Shionogi and Co.
Shionogi and Co.
News Article | June 21, 2017
BURTON-ON-TRENT, England--(BUSINESS WIRE)--The fifth paragraph of release dated June 21, 2017 07:00 AM BST should read: "Under this new agreement, Idis GA will supply and distribute argatroban on an exclusive, unlicensed, on demand basis in all countries where there is no Marketing Authorisation or where MTPE has no direct presence." CLINIGEN SIGNS EXCLUSIVE SUPPLY AGREEMENTS IN GLOBAL ACCESS WITH MITSUBISHI TANABE, SHIONOGI AND ROMARK Clinigen Group plc (AIM: CLIN, ‘Clinigen’ or the ‘Group’), the global pharmaceutical and services company, announces that its Idis Global Access (‘Idis GA’) division, has signed three further exclusive agreements to manage the supply and distribution of critical medicines on demand. The three agreements and relevant territories are: The new agreement with MTPE builds on the current relationship with Clinigen’s Idis Managed Access division to provide early access to argatroban where the product has no regulatory approval. Argatroban is indicated for anticoagulation in adult patients with heparin-induced thrombocytopenia type II (‘HIT’) who require parenteral antithrombotic therapy. Under this new agreement, Idis GA will supply and distribute argatroban on an exclusive, unlicensed, on demand basis in all countries where there is no Marketing Authorisation or where MTPE has no direct presence. The agreement with Shionogi is to provide healthcare professional’s access to Senshio® in Germany. Senshio, prescribed in tablet form, is indicated for the treatment of moderate to severe symptomatic vulvar and vaginal atrophy (‘VVA’) in post-menopausal women who are not candidates for local vaginal oestrogen therapy. Idis GA will make Senshio available on an on demand basis to physicians and pharmacists in Germany where the product is approved but not commercially available, and in the UK where the product is approved and has been commercially launched. Idis GA signed a two year extension for the exclusive supply and distribution of Romark’s Alinia® into all territories outside of the US and Latin America. Alinia is indicated for the treatment of diarrhoea in children caused by intestinal infection by the parasites, Cryptosporidium parvum or Giardia lamblia. Idis GA is the market leader in providing hospital pharmacists with compliant on demand access to medicines. Healthcare professionals can obtain details about any of the products mentioned above by emailing firstname.lastname@example.org. Steve Glass, Chief Commercial Officer, North America and Europe, of Clinigen said: “These exclusive agreements demonstrate Idis Global Access’ ability to support international pharma companies, such as Mitsubishi, Shionogi and Romark, to meet on demand access for their medicines. These three varied contracts, including the conversion of a Managed Access programme, demonstrate the positive steps we are taking in building this business to become the go-to leader in ethical access to unlicensed or unavailable medicine.”
Clotet B.,University of Vic |
Feinberg J.,University of Cincinnati |
Van Lunzen J.,Universitatsklinikum Hamburg Eppendorf |
Khuong-Josses M.-A.,Hopital Delafontaine |
And 10 more authors.
The Lancet | Year: 2014
Background Dolutegravir has been shown to be non-inferior to an integrase inhibitor and superior to a non-nucleoside reverse transcriptase inhibitor (NNRTI). In FLAMINGO, we compared dolutegravir with darunavir plus ritonavir in individuals naive for antiretroviral therapy. Methods In this multicentre, open-label, phase 3b, non-inferiority study, HIV-1-infected antiretroviral therapy-naive adults with HIV-1 RNA concentration of 1000 copies per mL or more and no resistance at screening were randomly assigned (1:1) to receive either dolutegravir 50 mg once daily or darunavir 800 mg plus ritonavir 100 mg once daily, with investigator-selected tenofovir.emtricitabine or abacavir.lamivudine. Randomisation was stratifi ed by screening HIV-1 RNA (.100 000 or >100 000 copies per mL) and nucleoside reverse transcriptase inhibitor (NRTI) selection. The primary endpoint was the proportion of patients with HIV-1 RNA concentration lower than 50 copies per mL (Food and Drug Administration [FDA] snapshot algorithm) at week 48 with a 12% non-inferiority margin. This trial is registered with ClinicalTrials.gov, NCT01449929. Findings Recruitment began on Oct 31, 2011, and was completed on May 24, 2012, in 64 research centres in nine countries worldwide. Of 595 patients screened, 484 patients were included in the analysis (242 in each group). At week 48, 217 (90%) patients receiving dolutegravir and 200 (83%) patients receiving darunavir plus ritonavir had HIV-1 RNA of less than 50 copies per mL (adjusted diff erence 7E1%, 95% CI 0E9.13E2), non-inferiority and on pre-specifi ed secondary analysis dolutegravir was superior (p=0E025). Confi rmed virological failure occurred in two (<1%) patients in each group; we recorded no treatment-emergent resistance in either group. Discontinuation due to adverse events or stopping criteria was less frequent for dolutegravir (four [2%] patients) than for darunavir plus ritonavir (ten [4%] patients) and contributed to the diff erence in response rates. The most commonly reported (.10%) adverse events were diarrhoea (dolutegravir 41 [17%] patients vs darunavir plus ritonavir 70 [29%] patients), nausea (39 [16%] vs 43 [18%]), and headache (37 [15%] vs 24 [10%]). Patients receiving dolutegravir had signifi cantly fewer low-density lipoprotein values of grade 2 or higher (11 [2%] vs 36 [7%]; p=0E0001). Interpretation Once-daily dolutegravir was superior to once-daily darunavir plus ritonavir. Once-daily dolutegravir in combination with fixed-dose NRTIs represents an effective new treatment option for HIV-1-infected, treatment-naive patients. Funding ViiV Healthcare and Shionogi & Co. © Chataway et al. Open Access article distributed under the terms of CC BY.
