Amifampridine to treat Lambert-Eaton myasthenic syndrome.
Authors: Oh SJ Abstract Lambert-Eaton myasthenic syndrome (LEMS) is a presynaptic autoimmune disabling neuromuscular disease caused by antibodies against presynaptic voltage-gated calcium channels. It reduces the quantal release of acetylcholine (Ach), causing muscle weakness, reduced or absent reflex and dysautonomia. About half of LEMS patients have associated small cell lung cancer. For symptomatic treatment, amifampridine (3,4-diaminopyridine [3,4-DAP]) is ideal because it increases the release of Ach at the presynaptic membrane. Since the first use of 3,4-DAP in LEMS patients in the 1980s, 136 LEMS patients we...
Source: Drugs of Today - November 18, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Osilodrostat: 11 β-hydroxylase inhibitor for treatment of Cushing's disease.
Osilodrostat: 11β-hydroxylase inhibitor for treatment of Cushing's disease. Drugs Today (Barc). 2020 Oct;56(10):643-654 Authors: Paton DP Abstract Osilodrostat was synthesized in a search for a drug that would inhibit the synthesis of aldosterone, with the aim to discover a new approach for treating hypertension. However, early clinical trials revealed that the doses that could be used for this purpose were limited because osilodrostat was also inhibiting the synthesis of cortisol. Osilodrostat is in fact an inhibitor of both the cytochrome P450 (CYP) enzymes 11β-hydroxylase (CYP11B1) and ald...
Source: Drugs of Today - November 18, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Pretomanid for the treatment of pulmonary tuberculosis.
Authors: Thakare R, Dasgupta A, Chopra S Abstract Discovering novel drugs active against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is currently one of the most unmet medical needs. In this context, pretomanid (PA-824), a novel nitroimidazole prodrug that targets both replicating and nonreplicating cells, is being developed by TB Alliance under license from Novartis. In replicating Mtb, pretomanid inhibits mycolic acid biosynthesis, which is an important building block of Mtb cell wall. Under nonreplicating conditions, pretomanid is reduced by deazaflavin-dependent nitroreductase, l...
Source: Drugs of Today - November 18, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Trabectedin for the therapy of ovarian cancer.
Authors: Evangelisti G, Barra F, D'Alessandro G, Tantari M, Stigliani S, Della Corte L, Bifulco G, Ferrero S Abstract Trabectedin is a marine-derivate antitumor drug with a relevant cytotoxic activity and good safety profile. It has been investigated for the treatment of solid diseases, including ovarian cancer (OC), breast cancer, and soft-tissue sarcoma. In 2009, results from the pivotal trial OVA-301 led the European Medicines Agency (EMA) to the approval of trabectedin in combination with PEGylated liposomal doxorubicin for the treatment of platinum-sensitive recurrent OC; further studies revealed an additional...
Source: Drugs of Today - November 18, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Title.
Authors: Agrawal VR Abstract XXX. PMID: 33185632 [PubMed - in process] (Source: Drugs of Today)
Source: Drugs of Today - November 18, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Golodirsen for Duchenne muscular dystrophy.
This article summarizes golodirsen's pharmacology, efficacy and safety information. It also discusses some controversies that golodirsen met after the approval. PMID: 33025945 [PubMed - in process] (Source: Drugs of Today)
Source: Drugs of Today - October 9, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Peficitinib hydrobromide to treat rheumatoid arthritis.
Authors: Gutiérrez-Ureña SR, Amaya-Cabrera EL, Uribe-Martínez JF, Ventura-Valenzuela ME, Rosal-Arteaga C, Martínez-Bonilla GE, González-Díaz V, Almengor-Montenegro O, Cerpa-Cruz S Abstract Peficitinib hydrobromide is a small Janus kinase inhibitor (JAK1, JAK2, JAK3 and TYK2) molecule for the treatment of rheumatoid arthritis (RA). Phase II and phase III clinical trials and extension studies with different doses have been conducted to assess the drug's efficacy and safety with substantially improved outcomes observed in RA. This JAK inhibitor oral drug demonstrated clinical ...
