REGN-EB3: First Approval
This article summarizes the milestones in the development of REGN-EB3 leading to this first approval for the treatment of infection caused byZaire ebolavirus (Ebola virus) in adult and paediatric patients. (Source: Drugs)
Source: Drugs - January 11, 2021 Category: Drugs & Pharmacology Source Type: research

Lumasiran: First Approval
This article summarizes the milestones in the development of lumasiran leading to this first approval. (Source: Drugs)
Source: Drugs - January 6, 2021 Category: Drugs & Pharmacology Source Type: research

Vedolizumab and Extraintestinal Manifestations in Inflammatory Bowel Disease
AbstractIn Crohn ’s disease and ulcerative colitis, inflammation is not limited to the digestive tract. Extraintestinal manifestations (EIMs), which affect up to 50% of patients, can substantially impair quality of life. EIMs may parallel luminal disease activity or have an independent course. They most commonly i nvolve the musculoskeletal system (e.g., peripheral or axial arthritis) and skin (e.g., erythema nodosum and pyoderma gangrenosum). Less commonly, the hepatobiliary tract (e.g., primary sclerosing cholangitis [PSC]) and the eye (e.g., episcleritis, scleritis, and uveitis) are involved. Although the pathophy...
Source: Drugs - January 5, 2021 Category: Drugs & Pharmacology Source Type: research

Strategies Targeting the Innate Immune Response for the Treatment of Hepatitis C Virus-Associated Liver Fibrosis
AbstractDirect-acting antivirals eliminate hepatitis C virus (HCV) in more than 95% of treated individuals and may abolish liver injury, arrest fibrogenesis, and reverse fibrosis and cirrhosis. However, liver regeneration is usually a slow process that is less effective in the late stages of fibrosis. What is more, fibrogenesis may prevail in patients with advanced cirrhosis, where it can progress to liver failure and hepatocellular carcinoma. Therefore, the development of antifibrotic drugs that halt and reverse fibrosis progression is urgently needed. Fibrosis occurs due to the repair process of damaged hepatic tissue, w...
Source: Drugs - January 5, 2021 Category: Drugs & Pharmacology Source Type: research

Are New Antiretroviral Treatments Increasing the Risk of Weight Gain?
AbstractThere is a growing body of evidence from both observational and randomised trials implicating integrase inhibitors, particularly dolutegravir and bictegravir, with the development of weight gain and obesity in people living with HIV. Evidence with cabotegravir, the newest integrase inhibitor, is limited. Reasons for weight gain are currently unknown. Proposed mechanisms include improved tolerability, direct impact on adipogenesis, and gut microbiome disturbance. Clinical trials have found that weight gain with integrase inhibitors is greatest for women and people of Black ethnicity. Evidence suggests that the nucle...
Source: Drugs - January 5, 2021 Category: Drugs & Pharmacology Source Type: research

Detecting and Targeting NTRK Fusions in Cancer in the Era of Tumor Agnostic Oncology
AbstractGene rearrangements involving the neurotrophic receptor kinase genesNTRK1,NTRK2, andNTRK3 (referred to as TRK, encoding TRKA, TRKB, and TRKC, respectively) result in highly oncogenic fusions. TRK fusions are rare, with a prevalence of
Source: Drugs - January 5, 2021 Category: Drugs & Pharmacology Source Type: research

Managing Diabetic Foot Ulcers: Pharmacotherapy for Wound Healing
This article highlights those trials, and describes the current pharmacological management of the diabetic foot ulcer and the advances that have been made in wound therapy to date. It provides an overview of topical and systemic pharmacotherapies in current use and those in development for future use in managing the diabetic foot. For each treatment, proposed mechanisms of action and evidence available to support their clinical use are presented. There is supporting randomised, controlled evidence for sucrose octasulfate in the treatment of neuro-ischaemic ulcers, and multi-layered patch of autologous leucocytes, platelets...
Source: Drugs - December 31, 2020 Category: Drugs & Pharmacology Source Type: research

