Exploiter la richesse des banques de données dédiées aux médicaments

Mars 2014

• Médicaments en développement – IMSRESEARCH, ADISINSIGHT

• Brevets – IMSPATENTS

• Essais cliniques – ADISCTI

• Effets secondaires, pharmacoéconomie – ADISNEWS

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Agenda

IMSRESEARCH IMS LifeCycle R&D Focus

• Toutes les phases de développement des médicaments de la découverte au lancement commercial

• 35000 fiches d’identification de médicaments ‒ Noms chimiques, commerciaux, codes laboratoires, Rns (30%)

‒ Classification thérapeutique (Ephmra)

‒ Pharmacologie

‒ Statut du développement pour chaque pays • avec informations détaillées sur les licenses (offres, accords..)

‒ Résumés scientifique et commercial

• Mise à jour hebdomadaire • IMS Health (GB)

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La référence IMSRESEARCH

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ACCESSION NUMBER: 2014:115 IMSRESEARCH SOURCE: R&D Focus, (13 Feb 2014) DOCUMENT NUMBER: 2505964 STATUS: NEW DRUG GENERIC NAME: synthetic hepcidin, La Jolla/INSERM CLASSIFICATION: B6C Other Haematological Agents INDICATION: iron overload ACTION: hormone; peptide HIGHEST DEV. PHASE: Preclinical (20) ENTRY DATE: Entered STN: 14 Feb 2014 Last Updated on STN: 14 Feb 2014 LATEST INFORMATION: 13 February 2014 : On 10 February 2014 La Jolla announced that it has entered into an exclusive, worldwide licensing agreement with INSERM (France) for the development of hepcidin agonists for the treatment chronic iron overload. La Jolla plans to initiate a single-dose, exploratory

phase I trial of synthetically-derived hepcidin during 2014 in patients with transfusion-dependent anemia who have severe chronic iron overload and are intolerant to or have failed chelation therapy.

Classification thérapeutique

CURRENT DEVELOPMENT STATUS: Type | Status |Stage|Region| Indication =======+===========+=====+======+============= Highest|Preclinical|20 | | Phase | | | | -------+-----------+-----+------+------------- Phase |Preclinical|20 |France|iron overload COMPANY INFORMATION: Type |Company |Nationality| Corporation ========+========+===========+================ Licensor|INSERM |France |INSERM (France) --------+--------+-----------+---------------- Licensee|La Jolla|USA |La Jolla (United | | |States) COMMERCIAL SUMMARY: Commercial overview. La Jolla is developing synthetic hepcidin for the treatment of chronic iron overload in patients with transfusion-dependent anemia who are intolerant to or have failed chelation therapy. Preclinical evaluation is ongoing. INSERM (France) and La Jolla entered into a licensing agreement regarding hepcidin agonists in February 2014.

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Stades de développement

Sociétés

R&D progress. **Iron overload** Phase I, La Jolla, USA.---DESIGN:Trial planned - Feb 2014. La Jolla plans to initiate a single-dose, exploratory phase I trial of synthetically-derived hepcidin during 2014 in patients with transfusion-dependent anemia who have severe chronic iron overload and are intolerant to or have failed chelation therapy (La Jolla, FEB 2014). Preclinical, INSERM, France.---DESIGN:Study started - 2013. Preclinical evaluation is under way (La Jolla, FEB 2014). Licensing/Partnering. INSERM (Licensor), La Jolla (Licensee).---Licensing agreement signed, Preclinical - Feb 2014.La Jolla has entered into an exclusive, worldwide license agreement with INSERM (France) for the development of hepcidin agonists for the treatment chronic iron overload in patients who are refractory or intolerant to chelators (La Jolla, FEB 2014). DEVELOPMENT HISTORY: FEB 2014 INSERM, La Jolla licensing agreement signed, . 2013 INSERM Study started (preclinical), France (iron overload)

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Exemple : Identifier les sociétés auxquelles l’Inserm a concédé des licences

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=> S (INSERM (L) LICENSOR)/CO L1 10 (INSERM (L) LICENSOR)/CO => ANA L1 CO L2 ANALYZE L1 1- CO : 27 TERMS => D 1- L2 ANALYZE L1 1- CO : 27 TERMS TERM # # OCC # DOC % DOC CO ------ ------- ------ ------ --------------- 1 12 10 100.00 INSERM 2 10 10 100.00 INSERM (FRANCE) 3 3 2 20.00 BIOPROJET 4 2 2 20.00 BIOPROJET (FRANCE) 5 1 1 10.00 ASSISTANCE PUBLIQUE HOPITAUX DE PARIS (FRANCE) 6 1 1 10.00 ASSISTANCE PUBLIQUE HOPITAUX DE PARIS 7 1 1 10.00 C2X PHARMA (FRANCE) 8 1 1 10.00 C2X PHARMA 9 1 1 10.00 DYAX (UNITED STATES)

COmpany Name

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10 1 1 10.00 DYAX 11 1 1 10.00 GLAXOSMITHKLINE (UK) 12 1 1 10.00 GLAXOSMITHKLINE 13 1 1 10.00 INNAVIRVAX (FRANCE) 14 1 1 10.00 INNAVIRVAX 15 1 1 10.00 INSERM : BIOPROJET 16 1 1 10.00 LA JOLLA (UNITED STATES) 17 1 1 10.00 LA JOLLA 18 1 1 10.00 NOVO NORDISK (DENMARK) 19 1 1 10.00 NOVO NORDISK 20 1 1 10.00 QUANTUM GENOMICS (UNITED STATES) 21 1 1 10.00 QUANTUM GENOMICS 22 1 1 10.00 TCLAND (FRANCE) 23 1 1 10.00 TCLAND 24 1 1 10.00 UNIVERSITE PARIS 5 RENE DESCARTES (FRANCE) 25 1 1 10.00 UNIVERSITE PARIS 5 RENE DESCARTES 26 1 1 10.00 URRMA BIOPHARMA (CANADA) 27 1 1 10.00 URRMA BIOPHARMA ********* END OF L2 ***

Exemple : Offres de licence ou de partenariat pour des agents de diagnostic (classification T diagnostic agents)