Fujioka M.,Shionogi and Co. |
Omori N.,Shionogi and Co.
Drug Discovery Today | Year: 2012
Therapeutic effects through G protein-coupled receptors (GPCRs) are promoted by a full agonist, partial agonist, neutral antagonist or inverse agonist. Dramatic change of function such as from a neutral antagonist to a full agonist with minimal variation of ligand structure is a phenomenon that medicinal chemists often encounter. This is also influenced by a change of assay format. The subtle nature of structure-function relationships is difficult to grasp unless carefully considered from both chemistry and assay perspectives. In this article we discuss the subtle aspects of GPCR drug discovery from the medicinal chemistry perspective. © 2012 Elsevier Ltd.
Onishi M.,Shionogi and Co. |
Kamimori H.,Shionogi and Co.
Biological and Pharmaceutical Bulletin | Year: 2013
In the present study, we developed a high-throughput and sensitive assay for interactions of amphotericin B (AmB) with two model lipid membranes, which mimicked mammal cell membrane and fungal membrane using surface plasmon resonance (SPR). The binding kinetics of AmB to the membrane could be analyzed by multiple sensorgrams obtained at different AmB concentrations, indicating that the binding properties could be clarified for an approximately 7-fold concentration range. AmB showed an approximately 18-fold higher affinity for ergosterol-containing membrane than for cholesterol-containing membrane. We also optimized the procedure for the reproducible immobilization of liposome containing the sterols and the estimation of binding kinetics of AmB to the lipid membranes, and the sensitivity of AmB to membrane interaction was 20-fold higher, compared with the reported method. The throughput of the established method for the binding kinetics characterization was calculated to be 10 compounds a day. The results demonstrate that the established SPR method could be a valuable tool for predicting selective binding to sterol-containing membranes. © 2013 The Pharmaceutical Society of Japan.
Tonomura Y.,Shionogi and Co. |
Tsuchiya N.,Shionogi and Co. |
Torii M.,Shionogi and Co. |
Uehara T.,Shionogi and Co.
Toxicology | Year: 2010
Since nephrotoxicity affects the development of drug candidates, it is important to detect their toxicity at an early stage of drug development. In this study, we measured twelve urinary nephrotoxic biomarkers [total protein, albumin, kidney injury molecule-1 (KIM-1), clusterin, β2-microglobulin, cystatin-c, alpha-glutathione S-transferase, mu-glutathione S-transferase, N-acetyl-β-d-glucosaminidase, lactate dehydrogenase (LDH), aspartate aminotransferase and neutrophil gelatinase-associated lipocalin (NGAL)] and two conventional blood nephrotoxic biomarkers (creatinine and blood urea nitrogen) in rat models treated intravenously with puromycin aminonucleoside (PAN) or cisplatin (CDDP), which are known to induce glomerular injury or proximal tubular injury, respectively, and evaluated their usefulness by receiver operating characteristic analysis. In the PAN-treated rats, urinary albumin and (NGAL) were dramatically increased, which were thought to be caused by the dysfunction of proximal tubule in addition to glomerular injury. Conversely, based on its early and time-dependent increase, its large magnitude of alteration and its high accuracy and sensitivity of detection, (KIM-1) in urine appeared to be the best biomarker for detection of CDDP-induced proximal tubular injury. Moreover, (LDH) was considered useful for broad detection of damaged nephrons, because of its broad distribution along the nephron. Therefore, combinatorial measurement of these biomarkers may be a powerful tool for highly effective screening of nephrotoxicity. © 2010 Elsevier Ireland Ltd.
Kido Y.,University of California at San Francisco |
Kido Y.,Shionogi and Co. |
Matsson P.,University of California at San Francisco |
Matsson P.,Uppsala University
Journal of Medicinal Chemistry | Year: 2011
Drug-drug interactions (DDIs) are major causes of serious adverse drug reactions. Most DDIs have a pharmacokinetic basis in which one drug reduces the elimination of a second drug, leading to potentially toxic drug levels. As a major organ of drug elimination, the kidney represents an important site for DDIs. Here, we screened a prescription drug library against the renal organic cation transporter OCT2/SLC22A2, which mediates the first step in the renal secretion of many cationic drugs. Of the 910 compounds screened, 244 inhibited OCT2. Computational analyses revealed key properties of inhibitors versus noninhibitors, which included overall molecular charge. Four of six potential clinical inhibitors were transporter-selective in follow-up screens against additional transporters: OCT1/SLC22A1, MATE1/SLC47A1, and MATE2-K/SLC47A2. Two compounds showed different kinetics of interaction with the common polymorphism OCT2-A270S, suggesting a role of genetics in modulating renal DDIs. © 2011 American Chemical Society.