Evolving Role of Immunotherapy in Metastatic Castration Refractory Prostate Cancer
We describe the result s of clinical trials of immune checkpoint inhibitors in patients with metastatic castration-resistant prostate cancer; either as single agents or in combination with other checkpoint inhibitors, poly (ADP-ribose) polymerase (PARP) inhibitors, tyrosine kinase inhibitors, novel hormonal therapies, che motherapies, and radioligands. Finally, we review upcoming immunotherapies, including novel monoclonal antibodies, chimeric-antigen receptor (CAR) T cells, Bi-Specific T cell Engagers (BiTEs), therapies targeting the adenosine pathway, and other miscellaneous agents. (Source: Drugs)
Source: Drugs - December 28, 2020 Category: Drugs & Pharmacology Source Type: research

Inhibiting CDK4/6 in Breast Cancer with Palbociclib, Ribociclib, and Abemaciclib: Similarities and Differences
AbstractThe cyclin-dependent kinase (CDK) 4/6 inhibitors belong to a new class of drugs that interrupt proliferation of malignant cells by inhibiting progression through the cell cycle. Three such inhibitors, palbociclib, ribociclib, and abemaciclib were recently approved for breast cancer treatment in various settings and combination regimens. On the basis of their impressive efficacy, all three CDK4/6 inhibitors now play an important role in the treatment of patients with HR+, HER2 − breast cancer; however, their optimal use still needs to be established. The three drugs have many similarities in both pharmacokinet...
Source: Drugs - December 28, 2020 Category: Drugs & Pharmacology Source Type: research

Correction to: Decitabine/Cedazuridine: First Approval
The article Decitabine/Cedazuridine: First Approval, written by Sohita Dhillon, was originally published electronically in SpringerLink on 29 August 2020 without open access. (Source: Drugs)
Source: Drugs - December 28, 2020 Category: Drugs & Pharmacology Source Type: research

Alemtuzumab: A Review in Relapsing Remitting Multiple Sclerosis
AbstractAlemtuzumab (Lemtrada®) is an anti-CD52 monoclonal antibody approved in the EU for the treatment of highly active relapsing-remitting multiple sclerosis (RRMS). In phase 3 trials in patients with active RRMS, intravenous alemtuzumab was more effective than subcutaneous interferon β-1a in terms of decreasing relapse rates (in treatment-naïve or -experienced patients) and disability progression (treatment-experienced patients). Treatment benefits were maintained over up to 9 years of follow-up, with ≈ 50% of patients not requiring retreatment. The efficacy of alemtuzumab in patients with highly ...
Source: Drugs - December 24, 2020 Category: Drugs & Pharmacology Source Type: research

50 Years of Drugs
(Source: Drugs)
Source: Drugs - December 24, 2020 Category: Drugs & Pharmacology Source Type: research

Updated Overall Survival in a Randomized Study Comparing Dacomitinib with Gefitinib as First-Line Treatment in Patients with Advanced Non-Small-Cell Lung Cancer and EGFR -Activating Mutations
ConclusionsThe OS benefit from first-line treatment with dacomitinib versus gefitinib was maintained after extended follow-up in patients with advanced NSCLC withEGFR-activating mutations.ClinicalTrials.govNCT01774721 (registered 24 January 2013). (Source: Drugs)
Source: Drugs - December 17, 2020 Category: Drugs & Pharmacology Source Type: research

Correction to: Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma
Correction in reviewer name. (Source: Drugs)
Source: Drugs - December 17, 2020 Category: Drugs & Pharmacology Source Type: research

Enarodustat: First Approval
This article summarizes the milestones in the development of enarodustat leading to this first approval for anaemia associated with CKD. (Source: Drugs)
Source: Drugs - December 15, 2020 Category: Drugs & Pharmacology Source Type: research

50 Years On Still Relevant
(Source: Drugs)
Source: Drugs - December 12, 2020 Category: Drugs & Pharmacology Source Type: research

Correction to: Selpercatinib: First Approval
The original article can be found online. (Source: Drugs)
Source: Drugs - December 11, 2020 Category: Drugs & Pharmacology Source Type: research