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=> HELP T The following Classification Codes may be used with the Classification Code T, e.g., S T1E/CC. For a complete listing of these codes, enter HELP CLASSCODES at an arrow prompt (=>) in the file. T DIAGNOSTIC AGENTS T1A LOW OSMOLAR ANGIO-UROGRAPHY T1C GASTROENTEROGRAPHY T1E MRI AGENTS T1F ULTRASOUND AGENTS T1G RADIODIAGNOSTIC AGENTS T1X OTHER IMAGING AGENTS

=> S T1#/CC L1 410 T1#/CC => S L1 AND (AVAILABLE FOR LICENSING OR AVAILABLE FOR PARTNERING) L2 116 L1 AND (AVAILABLE FOR LICENSING OR AVAILABLE FOR PARTNERING) => S L2/NEW L3 6 L2/NEW

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=> D ALL 1- L3 ANSWER 1 OF 6 IMSRESEARCH COPYRIGHT 2014 IMSWORLD on STN AN 2013:684 IMSRESEARCH SO R&D Focus, (14 Oct 2013) DN 2505641 STA NEW DRUG CN MAb, ER-alpha 36, Shenogen; MAb, estrogen receptor-alpha 36, diagnosis, Shenogen; MAb, estrogen receptor-alpha 36, Shenogen CC T1X Other Imaging Agents CT Indication: diagnosis Pharmacology: protein; monoclonal antibody; biotechnology HDP Preclinical (20) ED Entered STN: 18 Oct 2013 Last Updated on STN: 18 Oct 2013 LI 14 October 2013 : Jun Bao, Senior Vice President and Chief Business Officer of Shenogen, informed R&D Focus at BioJapan 2013, 9-11 October 2013, Yokohama, Japan, that the company is developing a monoclonal antibody targeting estrogen receptor-alpha 36 for the diagnosis of cancer. Preclinical evaluation is under way in China. This program is available for partnering. DSTA Type | Status |Stage| Region |Indication =========+===========+=====+=========+========== Highest |Preclinical|20 | | Phase | | | | ---------+-----------+-----+---------+----------

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---------+-----------+-----+---------+---------- Phase |Preclinical|20 |China |diagnosis ---------+-----------+-----+---------+---------- Licensing|Available | |Worldwide| CO Type |Company |Nationality| Corporation ==========+========+===========+================ Originator|Shenogen|China |Shenogen (China) TX Commercial Summary: Commercial overview. OverviewShenogen is developing a monoclonal antibody targeting estrogen receptor-alpha 36 for the diagnosis of cancer. Preclinical evaluation is under way in China.R&D progress. Preclinical, Shenogen, China.---DESIGN:Study started - 2013. Preclinical evaluation is under way in China (Shenogen, OCT 2013).Licensing/Partnering. Shenogen.---Availability, Preclinical - Oct 2013.Shenogen's monoclonal antibody targeting estrogen receptor-alpha 36 for the diagnosis of cancer is available for partnering (Shenogen, OCT 2013). RDAT: OCT 2013 RNTE: Shenogen partnering opportunity, Worldwide . 2013 Shenogen Study started (preclinical), China (diagnosis) .

ADISINSIGHT Adis R&D Insight

• Toutes les phases de développement des médicaments de la découverte au lancement commercial

• 31000 fiches d’identification de médicaments ‒ Noms chimiques, commerciaux, codes laboratoires, Rns (30%)

‒ Classifications thérapeutiques (EphMRA, WHO)

‒ Pharmacologie, études cliniques

‒ Statut du développement pour chaque pays • avec informations détaillées sur les licenses (offres, accords..)

• Mise à jour hebdomadaire • Springer Adis (US)

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La référence ADISINSIGHT

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ACCESSION NUMBER: 2006:519 ADISINSIGHT SOURCE: Adis R&D Insight DOCUMENT NO: 024329 CHANGE DATE: Dec 4, 2013 GENERIC NAME: Lobeglitazone SYNONYM: CKD 501; CKD-501; IDR-105; Lobeglitazone sulfate CHEMICAL NAME: 2,4-Thiazolidinedione, 5-((4-(2-((6-(4-methoxyphenoxy)-4-pyrimidinyl)

methylamino)ethoxy)phenyl)methyl)-,sulfate (1:1) MOLECULAR FORMULA: C24 H24 N4 O5 S H2 O4 S CAS REGISTRY NO.: 763108-62-9 STRUCTURE: RELATED CAS REG. NO.: 607723-33-1 (Parent drug) EPHMRA ATC CODE: A10X Other Drugs Used in Diabetes WHO ATC CODE: A10B-X Other oral blood glucose lowering drugs, excl. insulins HIGHEST DEV. PHASE: Preregistration CURRENT DEVELOPMENT STATUS: Preregistration, Korea, Democratic People's Republic of,Type-2 diabetes mellitus Phase III, Korea, Democratic People's Republic of, Type-2 diabetes mellitus Preclinical, United States, Type-2 diabetes mellitus

Identification de la molécule

Codes thérapeutiques

Stades de développement

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COMPANY INFORMATION ORIGINATOR: Chong Kun Dang (Korea, Democratic People's Republic of) PARENT: Chong Kun Dang LICENSEE: EQUIS & ZAROO OTHER SOURCES: 801027548; 801105485 WORD COUNT: 983 TEXT Introduction: Lobeglitazone is an orally available, dual peroxisome proliferator-activated receptor alpha/gamma (PPARalpha/gamma) agonist being developed by Chong Kun Dang Pharmaceutical for the treatment of type 2 diabetes mellitus. Lobeglitazone has been filed for approval in South Korea as a monotherapy, and is in phase III development in combination with other anti-diabetes treatments. EQUIS & ZAROO is developing lobeglitazone under license in the US. Development is at the preclinical stage in the US. Company agreements Lobeglitazone was out-licensed to EQUIS & ZAROO in 2007, for development in the US. Key development milestones Chong Kun Dang filed lobeglitazone for approval in South Korea in 2012, as a monotherapy for type 2 diabetes mellitus.