Osato H.,Shionogi and Co. |
Jones I.L.,Institute of Chemical and Engineering Sciences, Singapore |
Chen A.,Institute of Chemical and Engineering Sciences, Singapore |
Chai C.L.L.,Institute of Chemical and Engineering Sciences, Singapore
Organic Letters | Year: 2010
"Chemical Equation Presented" An efficient formal synthesis of oseltamivir phosphate (Tamiflu) has been achieved in 12 steps with use of the inexpensive and highly abundant D-ribose as the starting material. This concise alternative route does not utilize protecting groups and features the introduction of 3-pentylidene ketal as the latent 3-pentyl ether, the use of a highly efficient RCM reaction to form the Tamiflu skeleton, and selective functional group manipulations. © 2010 American Chemical Society.
Sugaya N.,Keiyu Hospital |
Kohno S.,Nagasaki University |
Ishibashi T.,Shionogi and Co. |
Wajima T.,Shionogi and Co. |
Takahashi T.,Keio University
Antimicrobial Agents and Chemotherapy | Year: 2012
Peramivir is a new neuraminidase inhibitor for intravenous administration that was first introduced in clinical practice in Japan. We conducted a multicenter, open-label, uncontrolled study in children with influenza virus infection ranging in age from ≥28 days to < 16 years during the 2009 pandemic A (H1N1) influenza epidemic to evaluate the efficacy, safety, and pharmacokinetics of peramivir in children after intravenous infusion of 10 mg/kg (600 mg maximum) once daily. Among the 106 children (125 days to 15 years old) confirmed to have been infected with the pH1N1 virus by the PCR who were treated with peramivir, the median time to alleviation of symptoms was 29.1 h (95% confidence interval = 22.1 to 32.4), and the proportion of the 106 children who were virus positive was 78.2% on day 2 after the start of treatment and had decreased to 7.1% on day 6. The results of the safety evaluation among 117 patients enrolled in this study showed that adverse events and adverse drug reactions were reported in 62.4 and 29.1%, respectively, of the patients. All of the adverse events and adverse drug reactions resolved or improved rapidly. A population pharmacokinetic analysis was performed on the basis of 297 observed plasma concentration data obtained from 115 children with influenza virus infection. Peramivir exposure in children was within the range of levels within which the efficacy and safety was confirmed in adults, and it is considered that peramivir is clinically and virologically effective and safe in children with pH1N1 virus infection. Copyright © 2012, American Society for Microbiology. All Rights Reserved.
Hasegawa T.,Shionogi and Co.
Pharmaceutical Statistics | Year: 2014
In recent years, immunological science has evolved, and cancer vaccines are available for treating existing cancers. Because cancer vaccines require time to elicit an immune response, a delayed treatment effect is expected. Accordingly, the use of weighted log-rank tests with the Fleming-Harrington class of weights is proposed for evaluation of survival endpoints. We present a method for calculating the sample size under assumption of a piecewise exponential distribution for the cancer vaccine group and an exponential distribution for the placebo group as the survival model. The impact of delayed effect timing on both the choice of the Fleming-Harrington's weights and the increment in the required number of events is discussed. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.
Matsui T.,Hokkaido University |
Yamane J.,Hokkaido University |
Yamane J.,Shionogi and Co. |
Mogi N.,Hokkaido University |
And 4 more authors.
Acta Crystallographica Section D: Biological Crystallography | Year: 2012
FtsZ is a key molecule in bacterial cell division. In the presence of GTP, it polymerizes into tubulin-like proto-filaments by head-to-tail association. Protofilaments of FtsZ seem to adopt a straight or a curved conformation in relation to the bound nucleotide. However, although several bacterial and archaeal FtsZ structures have been determined, all of the structures reported previously are considered to have a curved conformation. In this study, structures of FtsZ from Staphylo-coccus aureus (SaFtsZ) were determined in apo, GDP-bound and inhibitor-complex forms and it was found that SaFtsZ undergoes marked conformational changes. The accumulated evidence suggests that the GDP-bound structure has the features of the straight form. The structural change between the curved and straight forms shows intriguing similarity to the eukaryotic cytoskeletal protein tubulin. Furthermore, the structure of the apo form showed an unexpectedly large conformational change in the core region. FtsZ has also been recognized as a novel target for antibacterial drugs. The structure of the complex with the inhibitor PC190723, which has potent and selective antistaphylococcal activity, indicated that the inhibitor binds at the cleft between the two subdomains. © 2012 International Union of Crystallography Printed in Singapore - all rights reserved.