Sphingosine 1-phosphate Receptor Modulator Therapy for Multiple Sclerosis: Differential Downstream Receptor Signalling and Clinical Profile Effects
AbstractLysophospholipids are a class of bioactive lipid molecules that produce their effects through various G protein-coupled receptors (GPCRs). Sphingosine 1-phosphate (S1P) is perhaps the most studied lysophospholipid and has a role in a wide range of physiological and pathophysiological events, via signalling through five distinct GPCR subtypes, S1PR1 to S1PR5. Previous and continuing investigation of the S1P pathway has led to the approval of three S1PR modulators, fingolimod, siponimod and ozanimod, as medicines for patients with multiple sclerosis (MS), as well as the identification of new S1PR modulators currently...
Source: Drugs - December 8, 2020 Category: Drugs & Pharmacology Source Type: research

The Development of Cladribine Tablets for the Treatment of Multiple Sclerosis: A Comprehensive Review
AbstractCladribine is a purine nucleoside analog initially developed in the 1970s as a treatment for various blood cancers. Due to the molecule ’s ability to preferentially reduce T and B lymphocytes, it has been developed into an oral formulation for the treatment of multiple sclerosis (MS). The unique proposed mechanism of action of cladribine allows for the therapy to be delivered orally over two treatment-week cycles per year, one cyc le at the beginning of the first month and one cycle at the beginning of the second month of years 1 and 2, with the potential for no further cladribine treatment required in years ...
Source: Drugs - November 28, 2020 Category: Drugs & Pharmacology Source Type: research

Imeglimin: Current Development and Future Potential in Type 2 Diabetes
AbstractImeglimin is the first of the “glimins,” a new class of drugs developed for the treatment of type 2 diabetes mellitus (T2DM). This review highlights its mechanism of action and its context in the field of T2DM treatment. Preclinical data in multiple rodent models have detailed significant effects on mitochondria, particularl y improved mitochondrial bioenergetics. This includes changes favoring complex II and complex III metabolism, a mechanism potentially promoting increased fatty acid oxidation, leading to the decrease in hepatic lipid accumulation observed in these mice. Imeglimin was also shown to i...
Source: Drugs - November 28, 2020 Category: Drugs & Pharmacology Source Type: research

Lefamulin: A Novel Oral and Intravenous Pleuromutilin for the Treatment of Community-Acquired Bacterial Pneumonia
AbstractLefamulin is a novel oral and intravenous (IV) pleuromutilin developed as a twice-daily treatment for community-acquired bacterial pneumonia (CABP). It is a semi-synthetic pleuromutilin with a chemical structure that contains a tricyclic core of five-, six-, and eight-membered rings and a 2-(4-amino-2-hydroxycyclohexyl)sulfanylacetate side chain extending from C14 of the tricyclic core. Lefamulin inhibits bacterial protein synthesis by binding to the 50S bacterial ribosomal subunit in the peptidyl transferase center (PTC). The pleuromutilin tricyclic core binds to a pocket close to the A site, while the C14 side ch...
Source: Drugs - November 28, 2020 Category: Drugs & Pharmacology Source Type: research

Neuronal Ceroid Lipofuscinosis: Potential for Targeted Therapy
AbstractNeuronal ceroid lipofuscinosis (NCLs) is a group of inherited neurodegenerative lysosomal storage diseases that together represent the most common cause of dementia in children. Phenotypically, patients have visual impairment, cognitive and motor decline, epilepsy, and premature death. A primary challenge is to halt and/or reverse these diseases, towards which developments in potential effective therapies are encouraging. Many treatments, including enzyme replacement therapy (for CLN1 and CLN2 diseases), stem-cell therapy (for CLN1, CLN2, and CLN8 diseases), gene therapy vector (for CLN1, CLN2, CLN3, CLN5, CLN6, CL...
Source: Drugs - November 26, 2020 Category: Drugs & Pharmacology Source Type: research

Filgotinib: First Approval
This article summarizes the milestones in the development of filgotinib leading to this first approval. (Source: Drugs)
Source: Drugs - November 25, 2020 Category: Drugs & Pharmacology Source Type: research

Sofpironium Bromide: First Approval
This article summarizes the milestones in the development of sofpironium bromide gel leading to this first approval for the treatment of PAH. (Source: Drugs)
Source: Drugs - November 24, 2020 Category: Drugs & Pharmacology Source Type: research