Sociétés

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Chong Kun Dang completed a randomised, double-blind phase III trial in November 2012, to assess the efficacy and safety of lobeglitazone in combination with metformin for 24 weeks in patients with type 2 diabetes mellitus (NCT01106131). The control group received pioglitazone in combination with metformin. The core trial was followed by a 28-week extension to assess long-term safety. The trial enrolled 253 patients in South Korea. In October 2009, Chong Kun Dang initiated a phase III trial to assess the efficacy and safety of lobeglitazone once daily for 24 weeks as a monotherapy for patients with type 2 diabetes (NCT01001611). Patients were randomised to receive placebo or lobeglitazone tablet (0.5mg) once daily for 24 weeks (or 52 weeks if participating in the extension study). Enrolment of 168 patients was completed in November 2010, and the trial was completed in South Korea in January 2012. A phase II study of lobeglitazone for the treatment of type 2 diabetes has been completed in South Korea (NCT01030679). This randomised, double blind, placebo-controlled, parallel assignment study investigated the safety and effectiveness of lobeglitazone in lowering fasting plasma glucose levels in patients with type 2 diabetes, as compared with placebo. The trial enrolled 214 patients. Chong Kun Dang is planning a randomised, crossover phase I trial to investigate the potential pharmacokinetic drug-interaction between lobeglitazone and warfarin in healthy male volunteers (NCT02002611). The trial will enrol 24 subjects in South Korea.

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The company is also planning two open-label phase I clinical trials to evaluate the pharmacokinetics of lobeglitazone in healthy volunteers and subjects with impaired hepatic function (19HI13018; NCT02005744, 19RI113017; NCT02007941). Both trials will be conducted in South Korea, and one trial will enrol 24 subjects and the other trial is intended to enrol 38 subjects. In August 2011, Chong Kun Dang completed a randomised, open-label, crossover phase I trial to assess the pharmacokinetic interaction between lobeglitazone and amlodipine in healthy male volunteers (NCT01341392). The trial enrolled 25 subjects in South Korea. Chong Kun Dang conducted a randomised, open-label, crossover phase I trial to assess the effect of ketoconazole on the pharmacokinetics of lobeglitazone in healthy male volunteers (NCT01330563). The trial enrolled 24 subjects in South Korea and was completed in June 2011. Chong Kun Dang completed two phase I trials of lobeglitazone in August 2010; both trial enrolled 24 volunteers from South Korea. One was a drug-food interaction trial (NCT01071720) and the other was a drug interaction trial evaluating potential interactions between lobeglitazone and glimepiride (NCT01133431). In February 2010, Chong Kun Dang completed a randomised, open-label, three-way crossover phase I trial to investigate the pharmacokinetic interaction between lobeglitazone and metformin in healthy male volunteers (NCT01005160).The trial enrolled 24 subjects in South Korea.

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Lobeglitazone showed favourable oral pharmacokinetics with potential for once-daily dosing. Chong Kun Dang has conducted a phase I study of lobeglitazone in 36 male volunteers that evaluated safety, tolerability and pharmacokinetics/1/. Chong Kun Dang has completed a phase I trial of lobeglitazone (2 and 4mg) in 22 healthy female volunteers in South Korea. Results have been reported from this randomised, placebo-controlled, dose-rising, parallel group study/2/. EQUIS & ZAROO is conducting preclinical development of lobeglitazone in the US Patent information Chong Kun Dang holds US patents covering lobeglitazone, and has pending patent applications for lobeglitazone in 16 countries. PHARMACOLOGY OVERVIEW: Mechanism of action: Peroxisome proliferator-activated receptor gamma agonists Peroxisome proliferator-activated receptor agonists Peroxisome proliferator-activated receptor gamma modulators Transcription factor stimulants Peroxisome proliferator-activated receptor modulators Cytoplasmic and nuclear receptor agonists Transcription factor modulators Protein stimulants Cytoplasmic and nuclear receptor modulators Protein modulators

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Peroxisome proliferator-activated receptor alpha agonists Peroxisome proliferator-activated receptor agonists Transcription factor stimulants Peroxisome proliferator-activated receptor modulators Cytoplasmic and nuclear receptor agonists Transcription factor modulators Protein stimulants Cytoplasmic and nuclear receptor modulators ------------------------------------------ tmax (h) (oral) 0.5 - 4 (unspecified) t (1/2) beta (h) 7.8 - 9.8 (unspecified) ------------------------------------------ Activity versus parent drug: unspecified parent CLINICAL OVERVIEW: Route(s) of Administration: PO Administration Freq.(per day): Drug Interactions: Unknown. Adverse Events: In a phase I study that evaluated lobeglitazone (2 and 4mg) in 22 female volunteers, pharmacokinetic differences were seen with lobeglitazone 4mg when results were compared that of a previously published trial in male volunteers. Despite the pharmacokinetic differences, the tolerability profile of lobeglitazone 4mg was the same in both genders; there was no difference in the number of adverse events reported between women or men.

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PHARMACOLOGY: Pharmacokinetics: Lobeglitazone (2 and 4mg) did not display linear pharmacokinetics in healthy women who participated in a placebo-controlled, phase I study (n = 22). Statistical analysis indicated that the relationship of C sub(max) and AUC was not dose-proportional in female volunteers; lobeglitazone (2 and 4mg) was not associated with dose-proportional C sub(max) (214.8 and 310.0 ug/L, respectively) and AUC (2251.3 and 6942.6 microg x h/L, respectively) in female subjects. Results of this study were also compared with that of a previously published trial in male volunteers. The female : male ratios of C sub(max) and AUC (95% CI) values for lobeglitazone 2mg were 1.23 (0.89, 1.69) and 1.11 (0.73, 1.68), respectively; the corresponding values for lobeglitazone 4mg were

1.28 (1.01, 1.63) and 2.36 (1.60, 3.47), respectively/2/. °° REFERENCES 1. Kim JR, Cho JY, et al. Safety, tolerability and pharmacokinetics of CKD-501, a novel peroxisome proliferator-activated receptor alpha/ gamma dual agonist after oral administration. Clinical Pharmacology and Therapeutics. 79: 39, No. 2, Feb 2006. Summary in 2 parts (Part A). (English). 801027548 2. Lee HE, Kim JW, et al. Pharmacokinetics and safety of CKD-501, a novel PPAR alpha/gamma dual agonist, after oral administration in healthy female subjects. Clinical Pharmacology and Therapeutics. 83 (Suppl. 1): 95, Mar 2008. (English). 801105485

Exemple : Identifier les sociétés qui développent des antinéoplastiques en phase III en France

