Expert Opinion on Emerging Drugs最新文献

{"title":"Emerging drugs for the treatment of major depressive disorder.","authors":"Jennifer Hong,&nbsp;Darian Vernon,&nbsp;Jelena Kunovac,&nbsp;Stephen Stahl","doi":"10.1080/14728214.2022.2117297","DOIUrl":"https://doi.org/10.1080/14728214.2022.2117297","url":null,"abstract":"<p><strong>Introduction: </strong>Major depressive disorder (MDD) continues to be one of the highest contributors to disease burden and years lived with disability in the world. Current existing treatments have been associated with intolerable side effects, long onset of action and suboptimal remission rates. Newer agents are being developed that will be reviewed here, such as glutamate and gamma-aminobutyric acid (GABA) and the reinvigorated testing of psychedelic drugs. This review will summarize the target mechanisms of the newer ADTs currently in development and available on the market.</p><p><strong>Areas covered: </strong>It briefly covers the existing agents for MDD and treatment-resistant depression (TRD) and the need for new agents with higher efficacy. Therapeutic agents currently in Phase II or later clinical trials are listed and discussed, based on a thorough review of the US National Institutes of Health clinicaltrials.gov index and a search of the Informa Pharmaprojects database. Compounds of interest are grouped into scientific rationale and include atypical antipsychotics, GABA positive allosteric modulators, glutamatergic agents, opioids, orexin 2 receptor antagonists, and psychedelics.</p><p><strong>Expert opinion: </strong>New therapeutic agents currently in development are promising, with a more rapid onset of action and the ability to augment and treat TRD.</p>","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":"27 3","pages":"263-275"},"PeriodicalIF":3.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10491766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging drugs for the treatment of bladder storage dysfunction.","authors":"Karl-Erik Andersson","doi":"10.1080/14728214.2022.2113057","DOIUrl":"https://doi.org/10.1080/14728214.2022.2113057","url":null,"abstract":"<p><strong>Introduction: </strong>Current drug treatment of lower urinary tract disorders, for example, overactive bladder syndrome and lower urinary tract symptoms associated with benign prostatic hyperplasia, is moderately effective, has a low treatment persistence and some short- and long-term adverse events. Even if combination therapy with approved drugs may offer advantages in some patients, there is still a need for new agents.</p><p><strong>Areas covered: </strong>New b₃-adrenoceptor agonists, antimuscarinics, the naked Maxi-K channel gene, a novel 5HT/NA reuptake inhibitor and soluble guanylate cyclase activators are discussed. Focus is given to P2X3 receptor antagonists, small molecule blockers of TRP channels, the roles of cannabis on incontinence in patients with multiple sclerosis, and of drugs acting directly on CB1 and CB2 receptor or indirectly via endocannabinoids by inhibition of fatty acid aminohydrolase.</p><p><strong>Expert opinion: </strong>New potential alternatives to currently used drugs/drug principles are emerging, but further clinical testing is required before they can be evaluated as therapeutic alternatives. It seems that for the near future individualized treatment with approved drugs and their combinations will be the prevailing therapeutic approach.</p>","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":"27 3","pages":"277-287"},"PeriodicalIF":3.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10842229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging immune checkpoint inhibitors for the treatment of non-small cell lung cancer.","authors":"Helena Bote,&nbsp;Andrés Mesas,&nbsp;Javier Baena,&nbsp;Mercedes Herrera,&nbsp;Luis Paz-Ares","doi":"10.1080/14728214.2022.2113377","DOIUrl":"https://doi.org/10.1080/14728214.2022.2113377","url":null,"abstract":"<p><strong>Introduction: </strong>Over the last decade, immune checkpoint inhibitors (ICIs) have impacted on the standard therapy for patients with non-small cell lung cancer (NSCLC). ICIs first showed efficacy in patients with advanced disease who had progressed after chemotherapy, later reaching the first-line therapy context alone, in combination with chemotherapy, and/or with dual-immunotherapy regimens.</p><p><strong>Areas covered: </strong>Most of their benefit is, however, restricted to just 20% of patients due to primary or emergence of acquired resistance. In this review, we will describe the role of new emerging ICIs in the current panorama of NSCLC therapeutic approaches, not only in metastatic disease but also in locally advanced stage disease, with specific focus on those drugs under investigation in Phase 2/3 clinical trials.</p><p><strong>Expert opinion: </strong>Several new ICIs are now under investigation to optimize NSCLC patient management; these are usually used in combination with other well-known agents, such as 'traditional' ICIs and chemotherapy, or with other newly developed drugs. Identification of better biomarkers will provide personalized treatment approaches to overcome patient-specific immune resistance.