Treatment Sequencing for Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer
AbstractNon-small-cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases and is the leading cause of cancer-related deaths. Most NSCLC patients are diagnosed with advanced disease and require systemic treatment. Despite emerging advances in chemotherapy and immunotherapy, the prognosis of stage IV patients remains poor. However, the discovery of oncogenic driver mutations including mutations in the epidermal growth factor receptor (EGFR), the anaplastic lymphoma kinase (ALK) and others, characterize a subset of patients with the opportunity of targeted therapies. Fusions between the ALK and echinoderm mic...
Source: Drugs - November 23, 2020 Category: Drugs & Pharmacology Source Type: research

Acknowledgement to Referees
(Source: Drugs)
Source: Drugs - November 23, 2020 Category: Drugs & Pharmacology Source Type: research

Abuse and Misuse of Pregabalin and Gabapentin: A Systematic Review Update
ConclusionEvidence suggests that gabapentinoid misuse/abuse represents a growing trend that is causing significant patient harm. Prescribers should exercise appropriate caution with use in high-risk populations and monitor for signs of misuse or abuse. (Source: Drugs)
Source: Drugs - November 19, 2020 Category: Drugs & Pharmacology Source Type: research

Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia
In conclusion, fixed-duration venetoclax + obinutuzumab represents an important chemotherapy-free first-line treatment option for patients with CLL, particularly those who are not fit enough to receive intensive chemoimmunotherapy. (Source: Drugs)
Source: Drugs - November 17, 2020 Category: Drugs & Pharmacology Source Type: research

Correction to: Trastuzumab Emtansine: A Review of Its Adjuvant Use in Residual Invasive HER2-Positive Early Breast Cancer
The author has alerted us to the following error. (Source: Drugs)
Source: Drugs - November 13, 2020 Category: Drugs & Pharmacology Source Type: research

TRPV1-Targeted Drugs in Development for Human Pain Conditions
AbstractThe transient receptor potential vanilloid-1 (TRPV1) is a non-specific cation channel known for its sensitivity to pungent vanilloid compound (i.e. capsaicin) and noxious stimuli, including heat, low pH or inflammatory mediators. TRPV1 is found in the somatosensory system, particularly primary afferent neurons that respond to damaging or potentially damaging stimuli (nociceptors). Stimulation of TRPV1 evokes a burning sensation, reflecting a central role of the channel in pain. Pharmacological and genetic studies have validated TRPV1 as a therapeutic target in several preclinical models of chronic pain, including c...
Source: Drugs - November 9, 2020 Category: Drugs & Pharmacology Source Type: research

Therapeutic Options in Hereditary Optic Neuropathies
AbstractOptions for the effective treatment of hereditary optic neuropathies have been a long time coming. The successful launch of the antioxidant idebenone for Leber ’s Hereditary Optic Neuropathy (LHON), followed by its introduction into clinical practice across Europe, was an important step forward. Nevertheless, other options, especially for a variety of mitochondrial optic neuropathies such as dominant optic atrophy (DOA), are needed, and a number of pharm aceutical agents, acting on different molecular pathways, are currently under development. These include gene therapy, which has reached Phase III developmen...
Source: Drugs - November 7, 2020 Category: Drugs & Pharmacology Source Type: research

Correction to: Ripretinib: First Approval
The original article can be found online. (Source: Drugs)
Source: Drugs - November 6, 2020 Category: Drugs & Pharmacology Source Type: research

Pharmacotherapy for Hospitalized Patients with COVID-19: Treatment Patterns by Disease Severity
ConclusionsCareful consideration of disease severity and other determinants of COVID-19 drug use is necessary for appropriate conduct and interpretation of non-randomized studies evaluating outcomes of COVID-19 treatments. (Source: Drugs)
Source: Drugs - November 5, 2020 Category: Drugs & Pharmacology Source Type: research

Pralsetinib: First Approval
This article summarizes the milestones in the development of pralsetinib leading to this first approval. (Source: Drugs)
Source: Drugs - November 2, 2020 Category: Drugs & Pharmacology Source Type: research