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=> S ANTINEOPLASTIC#/CC AND (PHASE III (L) FRANCE)/DSTA L1 68 ANTINEOPLASTIC#/CC AND (PHASE III (L) FRANCE)/DSTA => D 1 68 L1 ANSWER 1 OF 68 ADISINSIGHT COPYRIGHT 2014 Wolters Kluwer Pharma on STN ACCESSION NUMBER: 2013:68 ADISINSIGHT SOURCE: Adis R&D Insight CHANGE DATE: Feb 19, 2014 GENERIC NAME: Rituximab biosimilar - Boehringer Ingelheim SYNONYM: BI 695500; BI-695500 CHEMICAL NAME: Immunoglobulin G1, anti-(human CD20 (antigen)(human- mouse monoclonal IDEC-C2B8 gamma1-chain), disulfide with human- mouse monoclonal IDEC-C2B8 kappa-chain, dimer MOLECULAR FORMULA: C6416 H9874 N1688 O1987 S44 CAS REGISTRY NO.: 174722-31-7 EPHMRA ATC CODE: L1X3 Antineoplastic monoclonal antibodies; M1 Anti-Inflammatory and Anti-Rheumatic Products WHO ATC CODE: L01X-C02 Rituximab; M01A-X Other antiinflammatory and antirheumatic agents, non-steroids HIGHEST DEV. PHASE: Phase III COMPANY INFORMATION ORIGINATOR: Boehringer Ingelheim (Germany) PARENT: Boehringer Ingelheim

CC : Classification Code DSTA : Development STAtus

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L1 ANSWER 68 OF 68 ADISINSIGHT COPYRIGHT 2014 Wolters Kluwer Pharma on STN ACCESSION NUMBER: 1998:1695 ADISINSIGHT SOURCE: Adis R&D Insight DOCUMENT NO: 001954 CHANGE DATE: Dec 1, 2013 GENERIC NAME: Tiotropium bromide SYNONYM: BA 679-BR; BA 679BR; BA-679-BR; BA-679BR; Tiotropium; Tiotropium Respimat CHEMICAL NAME: 3-Oxa-9-azoniatricyclo(3,3.1.0(2,4))nonane, 7-((hydroxydi-2-thienylacetyl)oxy)-9,9-dimethyl-, bromide, (1alpha,2beta,4beta,5alpha,7beta)- TRADE NAME: Spiriva(R); Spiriva(R) HandiHaler(R); Spiriva(R) Respimat(R); Tiova(R) MOLECULAR FORMULA: C19 H22 Br N O4 S2 CAS REGISTRY NO.: 139404-48-1 RELATED CAS REG. NO.: 186691-13-4 (Tiotropium) EPHMRA ATC CODE: L1 Antineoplastics; R3G3 Anticholinergics-plain, inhalant; R7 Other Respiratory System Products WHO ATC CODE: L01 Antineoplastic Agents; R03B-B04 Tiotropium bromide; R07 Other Respiratory System Products HIGHEST DEV. PHASE: Launched COMPANY INFORMATION ORIGINATOR: Boehringer Ingelheim (Germany) PARENT: Boehringer Ingelheim LICENSEE: Pfizer

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=> S L1 AND PHASE III/HDP L2 28 L1 AND PHASE III/HDP => ANA L2 CO L3 ANALYZE L2 1- CO : 62 TERMS => D DOC TOP15 L3 ANALYZE L2 1- CO : 62 TERMS TERM # # OCC # DOC % DOC CO ------ ------- ------ ------ --------------- 1 7 4 14.29 NOVARTIS 2 5 3 10.71 AMGEN 3 3 3 10.71 CARDIFF UNIVERSITY 4 3 3 10.71 GENENTECH 5 3 3 10.71 NATIONAL CANCER INSTITUTE (USA) 6 4 2 7.14 BOEHRINGER INGELHEIM 7 3 2 7.14 ROCHE 8 2 2 7.14 ASTELLAS PHARMA 9 2 2 7.14 BAXTER INTERNATIONAL 10 2 2 7.14 CHUGAI PHARMACEUTICAL 11 2 2 7.14 DYAX 12 2 1 3.57 ACTIVE BIOTECH 13 2 1 3.57 ARQULE 14 2 1 3.57 ARRAY BIOPHARMA 15 2 1 3.57 BIOALLIANCE PHARMA 47 MORE TERMS WITH A DOCUMENT COUNT OF 1

HDP : Highest Development Phase

Analyse sur les noms de société (Company name)

Visualisation des 15 premières sociétés classées par nombre de références associées

Exemple : Quels types de médicaments Allergan a-t-il sous licence ?

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=> S ALLERGAN/CO (L) LICENSEE L1 35 ALLERGAN/CO (L) LICENSEE => D L1 ANSWER 1 OF 35 ADISINSIGHT COPYRIGHT 2014 Wolters Kluwer Pharma on STN ACCESSION NUMBER: 2011:486 ADISINSIGHT SOURCE: Adis R&D Insight DOCUMENT NO: 033965 CHANGE DATE: Apr 6, 2011 GENERIC NAME: AC 262271 SYNONYM: AC-262271 MOLECULAR FORMULA:Unspecified EPHMRA ATC CODE: S1E Miotics and Antiglaucoma Preparations WHO ATC CODE: S01E Antiglaucoma Preparations and Miotics HIGHEST DEV. PHASE: Phase I COMPANY INFORMATION ORIGINATOR: ACADIA Pharmaceuticals (United States) PARENT: ACADIA Pharmaceuticals LICENSEE: Allergan

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=> ANA L1 CC L2 ANALYZE L1 1- CC : 89 TERMS => D L2 ANALYZE L1 1- CC : 89 TERMS TERM # # OCC # DOC % DOC CC ------ ------- ------ ------ --------------- 1 5 5 14.29 S1X OTHER OPHTHALMOLOGICALS 2 4 4 11.43 N02 ANALGESICS 3 4 4 11.43 N2 ANALGESICS 4 4 4 11.43 S1E MIOTICS AND ANTIGLAUCOMA PREPARATIONS 5 3 3 8.57 G4D4 URINARY INCONTINENCE PRODUCTS 6 3 3 8.57 S01 OPHTHALMOLOGICALS 7 3 3 8.57 S01E ANTIGLAUCOMA PREPARATIONS AND MIOTICS 8 3 3 8.57 S01X OTHER OPHTHALMOLOGICALS 9 3 3 8.57 S1 OPHTHALMOLOGICALS 10 3 2 5.71 D11A OTHER DERMATOLOGICAL PREPARATIONS