</p>","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":"27 3","pages":"289-300"},"PeriodicalIF":3.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10496972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging tyrosine kinase inhibitors for head and neck cancer.","authors":"Zhen Long,&nbsp;Jennifer R Grandis,&nbsp;Daniel E Johnson","doi":"10.1080/14728214.2022.2125954","DOIUrl":"10.1080/14728214.2022.2125954","url":null,"abstract":"<p><strong>Introduction: </strong>Conventional regimens for head and neck squamous cell carcinoma (HNSCC) are limited in efficacy and are associated with adverse toxicities. Food and Drug Administration (FDA) approved molecular targeting agents include the HER1 (EGFR)-directed monoclonal antibody cetuximab and the immune checkpoint inhibitors nivolumab and pembrolizumab. However, clinical benefit is only seen in roughly 15-20% of HNSCC patients treated with these agents. New molecular targeting agents are needed that either act with monotherapeutic activity against HNSCC tumors or enhance the activities of current therapies, particularly immunotherapy. Small-molecule tyrosine kinase inhibitors (TKIs) represent a viable option toward this goal.</p><p><strong>Areas covered: </strong>This review provides an update on TKIs currently under investigation in HNSCC. We focus our review on data obtained and trials underway in HNSCC, including salivary gland cancers and nasopharyngeal carcinomas, but excluding thyroid cancer and esophageal cancer.</p><p><strong>Expert opinion: </strong>While some emerging TKIs have shown clinical benefit, the positive effects have, largely, been modest. The design of clinical trials of TKIs has been hampered by a lack of understanding of biomarkers that can be used to define patient populations most likely to respond. Further preclinical and translational studies to define biomarkers of TKI response will be critically important.</p>","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":"27 3","pages":"333-344"},"PeriodicalIF":3.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9987561/pdf/nihms-1857632.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9390129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging medicines to improve the basic defect in cystic fibrosis.","authors":"Isabelle Fajac,&nbsp;Isabelle Sermet-Gaudelus","doi":"10.1080/14728214.2022.2092612","DOIUrl":"https://doi.org/10.1080/14728214.2022.2092612","url":null,"abstract":"<p><strong>Introduction: </strong>Cystic fibrosis (CF) is a severe autosomal recessive disorder featuring exocrine pancreatic insufficiency and bronchiectasis. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (<i>CFTR</i>) encoding the CFTR protein, which is an anion channel. CF treatment has long been based only on intensive symptomatic treatment. During the last 10 years, new drugs called CFTR modulators aiming at restoring the CFTR protein function have become available, and they will benefit around 80% of patients with CF. However, more than 10% of <i>CFTR</i> mutations do not produce any CFTR protein for CFTR modulators to act upon.</p><p><strong>Areas covered: </strong>The development of CFTR modulators and their effectiveness in patients with CF will be reviewed. Then, the different strategies to treat patients bearing mutations non-responsive to CFTR modulators will be covered. They comprise DNA- and RNA-based therapies, readthrough agents for nonsense mutations, and cell-based therapies.</p><p><strong>Expert opinion: </strong>CF disease has changed tremendously since the advent of CFTR modulators. For mutations that are not amenable to CFTR modulators, new approaches that are being developed benefit from advances in molecular therapy, but many challenges will have to be solved before they can be safely translated to patients.</p>","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":"27 3","pages":"229-239"},"PeriodicalIF":3.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10491284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging kinase inhibitors for the treatment of pancreatic ductal adenocarcinoma.","authors":"Udo Rudloff","doi":"10.1080/14728214.2022.2134346","DOIUrl":"10.1080/14728214.2022.2134346","url":null,"abstract":"<p><strong>Introduction: </strong>Pancreatic cancer is one of the deadliest solid organ cancers. In the absence of specific warning symptoms pancreatic cancer is diagnosed notoriously late. Current systemic chemotherapy regimens extend survival by a mere few months. With the advances in genetic, proteomic, and immunological profiling there is strong rationale to test kinase inhibitors to improve outcome.