Source: Drugs of Today - October 9, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Tapinarof to treat psoriasis.
Authors: Rodríguez Baisi K, Tollefson M Abstract There is a need for new and effective topical treatment options for psoriasis. Recent phase I and II clinical trials have demonstrated efficacy of the novel nonsteroidal drug tapinarof to treat mild to moderate plaque psoriasis. Tapinarof is an aryl hydrocarbon receptor (AHR) agonist that induces antioxidant, immunomodulatory and epidermal differentiation regulation pathways. In this review, we examine the current preclinical and clinical studies with a focus on the mechanism of action, pharmacokinetics, safety and efficacy of tapinarof to treat psoriasis. ...
Source: Drugs of Today - October 9, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Zanubrutinib: a new BTK inhibitor for treatment of relapsed/refractory mantle cell lymphoma.
Authors: Weaver AN, Jimeno A Abstract Mantle cell lymphoma (MCL) has historically been an aggressive disease with poor long-term survival. In the last decade, Bruton tyrosine kinase (BTK) inhibition has emerged as a new treatment strategy for MCL, especially in the relapsed/refractory (r/r) setting. Zanubrutinib, a second-generation BTK inhibitor, was approved by the U.S. Food and Drug Administration (FDA) in late 2019 for r/r MCL on the basis of combined overall response rate of 84% in a total of 118 patients from two multicenter clinical trials, BGB-3111-AU-003 and BGB-3111-206. Duration of response was 14-18 mon...
Source: Drugs of Today - October 9, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Drug Information Association (DIA) 2020 Virtual Global Annual Meeting (June 14-18, 2020).
This report covers various presentations and panel discussions from the 4-day meeting that focus on COVID-19, innovative trial designs spurred by a need to adapt amid a pandemic, digital health, novel products inspiring new regulatory standards, clinical trials, data collection and management, the need for more and better data and the ever-increasing importance of the patient perspective. PMID: 33025949 [PubMed - in process] (Source: Drugs of Today)
Source: Drugs of Today - October 9, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Avapritinib for metastatic or unresectable gastrointestinal stromal tumors.
Authors: Alzofon N, Jimeno A Abstract Avapritinib is a tyrosine kinase inhibitor (TKI) that has recently received Food and Drug Administration (FDA) approval for the treatment of metastatic or unresectable gastrointestinal stromal tumors harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation. Mutations in the activation loop of PDGFRA or KIT confer resistance to conventional TKIs due to structural changes in the receptor. Avapritinib was developed to selectively target these mutations, thereby offering a new treatment option for patients in whom imatinib, sunitinib, and regorafenib have...
Source: Drugs of Today - October 9, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Bempedoic acid: effect of ATP-citrate lyase inhibition on low-density lipoprotein cholesterol and other lipids.
Authors: Paton DM Abstract Bempedoic acid is a new, first-in-class oral ATP-citrate lyase (ACLY) inhibitor that has to be converted to its CoA thioester before it inhibits ACLY. This conversion only occurs in the liver and not in skeletal muscle. This may explain why, unlike the statins, bempedoic acid does not cause myalgia. Bempedoic acid given at a dosage of 180 mg orally once daily produces a highly significant reduction in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B and importantly also in high-sensitivity C-reactive protein. It has...
Source: Drugs of Today - October 9, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Levonadifloxacin arginine salt to treat acute bacterial skin and skin structure infection due to S. aureus including MRSA.
Authors: Saxena D, Kaul G, Dasgupta A, Chopra S Abstract Acute bacterial skin and skin structure infections (ABSSSIs) are one of the most common types of infections due to methicillin-resistant Staphylococcus aureus (MRSA). The standard of care for ABSSSI includes glycopeptides such as vancomycin, teicoplanin, oxazolidinones and fluoroquinolones, which are potent broad-spectrum antibacterial agents. Unfortunately, due to indiscriminate utilization, resistance to these agents is rising and identification of novel agents is an urgent unmet medical need. In this context, levonadifloxacin (WCK-771) is a novel, hydrate ...