Analyse sur les codes thérapeutiques (Classification Codes)

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=> ANA L1 CC LEN1 L3 ANALYZE L1 1- CC LEN 1 : 11 TERMS => D L3 ANALYZE L1 1- CC LEN 1 : 11 TERMS TERM # # OCC # DOC % DOC CC ------ ------- ------ ------ --------------- 1 46 21 60.00 S 2 23 8 22.86 N 3 17 5 14.29 D 4 9 4 11.43 G 5 9 3 8.57 L 6 8 3 8.57 R 7 4 2 5.71 M 8 2 1 2.86 A 9 2 1 2.86 B 10 2 1 2.86 C 11 2 1 2.86 J ********* END OF L3 ***

A ALIMENTARY TRACT AND METABOLISM B BLOOD AND BLOOD FORMING ORGANS C CARDIOVASCULAR SYSTEM D DERMATOLOGICALS G GENITO-URINARY SYSTEM AND SEX HORMONES H SYSTEMIC HORMONAL PREPARATIONS (EXCLUDING SEX HORMONES) J GENERAL ANTI-INFECTIVES, SYSTEMIC L ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS M MUSCULO-SKELETAL SYSTEM N CENTRAL NERVOUS SYSTEM P PARASITOLOGY R RESPITORY SYSTEM S SENSORY ORGANS T DIAGNOSTIC AGENTS V VARIOUS

Analyse sur les CC (LENgth 1 uniquement le 1er caractère)

ADISINSIGHT / IMSRESEARCH

• Ces 2 banques de données sont souvent les premières sources d’information sur les molécules

• Exemple : Tak 901

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=> INDEX REGISTRY ADISBASES IMSBASES INDEX REGISTRY, ADISCTI, ADISINSIGHT, ADISNEWS, IMSPATENTS, IMSRESEARCH => S (TAK 901 OR TAK901)/CN 1 FILE ADISINSIGHT 1 FILE IMSRESEARCH 2 FILES HAVE ONE OR MORE ANSWERS, 6 FILES SEARCHED IN STNINDEX L1 QUE (TAK 901 OR TAK901)/CN

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=> FILE ADISINSIGHT IMSRESEARCH => S L1 L2 2 L1 => D 1-2 IDE DSTA L2 ANSWER 1 OF 2 ADISINSIGHT COPYRIGHT (C) 2014 Wolters Kluwer Pharma Solutions on STN ACCESSION NUMBER: 2008:1174 ADISINSIGHT SOURCE: Adis R&D Insight DOCUMENT NO: 029358 CHANGE DATE: Mar 5, 2013 GENERIC NAME: TAK 901 CHEMICAL NAME: 5-(3-(Ethylsulfonyl)phenyl)-3,8-dimethyl-N-(1- methylpiperidin-4-yl)-9H-pyrido(2,3-b)indole-7- carboxamide MOLECULAR FORMULA: C28 H32 N4 O3 S EPHMRA ATC CODE: L1 Antineoplastics WHO ATC CODE: L01 Antineoplastic Agents HIGHEST DEV. PHASE: Phase I COMPANY INFORMATION ORIGINATOR: Takeda (Japan) PARENT: Takeda OTHER: Millennium DSTA Phase I, United States, Haematological malignancies Discontinued I, United States, Lymphoma Discontinued I, United States, Solid tumours

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L2 ANSWER 2 OF 2 IMSRESEARCH COPYRIGHT 2014 IMSWORLD on STN ACCESSION NUMBER: 2009:1145 IMSRESEARCH SOURCE: R&D Focus, (15 Dec 2011) DOCUMENT NUMBER: 2032928 LABORATORY NAME: TAK 901 CLASSIFICATION: L1X4 Antineoplastic Protein Kinase Inhibitors HIGHEST DEV. PHASE: Discontinued (2) ENTRY DATE: Entered STN: 21 Aug 2009 Last Updated on STN: 16 Dec 2011 COMPANY INFORMATION: Type |Company|Nationality| Corporation ==========+=======+===========+============== Originator|Takeda |Japan |Takeda (Japan)

DSTA Type | Status |Stage| Region | Indication =======+============+=====+=============+==================== Highest|Discontinued|2 | | Phase | | | | -------+------------+-----+-------------+-------------------- Phase |Discontinued|2 |United States|hematological cancer -------+------------+-----+-------------+-------------------- Phase |Discontinued|2 |United States|lymphoma -------+------------+-----+-------------+-------------------- Phase |Discontinued|2 |United States|solid tumor -------+------------+-----+-------------+-------------------- Phase |Discontinued|2 |Japan |cancer

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=> D ALL 1 L2 ANSWER 1 OF 2 ADISINSIGHT COPYRIGHT (C) 2014 Wolters Kluwer Pharma Solutions on STN AN 2008:1174 ADISINSIGHT SO Adis R&D Insight DN 029358 CDAT Mar 5, 2013 CN TAK 901 °° TX TEXT Introduction: Millennium (a wholly-owned subsidiary of Takeda) is developing TAK 901, an Aurora kinase B inhibitor for the treatment of haematological malignancies. ° ° An open-label, single group assignment phase I trial determined the safety, tolerability and maximum tolerated dose of TAK 901 in patients with haematological malignancies in the US (NCT00807677). The trial enrolled 31 patients and was completed in March 2013. A phase I trial assessing TAK 901 for the treatment of advanced solid tumours or lymphoma was completed in December 2011 (NCT00935844). The trial enrolled 20 patients in the US. Results from studies of TAK 901 in preclinical models of acute myeloid leukaemia were reported in June 2011. °°°

IMSPATENTS IMS LifeCycle Patent Focus

• Brevets de médicaments commercialement importants • Une référence par médicament et par brevet

‒ pour EP et PCT, une référence par état désigné ‒ 262000 références depuis 1995

• Une référence IMSPATENTS mentionne :