Correction to: Triheptanoin: First Approval
The article Triheptanoin: First Approval, written by Matt Shirley, was originally published electronically in SpringerLink on 8 September 2020 without open access. After publication in volume 80, issue 15, pages 1595 –1600 Ultragenyx Pharmaceutical Inc., requested that the article be Open Choice to make the article an open access publication. (Source: Drugs)
Source: Drugs - October 22, 2020 Category: Drugs & Pharmacology Source Type: research

Symptomatic Efficacy of Pharmacological Treatments for Knee Osteoarthritis: A Systematic Review and a Network Meta-Analysis with a 6-Month Time Horizon
ConclusionSix months of treatment with IA HA, pCGS, pCS, vitamin D and the combination of IA HA and triamcinolone improve pain and/or physical function in patients suffering from knee OA. (Source: Drugs)
Source: Drugs - October 19, 2020 Category: Drugs & Pharmacology Source Type: research

Correction to: Oliceridine: First Approval
The original article can be found online. (Source: Drugs)
Source: Drugs - October 19, 2020 Category: Drugs & Pharmacology Source Type: research

Immune Therapy, or Antiviral Therapy, or Both for COVID-19: A Systematic Review
ConclusionsBeyond the supportive therapy, up to now the best therapeutic approach for COVID-19 may be a three-step combination therapy, including remdesivir 100  mg/day (200 mg loading dose on first day) in the first stage of the disease, and combined dexamethasone 6 mg/day plus baricitinib 4 mg/day to target the immune dysregulation triggered by the SARS-CoV-2 infection. The promising results of anakinra should be confirmed by the ongoing RCTs. (Source: Drugs)
Source: Drugs - October 17, 2020 Category: Drugs & Pharmacology Source Type: research

Imlifidase: First Approval
This article summarizes the milestones in the development of imlifidase leading to this first approval for desensitization treatment of highly sensitized adult kidney transplant patients with positive crossmatch against an available deceased d onor. (Source: Drugs)
Source: Drugs - October 15, 2020 Category: Drugs & Pharmacology Source Type: research

Risdiplam: First Approval
This article summarizes the milestones in the development of risdiplam leading to this first approval for spinal muscular atrophy. (Source: Drugs)
Source: Drugs - October 12, 2020 Category: Drugs & Pharmacology Source Type: research

Lamivudine/Tenofovir Disoproxil Fumarate is an Appropriate PrEP Regimen
AbstractOral pre-exposure prophylaxis (PrEP) containing tenofovir disoproxil fumarate (TDF) co-formulated with emtricitabine (FTC) or lamivudine (3TC) is recommended as an additional prevention option for persons at substantial risk of HIV infection by both the World Health Organization (WHO) and the US President ’s Emergency Plan for AIDS Relief (PEPFAR). The WHO and PEPFAR consider 3TC clinically interchangeable with FTC for PrEP given comparable pharmacologic equivalence, resistance and toxicity patterns, and indirect clinical trial evidence from TDF-containing studies. Globally, FTC/TDF has been widely used in cl...
Source: Drugs - October 10, 2020 Category: Drugs & Pharmacology Source Type: research

A Narrative Review of Aspirin Resistance in VTE Prophylaxis for Orthopaedic Surgery
AbstractTotal hip arthroplasties (THA) and total knee arthroplasties (TKA) confer one of the highest risks for developing venous thromboembolism (VTE) and pharmacological prophylaxis is imperative to help mitigate the risks. Aspirin is the most cost-effective medication for VTE prophylaxis, and its use post-THA/TKA has grown in popularity. Aspirin resistance is categorised as clinical or laboratory resistance with obesity, advancing age, diabetes mellitus, dyslipidaemia and inflammatory diseases identified as risk factors for aspirin resistance. Treatment failure due to aspirin resistance has been reported in cardiovascula...
Source: Drugs - October 9, 2020 Category: Drugs & Pharmacology Source Type: research

Clascoterone: First Approval
This article summarizes the milestones in the development of clascoterone le ading to this first approval for the topical treatment of acne vulgaris. (Source: Drugs)
Source: Drugs - October 7, 2020 Category: Drugs & Pharmacology Source Type: research