Source: Drugs of Today - October 9, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

An update on ripasudil for the treatment of glaucoma and ocular hypertension.
Authors: Testa V, Ferro Desideri L, Della Giustina P, Traverso CE, Iester M Abstract Ripasudil (K-115) is a novel Rho-associated protein kinase (ROCK) inhibitor. The Rho-ROCK pathway regulates key downstream effectors involved in many cellular functions, in particular in the actin cytoskeleton activity. The clinical effects of ripasudil expected on the eye include an intraocular pressure-lowering effect and a wound-healing activity on corneal endothelial cells, but many other functions are currently under investigation. To date, ripasudil has been approved in Japan (2014) for the treatment of glaucoma and ocular hy...
Source: Drugs of Today - October 9, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Drug Information Association (DIA) Europe - 32nd Annual Meeting, Virtual (June 29-July 3, 2020).
This report covers some of the sessions held on these 5 days of state-of-the-art topic discussions. PMID: 33025954 [PubMed - in process] (Source: Drugs of Today)
Source: Drugs of Today - October 9, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Diroximel fumarate to treat multiple sclerosis.
Authors: Wang Y, Bhargava P Abstract On October 29, 2019, the Food and Drug Administration (FDA) of the United States approved diroximel fumarate (DRF) as an oral fumarate for the treatment of relapsing forms of multiple sclerosis. Another oral fumarate, dimethyl fumarate (DMF), was approved for the same indication on March 27, 2013. Prior to its approval, DRF did not undergo rigorous testing to determine its efficacy, as its active metabolite, monomethyl fumarate, is the same as that of DMF (bioequivalency). The efficacy, safety and tolerability of DMF have previously been demonstrated in a number of clinical tria...
Source: Drugs of Today - July 12, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Emapalumab for the treatment of hemophagocytic lymphohistiocytosis.
Authors: Cheloff AZ, Al-Samkari H Abstract Emapalumab-Igsz (Gamifant) is a human monoclonal antibody directed against interferon-γ (IFN-γ), and the first Food and Drug Administration (FDA)-approved therapy for primary hemophagocytic lymphohistiocytosis (HLH). HLH is a disorder characterized by hypercytokinemia in the setting of unbridled immune activation, and emapalumab represents the first therapeutic developed to address the underlying pathophysiology of HLH. Emapalumab is approved for treatment of primary HLH that is refractory, recurrent, progressing or intolerant to current HLH treatments in both ...
Source: Drugs of Today - July 12, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Luspatercept to treat β-thalassemia.
Luspatercept to treat β-thalassemia. Drugs Today (Barc). 2020 Jul;56(7):447-458 Authors: Pilo F, Angelucci E Abstract Recently, after years of research often characterized by disappointments and frustrations, finally a new drug impacting on pathological human erythropoiesis has been developed and approved. This drug, luspatercept-aamt (Reblozyl), proved to be effective in both malignant and nonmalignant disease characterized by ineffective erythropoiesis with consequent life-threatening severe anemia. Moreover, for the first time, a medication demonstrated efficacy and effectiveness in β-thal...
Source: Drugs of Today - July 12, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Ubrogepant to treat migraine.
Authors: Dhir A Abstract Migraine is the primary headache disorder affecting a significant population worldwide. Ubrogepant is an orally bioavailable calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) approved by the U.S. Food and Drug Administration (FDA) for the acute treatment of migraine headaches with or without aura in adults. Ubrogepant is the first oral CGRP receptor antagonist approved for the acute treatment of migraine. CGRP is an important key mediator of migraine pain; CGRP levels have been shown to be significantly higher during a migraine attack. Two pivotal phase III clinical trials...
Source: Drugs of Today - July 12, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Progress and current status of molecule-targeted therapy and drug resistance in gastric cancer.
Authors: Chen Z, Li Y, Tan B, Zhao Q, Fan L, Li F, Zhao X Abstract Gastric cancer is one of the most common malignant tumors in the world. In China, its morbidity and mortality are second only to lung cancer. Chemotherapy combined with targeted therapy brings survival benefits to patients with advanced gastric cancer. Targets for targeted therapy of gastric cancer include human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR) and Claudin 18.2 (CLDN 18.2). The main challenge of tumor molecule-targ...