‒ Noms commerciaux, noms chimiques ‒ CAS Registry Number ‒ Classifications thérapeutiques (Ephrma) ‒ Phase de développement ‒ Numéros, dates de publication et de dépôt ‒ Dates d’expiration (mention des ccp, des extensions pédiatriques) ‒ Commentaires commerciaux

• Mise à jour mensuelle

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ACCESSION NUMBER: 2013:15908 IMSPATENTS DOCUMENT NUMBER: 406848 FAMILY NUMBER: 10855 SOURCE: Patents International, (4 Jun 2013) ENTRY DATE: Entered STN: 26 Jun 2013 Last updated on STN: 9 Jan 2014 CAS REGISTRY NUMBER: 51333-22-3 GENERIC NAME: budesonide propionate; budesonide (INN) LABORATORY CODE: S 1320 TRADE NAME: BETACTIN; ENTOCORT; ENTOCORT EC; HORACORT; INFLAMMIDE; NARICORT; PREFERID; PULMICORT; RHINOCORT; PULMICORT CHEMICAL NAME: (11beta,16alpha)-16,17-[butylidenebis(oxy)]- 11,21-dihydroxypregna-1,4-diene-3,20-dione DERIVATIVE(S): 51333-22-3 budesonide 126168-43-2 cmpd with gamma-cyclodextrin 2:3) 150693-37-1 mixt with formoterol 150693-38-2 mixt with formoterol fumarate 68707-09-5 replaced by 51372-29-3

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La référence IMSPATENTS

STRUCTURE: CLASSIFICATION: A7E Intestinal Anti-inflammatory Agents; D7A Topical Corticosteroids; R3D Corticoids INDICATION: allergic rhinitis; asthma; Crohn disease; skin disease; ulcerative colitis PHARMACOLOGY: corticosteroid HIGHEST DEV. PHASE: Marketed (80) CORPORATION: AstraZeneca (United Kingdom) PATENT ASSIGNEE: Astra (Sweden) SUPPLEMENTARY TERM: Composition INDEX TERM: Dry powder budesonide compositions - 1997

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PATENT INFORMATION: Publication Patent Publication Filing Expiration Number Type Date Date Date ----------------- ----------- ----------- -------- ---------- EP 1019033 application 20000719 19980113 20180113 EP 1019033 grant 20080319 19980113 20180113 DESIGNATED STATES: United Kingdom PRIORITY INFORMATION: SE 1997-133 19970120 TEXT: Expiry Comments: Granted (2008) Country Comments: EP1019033 B is based on WO9831350 and claims a dry powder composition comprising budesonide and a carrier, both of which comprise particles having a mass median diameter of less than 10 mcm and are uniformly distributed. The composition has a poured bulk density of from 0.28 to 0.38 g/ml ABSTRACT: The patent family listed here claims a dry powder composition comprising budesonide and a carrier and relates to the PULMICORT FLEXHALER formulations of budesonide.

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Exemple : Identifier les sociétés qui détiennent des brevets sur le traitement de la maladie de Crohn (couvrant la France et expirant après 2014)

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=> S CROHN DISEASE AND FR/PCS AND XPY>2014 L1 72 CROHN DISEASE AND FR/PCS AND XPY>2014 => D COTAB 1- L8 IMSPATENTS COPYRIGHT 2014 IMSWORLD on STN. ANS| Patent Assignee | Compound |Publication | | |Number(s) ===+========================+=====================+============ 1|Aptalis (Canada) |5-aminosalicylic acid|EP 2512443 ---+------------------------+---------------------+------------ 2|Abbott (United States) |ustekinumab |EP 2319870 ---+------------------------+---------------------+------------ 3|Abbott (United States) |ustekinumab |EP 2301970 ---+------------------------+---------------------+------------ 4|Abbott (United States) |ustekinumab |EP 2099414 ---+------------------------+---------------------+------------ 5|Abbott (United States) |ustekinumab |EP 1175446 ---+------------------------+---------------------+------------

PCS : pays de publication ou état désigné XPY : année d’expiration

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---+------------------------+---------------------+------------ 6|BioMarin (United States)|BH4 |EP 1845952 ---+------------------------+---------------------+------------ 7|Zeria (Japan) |acotiamide |EP 870765 | | |EP 870765 ---+------------------------+---------------------+------------ 8|Pfizer (United States) |sildenafil |EP 941075 | | |EP 941075 ---+------------------------+---------------------+------------ 9|Pfizer (United States) |sildenafil |EP 941075 | | |EP 941075 ---+------------------------+---------------------+------------ 10|Pfizer (United States) |sildenafil |EP 1097711 | | |EP 1097711 °°°

Exemple : Le Veramyst est-il couvert par des ccp ?

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=> S VERAMYST/CN AND (EXTENSION OR SPC OR CCP) L1 30 VERAMYST/CN AND (EXTENSION OR SPC OR CCP) => D CYTAB 1-10 L1 IMSPATENTS COPYRIGHT 2014 IMSWORLD on STN. ANS|Country |Publication |Expiry |Expiry Comments| NOTE | |Number(s) |Date | | ===+=========================+=============+==========+===============+====== 1|Czech Republic |CZ 20030352 |20210803 |Granted (2013);|1, 2 |Czech Republic |CZ 304043 | |SPC Filed for | | | | |AVAMYS | ---+-------------------------+-------------+----------+---------------+------ 2|Taiwan, Province of China|TW 244486 |20231127 |Granted (2005);|3, 4 | | | |Extension | | | | |Granted | ---+-------------------------+-------------+----------+---------------+------ 3|Spain |EP 1305329 |20210803 |Granted (2007);|5, 6, 7, | |EP 1305329 | |Legal Action; |8 | | | |SPC Granted for| | | | |AVAMYS | ---+-------------------------+-------------+----------+---------------+--------

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---+-------------------------+-------------+----------+---------------+-------- 4|Liechtenstein |EP 1305329 |20210803 |Granted (2007);|5, 6, 9 | |EP 1305329 | |Legal Action; | | | | |SPC Granted for| | | | |AVAMYS | ---+-------------------------+-------------+----------+---------------+-------- 5|Korea, Republic of |KR 2003028806|20210819 |Granted (2008);|10, 11 |Korea, Republic of |KR 827379 | |Extension | | | | |Granted | ---+-------------------------+-------------+----------+---------------+-------- 6|United Kingdom |EP 1305329 |20210803 |Granted (2007);|5, 6, 12 | |EP 1305329 | |Legal Action; | | | | |SPC Granted for| | | | |AVAMYS °°°° 5. EP1305329 B is based on WO0212265 and claims fluticasone furoate specifically, along with its solvates and unsolvated form I, II and III polymorphs. 6. Opposition was filed against EP1305329 B at the European patent office by Norton Healthcare in September 2008, subsequently an appeal was filed in April 2011. °°° 12. A supplementary protection certificate (SPC) for the AVAMYS formulations of fluticasone furoate has been granted in the UK citing EP1305329 B. The SPC expires on 10 January 2023.

