tislelizumab, an anti-PD-1 monoclonal antibody, was engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Tislelizumab has demonstrated clinical activity and is approved i...
Source: Expert Opinion on Investigational Drugs - October 14, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

A Randomized, Double-blind, Parallel Pharmacokinetic Study Comparing the Trastuzumab Biosimilar Candidate, AryoTrust ®, and Reference Trastuzumab in Healthy Subjects.
CONCLUSION: AryoTrust® was well tolerated, had a similar safety profile to reference trastuzumab, and its pharmacokinetic bioequivalence was confirmed. Trial Registration The trial is registered at Indian Trials Registry (CTRI/2019/03/018218). PMID: 33016783 [PubMed - as supplied by publisher] (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - October 7, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

ELX-02: an investigational read-through agent for the treatment of nonsense mutation related genetic disease.
Authors: Kerem E Abstract INTRODUCTION: ELX-02, an investigational compound that is structurally an aminoglycoside analogue, induces read-through of nonsense mutations through interaction with the ribosome, through which full-length functional proteins can be produced. It is being developed as a therapy for genetic diseases caused by nonsense mutations such as cystic fibrosis (CF) and nephropathic cystinosis. In Phase 1 clinical trials, 105 volunteers were exposed to ELX-02. To date, ELX-02 is well tolerated and there has been no reported treatment-related serious adverse events or deaths. Areas Covered: The develo...
Source: Expert Opinion on Investigational Drugs - September 27, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

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