Source: Drugs of Today - July 12, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Alpelisib to treat breast cancer.
Authors: Copur MS Abstract Phosphatidylinositol 3-kinase (PI3K) catalytic subunit p110α (PIK3CA) mutations occur in approximately 40% of patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Alpelisib, a selective oral inhibitor of PI3K, with inhibitory activity predominantly against PIK3CA, has shown synergistic antitumor activity with endocrine therapy against hormone receptor-positive PIK3CA-mutated breast cancer cells in preclinical and early-phase clinical trials. The combination of alpelisib with fulvestrant or an aromatase inhibitor such as let...
Source: Drugs of Today - June 12, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Lascufloxacin hydrochloride to treat bacterial infection.
Authors: Thakare R, Singh S, Dasgupta A, Chopra S Abstract Lascufloxacin hydrochloride (AM-1977) is a novel 8-methoxy fluoroquinolone antibacterial agent with a unique pharmacophore at the 1st and 7th positions of the quinoline nucleus developed by Kyorin Pharmaceutical Co., Ltd. (Tokyo, Japan). It has been approved by the Japanese Ministry of Health, Labour and Welfare (MHLW) for treatment of respiratory tract and ear, nose and throat infections including community-acquired pneumonia and otorhinolaryngological infections, and shows great promise against fluoroquinolone-resistant strains of major pathogens which in...
Source: Drugs of Today - June 12, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Tazemetostat for the treatment of multiple types of hematological malignancies and solid tumors.
Authors: Marsh S, Jimeno A Abstract Epigenetic alterations contributing to malignancy have become a more prominent field of investigation over the past several years, as several hallmarks of cancer are substantially altered by changes in the epigenome. Enhancer of zeste homologue 2 (EZH2), an enzyme involved in silencing the transcription of various genes, is overexpressed or mutated in multiple cancers and can lead to proliferation of dedifferentiated cells. Both gain-of-function and loss-of-function mutations have been noted in hematologic cancers, with gain-of-function mutations prevalent among non-Hodgkin lymph...
Source: Drugs of Today - June 12, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Treosulfan in combination with fludarabine as part of conditioning treatment prior to allogeneic hematopoietic stem cell transplantation.
Authors: Ussowicz M Abstract The combination of treosulfan with fludarabine (Treo-Flu) is one of the new megatherapies prior to hematopoietic stem cell transplantation. Preclinical studies have documented the myeloablative and myelosuppressive effects of treosulfan, in addition to its immunosuppressive and antimalignant activities. Treosulfan pharmacokinetics involves nonenzymatic activation and generation of epoxides as active compounds. In the clinical studies, the most common adverse effects of Treo-Flu were grade 4 hematologic toxicities with leukopenia, neutropenia and thrombocytopenia. Among the most common n...
Source: Drugs of Today - June 12, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Emergence of dual antiretroviral therapy as a viable regimen option for the treatment of patients with HIV infection.
Authors: Fida M, Mahmood M, Temesgen Z Abstract Current antiretroviral therapy is not curative. The need for life-long therapy brings with it concerns regarding long-term toxicity and cost. Thus, investigations into simpler regimens with comparable efficacy and improved safety have been undertaken and continue to be conducted. Various 2-drug combinations have been evaluated with variable results. The combinations of dolutegravir plus lamivudine and dolutegravir plus rilpivirine were found to be comparable in efficacy to conventional 3-drug regimens and have now been approved by the United States Food and Drug Admin...
Source: Drugs of Today - June 12, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Apremilast to treat oral ulcers in Beh çet syndrome.
Apremilast to treat oral ulcers in Behçet syndrome. Drugs Today (Barc). 2020 May;56(5):303-310 Authors: Yazici H Abstract Apremilast, an oral small molecule, is a phosphodiesterase 4 (PDE-4) blocker. It has been shown to be efficacious in managing psoriasis (PS) and psoriatic arthritis (PSA). In two controlled studies, it was also effective in controlling oral ulcers of Behçet syndrome (Bsy). The main side effects associated with apremilast are diarrhea, nausea and headaches. These are usually transient and apremilast requires almost no laboratory monitoring during its use. An important i...