IMSPATENTS Les formats tabulaires

CYTAB COTAB CCTAB

Country Patent Assignee Classification code

Publication N° Compound Compound

Expiry date Publication N°

Patent Assignee

Expiry comments

Note

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ADISCTI Adis Clinical Trials Insight

• Information axée sur les essais cliniques • 1700 journaux depuis 1998 • 600000 références bibliographiques

‒ dont 50% CITATION ONLY (BIB + CT)

• Mise à jour hebdomadaire • Springer Adis (Us)

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La référence ADISCTI

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ACCESSION NUMBER: 2014:2557 ADISCTI DOCUMENT NUMBER: 809159798 TITLE: InterMune Reports Phase 3 ASCEND Trial Results of Pirfenidone in Idiopathic Pulmonary Fibrosis (IPF). ADIS TITLE: InterMune Reports Phase 3 ASCEND Trial Results of Pirfenidone in Idiopathic Pulmonary Fibrosis (IPF). AUTHOR: InterMune SOURCE: Media Release (Feb 25, 2014), Vol. in 2 parts (Part A) | , URL: http://www.intermune.com DOCUMENT TYPE: Best Evidence ADIS REC. CREATED: 4 Mar 2014 REFERENCE: Respiratory Tract Disorders LANGUAGE: English WORD COUNT: 364 OTHER SOURCE: ADISINSIGHT 1998006975; ADISINSIGHT 2012001136 ENTRY DATE: Entered STN: 7 Mar 2014 Last Updated on STN: 7 Mar 2014 TEXT - Results Highlights: Efficacy: Pirfenidone was significantly superior to placebo in the treatment of idiopathic pulmonary fibrosis, according to top-line results. Specifically, pirfenidone significantly improved forced vital capacity over 1 year vs placebo (p<0.000001; primary endpoint). It was also significantly superior to placebo in the 6-minute walking test and progression-free survival, key secondary endpoints.

Fiches d’identification AdisInsight

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Tolerability: Pirfenidone was generally tolerated well and had a favourable safety profile in patients with idiopathic pulmonary fibrosis, according to top-line results. TEXT - Author Comments: "We are pleased to report these top-line ASCEND Phase 3 results. Based on the strength of the ASCEND results, InterMune is preparing a resubmission of our New Drug Application for pirfenidone to the U.S. Food and Drug Administration (FDA), which we expect to submit by early third quarter of this year." TEXT - Subject Details: Type: patients Age: 40-80 Years Sex: not stated Location: Australia, Brazil, Croatia, Israel, Mexico, Multinational, New Zealand, Peru, Singapore, USA Disease: Idiopathic-pulmonary-fibrosis Patient Inclusion: 1. Diagnosis of definite or probable Idiopathic Pulmonary Fibrosis (IPF) per the ATS 2011 Guidelines up to 48 months before randomization 2. Age 40 to 80 at randomization 3. Percent Forced Vital Capacity (%FVC) ≥50% and ≤90% at screening 4. Percent Carbon Monoxide Diffusing Capacity (%DLCO) ≥30% and ≤90% at screening Select Patient Exclusion: 1. Forced expiratory volume in one second (FEV1)/FVC ratio 0.8 after administration of bronchodilator at Screening 2. Expected to receive a lung transplant within 1 year from randomization or, for patients at sites in the United States, on a lung transplant waiting list at randomization 3. Known explanation for interstitial lung disease

Informations détaillées sur l’essai clinique

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4. History of asthma or chronic obstructive pulmonary disease 5. Active infection 6. Ongoing IPF treatments including investigational therapy, immunosuppressants, and cytokine modulating agents 7. History of unstable or deteriorating cardiac or pulmonary disease (other than

IPF) within the previous 6 months Pirfenidone -------------------------------------------------------------------- Drug/Treatment Dose Route Frequency Duration -------------------------------------------------------------------- Pirfenidone 2403 mg/day PO tid 1 year -------------------------------------------------------------------- Placebo TEXT - Study Details: Design: double-blind, multicentre, parallel, prospective, randomised Control: baseline comparison, placebo comparison Phase: III Endpoints: Forced-vital-capacity Name: Assessment of Pirfenidone to Confirm Efficacy and Safety in IPF (ASCEND) Companies: InterMune ID: 700241613 (Clinical Trials Insight) NCT01366209 (ClinicalTrials.gov: US National Institutes of Health) PIPF016 (InterMune) CONTROLLED TERM: Drug Descriptors: Pirfenidone, therapeutic use CONTROLLED TERM: Disease Descriptors: Idiopathic pulmonary fibrosis, treatment

• Evaluation, aspects positifs, négatifs des essais cliniques (20% des références)

• Clinical relevance (/CL) A Study provides new evidence of clinical benefit

B Study provides supporting evidence to existing data C Study adds no new or important information

• Pour plus de détails , consulter HELP EVAL

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ADISCTI

Exemple : Cediranib

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=> FILE ADISCTI => E CEDIRANIB/CT E1 2 CEDELIZUMAB, PHARMACOKINETICS/CT E2 3 CEDELIZUMAB, THERAPEUTIC USE/CT E3 157 --> CEDIRANIB/CT E4 70 CEDIRANIB, ADVERSE REACTIONS/CT E5 1 CEDIRANIB, DRUG INTERACTIONS/CT E6 3 CEDIRANIB, PHARMACODYNAMICS/CT E7 17 CEDIRANIB, PHARMACOKINETICS/CT E8 107 CEDIRANIB, THERAPEUTIC USE/CT E9 360 CEFACLOR/CT °° => S CEDIRANIB/CT,TI L1 167 CEDIRANIB/CT => S L1 NOT CITATION-ONLY/DT L2 149 L1 NOT CITATION-ONLY/DT => S L2 AND CL/FA L3 14 L2 AND CL/FA