</p><p><strong>Areas covered: </strong>This review article provides a comprehensive summary of approved treatments and past, present, and future developments of kinase inhibitors in pancreatic cancer. Emerging roles of protein kinase inhibitors are discussed in the context of the unique stroma, the lack of high-prevalence therapeutic targets and rapid emergence of acquired resistance, novel immuno-oncology kinase targets, and recent medicinal chemistry advances.</p><p><strong>Expert opinion: </strong>Due to the to-date frequent failure of protein kinase inhibitors indiscriminately administered to unselected pancreatic cancer patients, there is a shift toward the development of these agents in molecularly defined subgroups which are more likely to respond. The development of accurate biomarkers to select patients who are the best candidates based on a detailed understanding of mechanism of action, pro-survival roles, and mediation of resistance of targeted kinases will be critical for the future development of protein kinase inhibitors in this disease.</p>","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":"27 3","pages":"345-368"},"PeriodicalIF":2.7,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9793333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10492270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging injectable therapies for osteoarthritis.","authors":"Julia Sewell,&nbsp;Andrew Östör","doi":"10.1080/14728214.2022.2125506","DOIUrl":"https://doi.org/10.1080/14728214.2022.2125506","url":null,"abstract":"<p><p>Osteoarthritis (OA) affects more than 240 million people worldwide. In 2016, the Osteoarthritis Research Society International submitted a report to the United States Food and Drug Administration highlighting OA as a 'serious' disease, and appealed for the urgent development and review of new therapies to address a significant unmet need. Despite this, international guidelines for the treatment of OA have been largely unchanged for over a decade. There is now an updated understanding that OA is more than simply a non-inflammatory 'wear-and-tear' process involving articular cartilage. Based on this, potential emerging therapies are being developed that target novel inflammatory, pain, and regeneration pathways. Drugs targeting the latter are being lauded as 'Disease-Modifying Osteoarthritis Drugs' - a concept which has so far proved elusive in OA research. While this review does not recommend a change in current practice, it should prompt readers to rethink the OA treatment paradigm. The global pandemic has added another layer of consideration when managing patients with OA. At a time when there is more strain on hospital systems, there is a need to expand our pharmacological armamentarium in order to manage OA without elective surgery and hospital admission.</p>","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":"27 3","pages":"311-320"},"PeriodicalIF":3.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10483513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is clinical trial data showing positive progress for the treatment of eosinophilic esophagitis?","authors":"Robert D Pesek,&nbsp;Sandeep K Gupta","doi":"10.1080/14728214.2022.2136164","DOIUrl":"https://doi.org/10.1080/14728214.2022.2136164","url":null,"abstract":"Eosinophilic gastrointestinal disorders (EGIDs) are characterized by GI tract dysfunction (dysphagia, vomiting, gastro-esophageal reflux, abdominal pain, diarrhea, etc.) and findings of increased tissue eosinophils on biopsy. These disorders can affect any segment of the GI tract, and the best characterized is eosinophilic esophagitis (EoE). Originally described as a distinct entity in the 1990s, EoE is now recognized worldwide with defined clinical, endoscopic, and histologic diagnostic criteria as well as widely accepted guidelines for management [1]. Treatment options include food elimination diets, which focus on removal of the triggering food(s), or use of medications, to induce disease remission. There are generally three categories of medications utilized: proton-pump inhibitors (PPIs), swallowed, topical corticosteroids (TCS), and biologics. In EoE, PPIs function as anti-inflammatory agents by decreasing the expression of Th2 (allergic) cytokines and improving the disrupted barrier function of the esophagus. Swallowed, topical corticosteroids and many biologics function in a similar way: downregulation of Th2 cytokines, repair of esophageal barrier function, and prevention of tissue remodeling. In trials of PPIs, between 20% and 50% of patients demonstrate clinical and histologic improvement with high-dose monotherapy and the majority maintain this with long-term use [2]. PPIs are positioned among the first-line treatments for EoE, although they are not approved by the FDA in the United States for this indication. TCS have undergone the most extensive evaluation of any therapeutic for EoE. There are currently two formulations utilized in the United States: budesonide, which is mixed into a ‘slurry,’ and fluticasone propionate, which is administered as an aerosol through an MDI device. Both formulations are swallowed, providing a topical effect in the esophagus and each is effective for both