Source: Drugs of Today - May 16, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

An update on conbercept to treat wet age-related macular degeneration.
Authors: Ferro Desideri L, Traverso CE, Nicolò M Abstract Wet age-related macular degeneration (w-AMD) represents the main cause of vision loss in the elderly in the western countries. The important role displayed by vascular endothelial growth factor (VEGF) in the pathogenesis of this disease has been largely demonstrated. For this reason, anti-VEGF drugs have been developed and currently are considered as the first-line treatment options in the management of w-AMD. Among the novel anti-VEGF agents studied, conbercept is a fusion protein composed of the combination between VEGF receptor domains with the Fc ...
Source: Drugs of Today - May 16, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Drospirenone: a novel progestogen used as an oral contraceptive without an estrogen component.
Authors: Paton DM Abstract Drospirenone (DRSP) was synthesized as an analogue of spironolactone with the aim of producing a fourth-generation progestogen that differed from earlier progestogens in that it had antiandrogenic and little or no androgenic activity and lacked estrogenic effects while retaining some antimineralocorticoid activity. Since then, DRSP has been included in several oral contraceptive preparations together with an estrogen. However, increasing evidence has demonstrated that DRSP 4 mg on its own inhibits ovulation. It was thus a logical development to determine the efficacy of a tablet that only...
Source: Drugs of Today - May 16, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Enfortumab vedotin to treat urothelial carcinoma.
Authors: Hanna KS Abstract The antibody-drug conjugate enfortumab vedotin is a fully humanized monoclonal antibody targeting Nectin-4 linked to a microtubule-disrupting agent, monomethyl auristatin E, via a protease-cleavable maleimidocaproyl valine-citrulline linker. In this article, we provide a comprehensive review of the preclinical and clinical activity of enfortumab vedotin, which has been recently approved in the U.S. for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have previously received a programmed cell death protein 1 (PD-1)/programmed cell death 1 ligand...
Source: Drugs of Today - May 16, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Plitidepsin to treat multiple myeloma.
Authors: Gomes NGM, Valentão P, Andrade PB, Pereira RB Abstract While remaining relatively rare, multiple myeloma (MM) accounts for approximately 10% of all hematological malignancies, being an insidious disease with an overall 5-year survival rate of 52%. In addition to other associated complications, myeloma bone disease further aggravates MM patients, the majority of whom suffer from lytic lesions, leading to pain, fractures, mobility issues and neurological deficits. Patients not responding or becoming resistant to prior therapies have now a novel therapeutic tool with an unprecedent mode of action, diff...
Source: Drugs of Today - May 16, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Cenobamate for the treatment of focal epilepsy.
Authors: Dhir A Abstract Focal-onset or partial seizures are localized to a specific brain area or areas of the cerebral hemisphere. Cenobamate (CNB, Xcopri, YKP-3089; SK Life Science) is a recent U.S. Food and Drug Administration (FDA)-approved drug for the treatment of focal-onset seizures in the adult population. CNB has demonstrated broad-spectrum efficacy in alternative preclinical models of epilepsy. The molecule exerts an antiseizure effect due to its dual mechanism of action: besides inhibiting the voltage-gated persistent component of the sodium currents, CNB is additionally an allosteric GABA(A) channel m...
Source: Drugs of Today - April 22, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Imipenem/cilastatin sodium/relebactam fixed combination to treat urinary infections and complicated intra-abdominal bacterial infections.
Authors: Thakare R, Dasgupta A, Chopra S Abstract Imipenem/cilastatin sodium/relebactam is a combination of imipenem/cilastatin, a U.S. Food and Drug Administration (FDA)-approved antibiotic, and β-lactamase inhibitor relebactam which has been developed for the treatment of complicated urinary tract infection (cUTI) and complicated intra-abdominal infection (cIAI) due to drug-resistant bacterial pathogens. The combination (Recarbrio) has been designated as a qualified infectious disease product (QIDP) and obtained FDA approval in 2019 for the treatment of cUTI and cIAI caused by susceptible Gram-negative micro...