Multifaceted Beneficial Effects of Erdosteine: More than a Mucolytic Agent
AbstractErdosteine is a drug approved for the treatment of acute and chronic pulmonary diseases, originally developed as a mucolytic agent. It belongs to the thiol-based family of drugs that are known to also possess potentially important antioxidant and anti-inflammatory properties, and exhibit antibacterial activity against a variety of medically important bacterial species. Erdosteine is a prodrug that is metabolized to the ring-opening compound metabolite M1 (MET 1), which has mucolytic properties. Experimental studies have documented that erdosteine prevents or reduces lung tissue damage induced by oxidative stress an...
Source: Drugs - October 5, 2020 Category: Drugs & Pharmacology Source Type: research

Oliceridine: First Approval
This article summarizes the milestones in the development of oliceridine leading to this first approval. (Source: Drugs)
Source: Drugs - October 5, 2020 Category: Drugs & Pharmacology Source Type: research

Targeting HER2 in Breast Cancer: Latest Developments on Treatment Sequencing and the Introduction of Biosimilars
AbstractApproximately 20% of all breast cancers overexpress the human epidermal growth factor receptor 2 (HER2). Targeting breast cancer through this vital oncogenic protein has been a major step towards improved patient outcomes. Today, several anti-HER2 agents are in clinical use including: the monoclonal antibodies trastuzumab and pertuzumab; the small molecule inhibitors lapatinib, neratinib, and tucatinib; and the antibody –drug conjugates ado-trastuzumab emtansine and trastuzumab deruxtecan, in some jurisdictions. In addition, several trastuzumab biosimilars have recently been granted regulatory approval in Nor...
Source: Drugs - October 5, 2020 Category: Drugs & Pharmacology Source Type: research

Trastuzumab Emtansine: A Review of Its Adjuvant Use in Residual Invasive HER2-Positive Early Breast Cancer
AbstractTrastuzumab emtansine (Kadcyla®), an antibody –drug conjugate of trastuzumab (Herceptin®) connected by a thioether linker to the microtubule inhibitor DM1 (a cytotoxic derivative of maytansine), provides direct intracellular delivery of the potent cytotoxin DM1 to HER2-overexpressing cells, while retaining trastuzumab activity. Its approval in metastatic/advanced breast cancer (BC) has been extended to include single-agent adjuvant treatment of HER2-positive early BC in patients with residual invasive disease in the breast and/or lymph nodes after neoadjuvant taxane-based and HER2-targeted treatment. ...
Source: Drugs - September 28, 2020 Category: Drugs & Pharmacology Source Type: research

Atezolizumab: A Review in Extensive-Stage SCLC
AbstractAtezolizumab (Tecentriq®), a fully humanized, monoclonal anti-programmed cell death ligand-1 (PD-L1) antibody, is the first immune checkpoint inhibitor to be approved, in combination with carboplatin and etoposide, for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). Approval was based on primary data from the multinational phase I/III IMpower133 trial in PD-L1-unselected patients with previously untreated ES-SCLC. In this trial, induction therapy with atezolizumab plus carboplatin and etoposide followed by maintenance therapy with atezolizumab alone significantly prolonged...
Source: Drugs - September 28, 2020 Category: Drugs & Pharmacology Source Type: research

Correction to: Deprescribing Opioids in Chronic Non ‑cancer Pain: Systematic Review of Randomised Trials
Page 9, Fig.  2, which originally appeared as. (Source: Drugs)
Source: Drugs - September 28, 2020 Category: Drugs & Pharmacology Source Type: research

First-Line Immune Checkpoint Inhibition for Advanced Non-Small-Cell Lung Cancer: State of the Art and Future Directions
AbstractThe advent of PD-(L)1 and CTLA-4 immune check point inhibitors (CPIs) has dramatically changed the treatment landscape of advanced non-small-cell lung cancer (NSCLC). For up to a quarter of patients with advanced NSCLC, CPIs have the potential to induce durable responses with long-term survival outcomes. Since the approval of first-line pembrolizumab for patients whose tumors express a PD-L1 ≥ 50%, several pivotal first-line CPI-based phase 3 studies have been conducted investigating combination treatments combining CPIs with chemotherapy (ChT) or combining different CPIs with or without ChT. As a result, t...
Source: Drugs - September 27, 2020 Category: Drugs & Pharmacology Source Type: research