induction of clinical and histological remission of EoE as well as long-term maintenance therapy [3]. Biologics have garnered much recent attention, likely due to their success in a variety of other disorders including atopic diseases such as asthma and atopic dermatitis. Based upon this discussion, it would seem clear that there are multiple, effective therapies for EoE; however, until recently none have been approved by the FDA for use in the United States. The reasoning behind this, at least in part, can likely trace back to how EoE is diagnosed and the challenges faced in therapeutic trials for this disease. EoE is a clinicopathologic diagnosis requiring both clinical symptoms of gastrointestinal dysfunction and histologic findings of increased eosinophils/eosinophil activity in the affected tissue [4]. Treatment outcomes have focused on reducing tissue eosinophil load and improving the clinical symptoms and endoscopic features [5]. In early clinical trials, the results were often hampered by a lack of standardized outcome measures [6–8]. In additi","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":"27 3","pages":"225-227"},"PeriodicalIF":3.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10496982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging drugs for the treatment of glaucoma: a review of phase II & III trials.","authors":"Tyler M Kaplan,&nbsp;Arthur J Sit","doi":"10.1080/14728214.2022.2110240","DOIUrl":"https://doi.org/10.1080/14728214.2022.2110240","url":null,"abstract":"<p><strong>Introduction: </strong>Glaucoma is a progressive optic neuropathy and the leading cause of irreversible vision loss. By 2040, the number of individuals with glaucoma is expected to nearly double. The only known modifiable risk factor for glaucoma is intraocular pressure. Topical medications are often used as first-line therapies. Although there are numerous available treatments, there continues to be a need for the development of new medical therapies due to variable response, intolerable side-effect profiles in some patients, and elevated intraocular pressure refractory to other treatments.</p><p><strong>Areas covered: </strong>This review will cover glaucoma medications currently undergoing phase II and III of drug development.</p><p><strong>Expert opinion: </strong>There are numerous drugs currently in development that have demonstrated significant and clinically relevant reduction of intraocular pressure. Differentiating factors include improved tolerability, novel mechanisms of action, multiple mechanisms of action, or superior IOP reduction. However, the availability of generic prostaglandin analogs may limit adoption of these novel compounds as first-line agents, except for certain subgroups of glaucoma patients. Use as adjuvant or second-line therapy appears more likely for the majority of glaucoma patients.</p>","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":"27 3","pages":"321-331"},"PeriodicalIF":3.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10858542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidermal growth factor receptor-targeted therapy for the treatment of non-small cell lung cancer: a review of phase II and III trials","authors":"Hong-Lian Lu, G. Jie, Yi‐Long Wu","doi":"10.1080/14728214.2022.2063836","DOIUrl":"https://doi.org/10.1080/14728214.2022.2063836","url":null,"abstract":"ABSTRACT Introduction Epidermal growth factor receptor (EGFR) is one of the most common driver gene mutations in non-small-cell lung cancer (NSCLC). EGFR-tyrosine kinase inhibitors (TKIs) monotherapy and EGFR-TKI combined with chemotherapy or anti-angiogenesis drugs have significantly prolonged the survival of patients with EGFR-mutant NSCLC. However, disease progression caused by acquired resistance to EGFR-TKIs is inevitable. And patients with EGFR exon 20ins showed limited efficacy to EGFR-TKIs. Areas covered In this review, we initially evaluated the efficacy of existing treatments for EGFR-mutant NSCLC. Second, we reviewed the ongoing phase II and III clinical trials, provided the latest results, discussed the scientific rationale of these trials and the potential development issues. Expert opinion The application of EGFR-TKIs has greatly changed the therapeutic strategies for advanced and resected NSCLC with EGFR mutations, and the 5-year overall survival (OS) rate for advanced NSCLC was close to 40%. The current research direction for the treatment of patients with EGFR mutations focuses on the following three aspects: uncommon EGFR mutation subtypes, brain metastases, and EGFR TKI-based combination therapy. Future studies on EGFR-mutant NSCLC therapy will focus on overcoming EGFR-TKI-related resistance, preventing drug resistance in advance, and developing bispecific antibody drugs.","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":"27 1","pages":"111 - 126"},"PeriodicalIF":3.4,"publicationDate":"2022-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47773104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}