Source: Drugs of Today - April 22, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

L-Glutamine in sickle cell disease.
Authors: Cox SE, Hart E, Kirkham FJ, Stotesbury H Abstract L-Glutamine is a conditionally essential amino acid required for synthesis of the pyridines for nucleotides, including nicotinamide adenine dinucleotide (NAD) and glutathione, as well as glutamate, and becomes essential during oxidative stress exposure. The NADH:[NAD⁺ + NADH] (redox) ratio in sickle red blood cells (RBCs) is lower than in normal RBCs, consistent with oxidative stress, therefore glutamine availability is important in sickle cell disease (SCD). RBC glutamine levels vary between SCD studies but the ratio glutamine:glutamate was inversely rel...
Source: Drugs of Today - April 22, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Oliceridine, a G protein-selective ligand at the μ-opioid receptor, for the management of moderate to severe acute pain.
Oliceridine, a G protein-selective ligand at the μ-opioid receptor, for the management of moderate to severe acute pain. Drugs Today (Barc). 2020 Apr;56(4):269-286 Authors: Gan TJ, Wase L Abstract Oliceridine is a next-generation investigational intravenous opioid that is a G protein-selective agonist at the μ-opioid receptor. The G protein selectivity of this compound results in potent analgesia with substantially reduced recruitment of β-arrestin, a signaling pathway associated with opioid-related adverse events. In randomized, placebo- and active-controlled clinical studies, use of olicer...
Source: Drugs of Today - April 22, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Polatuzumab vedotin to treat relapsed or refractory diffuse large B-cell lymphoma, in combination with bendamustine plus rituximab.
Authors: Amaya ML, Jimeno A, Kamdar M Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common non Hodgkin lymphoma (NHL) in adults, and it accounts for about 30% of adult NHL cases. Newly diagnosed patients are treated with rituximab in combination with anthracycline-containing chemotherapy, but a significant number of patients relapse after initial treatment. New strategies for relapsed lymphomas are in development among which antibody-drug conjugates (ADCs) are currently in clinical trials. Polatuzumab vedotin is a novel ADC which binds to the commonly expressed B-cell antigen CD79b, and it delivers mon...
Source: Drugs of Today - April 22, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Cefiderocol to treat complicated urinary tract infection.
Authors: McCarthy MW Abstract On November 14, 2019, the U.S. Food and Drug Administration (FDA) approved cefiderocol, a siderophore-cephalosporin conjugate antibiotic, for the treatment of adults with complicated urinary tract infections (cUTIs), including kidney infections caused by susceptible Gram-negative microorganisms, who have limited or no alternative treatment options. The approval was based on substantial preclinical and clinical data, including in vitro and in vivo work, as well as pharmacokinetic and pharmacodynamic studies that established cefiderocol as an effective agent for the treatment of cUTI. Th...
Source: Drugs of Today - April 14, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Darolutamide for treatment of castration-resistant prostate cancer.
Authors: Rhea LP, Mendez-Marti S, Aragon-Ching JB Abstract Darolutamide is a novel, nonsteroidal androgen receptor (AR)-signaling inhibitor. It serves as a second-generation antiandrogen and is currently indicated for the treatment of patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). The product was approved by the United States Food and Drug Administration (FDA) in July 2019 and by the Japanese Ministry of Health, Labour and Welfare (MHLW) in January 2020 for the treatment of men with nmCRPC, and is awaiting approval in the E.U. for the same indication. This review will cover the backgroun...
Source: Drugs of Today - April 14, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Ropeginterferon alfa-2b for the treatment of patients with polycythemia vera.
Authors: Wagner SM, Melchardt T, Greil R Abstract Ropeginterferon alfa-2b is a novel mono-PEGylated alfa interferon. It is the first interferon approved for the treatment of patients with polycythemia vera (PV) and the first and only approved treatment for PV independent of previous hydroxyurea exposure. In contrast to other interferons, the drug has to be subcutaneously injected every 2 weeks only, with intervals of 4 weeks being possible after prolonged use. It is generally well tolerated and can lead to deep molecular responses. In this article, we provide a review of available preclinical and clinical data of r...
Source: Drugs of Today - April 14, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Tenapanor for constipation-predominant irritable bowel syndrome.
This article will elaborate on the clinical development program for tenapanor for this indication. PMID: 32282867 [PubMed - as supplied by publisher] (Source: Drugs of Today)
Source: Drugs of Today - April 14, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

MicroRNAs and microbiota: Is there a cross talk?
Authors: Rizk M, Tüzmen S Abstract MicroRNAs (miRNAs) are a form of single-stranded RNA molecules with a length that varies between 18 and 23 nucleotides and which are synthesized in the nucleus but function in the cytoplasm. miRNAs function endogenously and bind to complementary sequences in either the coding regions or the 3' untranslated regions (UTRs) of target messenger RNAs (mRNAs). This indicates that miRNAs operate in a post-transcriptional manner. miRNAs play essential roles in various biological events, and have thus been found extracellularly in different body fluids such as saliva, urine and plasma...
Source: Drugs of Today - April 14, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Doravirine: a new non-nucleoside reverse transcriptase inhibitor for the treatment of HIV infection.
Authors: Talwani R, Temesgen Z Abstract Doravirine is a new non-nucleoside reverse transcriptase inhibitor (NNRTI) that was approved by the United States Food and Drug Administration (FDA) on August 30, 2018, for the treatment of HIV infection in adult patients. The product was also approved in the E.U. and Japan in November 2018 and January 2020, respectively. It is currently available as a single stand-alone tablet as well as part of a single-tablet regimen in a fixed-dose combination with tenofovir disoproxil and lamivudine. Similarly to other NNRTIs, doravirine exerts its antiviral effect through a noncompetiti...
Source: Drugs of Today - March 14, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Istradefylline: adenosine A2A receptor antagonist to reduce "OFF" time in Parkinson's disease.
Istradefylline: adenosine A2A receptor antagonist to reduce "OFF" time in Parkinson's disease. Drugs Today (Barc). 2020 Feb;56(2):125-134 Authors: Paton DM Abstract Parkinson's disease (PD) is an extremely common degenerative disease with a progressive course. Unfortunately, the longer patients are treated with levodopa, the more likely they are to suffer from increasingly long periods of immobility or "OFF" time. For over 30 years Kyowa Kirin Co., Ltd. (formerly Kyowa Hakko Kirin Co., Ltd.) has been researching the possibility of finding drugs that affect adenosine receptors and th...
Source: Drugs of Today - March 14, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Mirogabalin besylate in the treatment of neuropathic pain.
Authors: Burgess J, Javed S, Frank B, Malik RA, Alam U Abstract Neuropathic pain (NeP) is a global cause of suffering and debilitation leading to significant morbidity and reduced quality of life. New treatments are needed to address the growing prevalence of NeP and its impact on sleep, mood and functionality. Mirogabalin besylate (mirogabalin, Tarlige) is a gabapentinoid therapy developed by Daiichi Sankyo which is approved in Japan for the treatment of postherpetic neuralgia and painful diabetic peripheral neuropathy. Mirogabalin has a potent pain-modulating effect with a unique high affinity and prolonged disso...
Source: Drugs of Today - March 14, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

JAK inhibitors in chronic plaque psoriasis: What is known so far.
Authors: Plachouri KM, Georgiou S Abstract Janus kinase (JAK) inhibitors are novel small molecules with a mechanism of action in multiple signaling pathways that allows their application in a broad spectrum of autoimmune and autoinflammatory diseases. As far as the field of dermatology is concerned, chronic plaque psoriasis is currently one of the most studied indications regarding the potential use of JAK inhibitors. The purpose of this review is to provide a summarized overview of the existing information on the efficacy and safety of JAK inhibitors in plaque psoriasis, with a focus on tofacitinib, ruxolitinib, b...
Source: Drugs of Today - March 14, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Medicines for Europe - 13th Pharmacovigilance Conference (January 29, 2020 - Amsterdam, the Netherlands).
Authors: Hamaui Cuadrado S Abstract This year, following the European Medicines Agency (EMA) relocation due to the Brexit process, the 13th Pharmacovigilance Conference organized by Medicines for Europe took place in Amsterdam, the Netherlands. The pharmaceutical industry is usually associated with the development and launch of new drugs for the market, but it is also committed to finding new ways of making existing drugs and processes (e.g., pharmacovigilance [PV]) more efficient and better for patients. In relation to this, a variety of topics were on the agenda at the conference, including updates on the progres...
Source: Drugs of Today - March 14, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Galcanezumab: a humanized monoclonal antibody for the prevention of migraine and cluster headache.
Authors: Ossipov MH, Raffa RB, Pergolizzi JV Abstract Migraine is a common, painful and highly disabling neurological condition that has plagued mankind for millennia, but its pathophysiology remained largely obscure until recently. The clinical success of triptans for treating migraine and the discovery that calcitonin gene-related peptide (CGRP) plays a prominent role in migraine led to increased research interest into this disease. An important improvement has been the development of monoclonal antibodies, including galcanezumab, that bind to CGRP or to its receptor, preventing its activation. Subsequent clinica...
Source: Drugs of Today - February 16, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Ivosidenib to treat adult patients with relapsed or refractory acute myeloid leukemia.
Authors: Pasquier F, Lecuit M, Broutin S, Saada S, Jeanson A, Penard-Lacronique V, de Botton S Abstract Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that convert isocitrate to alpha-ketoglutarate (alphaKG). Somatic point mutations in IDH1/2 that are found in rare distinct subsets of cancers confer a gain of function in cancer cells which results in the accumulation and secretion in vast excess of the oncometabolite D-2-hydroxyglutarate (D-2HG). Overproduction of D-2HG interferes with cellular metabolism and epigenetic regulation, contributing to oncogenesis. High levels of D-2HG inhibi...
Source: Drugs of Today - February 16, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Siponimod to treat secondary progressive multiple sclerosis.
Authors: Gajofatto A, Turatti M Abstract Siponimod fumarate (BAF-312) is a synthetic sphingosine 1- phosphate (S1P) receptor modulator, which exerts immunomodulating effects mediated by B- and T-cell sequestration in secondary lymphoid organs. S1P receptor modulators have consistently shown a significant benefit on relapse rate and other measures of disease activity in patients with relapsing multiple sclerosis (MS), compared with both placebo and active comparator. However, most clinical trials of S1P receptor modulators--as well as other therapies for MS--lack evidence of a significant benefit on disability progr...
Source: Drugs of Today - February 16, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

The year's new drugs and biologics 2019.
Authors: Graul AI, Pina P, Tracy M, Sorbera L Abstract Highlights of our annual review of new approvals and launches on global drug markets include the approval and launch of Trikafta, the most widely applicable treatment to date for cystic fibrosis; approval of the first Ebola vaccine for general (rather than emergency) use; the pilot rollout in three African countries of the world's first malaria vaccine; approval of a new treatment option for multidrug-resistant bacterial infections; and the approval and launch in China of the first new drug to treat Alzheimer's disease in more than a decade. Several new immune ...
Source: Drugs of Today - February 16, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Bictegravir, a novel integrase inhibitor for the treatment of HIV infection.
Authors: Zeuli J, Rizza S, Bhatia R, Temesgen Z Abstract Bictegravir (BIC), a second-generation integrase strand transfer inhibitor (INSTI) approved for HIV treatment in fixed-dose combination with emtricitabine and tenofovir alafenamide, has potent antiviral activity in vitro to wild-type virus and strains with resistance to first-generation INSTIs. As part of combination therapy, BIC's virologic suppression rates in clinical trials are comparable to those of first-line combination antiretroviral drug regimens. BIC has demonstrated a high genetic barrier to resistance development in vitro, can be administered with...
Source: Drugs of Today - December 18, 2019 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research