Elimination des références uniquement bibliographiques

Limitation aux références avec évaluation clinique

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=> D ALL L3 ANSWER 1 OF 14 ADISCTI COPYRIGHT 2014 Wolters Kluwer Pharma on STN AN 2014:1953 ADISCTI DN 803099848 TI LATE BREAKING ABSTRACT: Randomised double-blind phase III trial of cediranib (AZD 2171) in relapsed platinum sensitive ovarian cancer: Results of the ICON6 trial. ADIS TITLE: LATE BREAKING ABSTRACT: Randomised double-blind phase III trial of cediranib (AZD 2171) in relapsed platinum sensitive ovarian cancer: Results of the ICON6 trial. AU Ledermann J A; Perren T J; Raja F A; Embleton A; Rustin GJS; Jayson G; Kaye S B; Swart A M; Vaughan M SO 2013 European Cancer Congress (Sep 27, 2013), pp. abstr. 10, URL: http://eccamsterdam2013.ecco-org.eu/Scientific-Programme/Searchable- Programme.aspx Meeting Info: European Cancer Congress (2013 : September 2013 : Amstderdam, Netherlands) DT Best Evidence DED ADIS Rec Created: 18 Feb 2014 RE Oncology; Women's Health; Genitourinary Disorders LA English WC 1224 OS ADISINSIGHT 1998000730; ADISINSIGHT 1998000759; ADISINSIGHT 1998007957; ED Entered STN: 21 Feb 2014 Last Updated on STN: 21 Feb 2014

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EVAL Adis Comment: Results data from this trial are expected to support regulatory submissions for cediranib to be administered in combination with platinum-based chemotherapy in women with platinum-sensitive relapsed ovarian, fallopian tube or peritoneal cancer in first relapse. CL A TX Results Highlights: Efficacy: Cediranib + platinum-based chemotherapy resulted in a significantly longer median progression-free survival interval, compared with platinum-based chemotherapy alone (11.4 vs 9.4 months; p<0.01; co-primary endpoint), as well as a significantly longer median overall survival duration (20.3 vs 17.6 months; p<0.05; co-primary endpoint) in women with platinum-sensitive relapsed ovarian, fallopian tube or peritoneal cancer in first relapse. Tolerability: °°° CT Drug Descriptors: Carboplatin, adverse reactions; Carboplatin, therapeutic use; Cediranib, therapeutic use; Cediranib, adverse reactions; Gemcitabine, adverse reactions; Gemcitabine, therapeutic use; Paclitaxel, therapeutic use; Paclitaxel, adverse reactions; Platinum complexes, adverse reactions; Platinum complexes, therapeutic use CT Disease Descriptors: Fallopian tube cancer, treatment; Ovarian cancer, treatment; Peritoneal cancer, treatment CT Pharmacoecononic Descriptors: Cost analysis

ADISNEWS 3 Newsletters : • Reactions (alerts to adverse drug reactions from all adverse drug events reported in the world's biomedical literature – 78000 réf.) • Inpharma (alerts to drugs and drug therapy – 40000 réf.) • Pharmacoeconomics & Outcomes News (health economics news – 20000 réf.)

• Limitation à la newsletter “Reactions” pour les alertes de pharmacovigilance

=> S SIMVASTATIN L1 1357 SIMVASTATIN => S L1 AND REACTIONS/FS L2 712 L1 AND REACTIONS/FS

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FS : File Segment

La référence ADISNEWS

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=> D IALL ACCESSION NUMBER: 2014:1494 ADISNEWS ENTRY DATE: Entered STN: 13 Mar 2014 Last Updated on STN: 13 Mar 2014 DOCUMENT NUMBER: 01149954-803100534 TITLE: ADR news: Lisinopril/lithium. Azotaemia and transcortical motor aphasia in an elderly patient: case report. Serious. SOURCE: REACTIONS 12 Mar 2014 ISSN: 0114-9954 TEXT: A 65-year-old man developed transient transcortical motor aphasia due to lithium toxicity during treatment for bipolar affective disorder type 1 [time to reaction onset not stated]; the toxicity was attributed to a combination of factors including high lithium dosing after recent weight loss and dehydration with prerenal azotaemia whilst receiving lisinopril [therapeutic indication and time to reaction onset not stated]. The man's history included hypertension, chronic obstructive pulmonary disease, coronary artery disease, remote myocardial infarction with coronary stenting and implantable defibrillator placement, ischaemic cardiomyopathy (ejection fraction 20-25%), and a left ventricular thrombus; he had undergone left below-knee amputation and was unsteady on his feet. His medications were oral lithium 300mg three times daily, oral lisinopril 10 mg/day, metoprolol, aspirin, warfarin, spironolactone, simvastatin, gabapentin, sildenafil and a prostate health supplement. He presented with worsening confusion, word-finding difficulty and a tremor, following a fall in which he hit his head. His wife reported he had progressive mild memory impairment and difficulty finishing his )

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sentences and finding words for the previous few days. His family also reported a weight loss of 20 pounds over the previous 6 months. He reported polydypsia and polyuria of several days' duration. His wife had noted increased exertion over the past week with inadequate hydration. Examination revealed a moderate bilateral tremor in his upper limbs at rest and with purposeful movement; he had no paresis. He was oriented to place and person but not to time or season. He had slow speech with delayed initiation and he had difficulty with word finding but his thought process did not appear illogical or tangential. Comprehension was intact, but he was unable to recite his daughters' or wife's names and could not say where he lived. His handwriting was illegible. Serum lithium level was supratherapeutic (1.9 mEq/L) and INR was subtherapeutic (1.42). The man was hospitalised for lithium toxicity and assessment for possible stroke; lithium was withdrawn. °°°° REFERENCE(S): (1) Katz, R. B.; Packer, C. D. Lithium toxicity presenting as transient transcortical motor aphasia: A case report. Psychosomatics 2014, V55, P87-91 (English, Case report (USA)) CONTROLLED TERM: Aphasia, drug-induced; Elderly; Lisinopril, serious adverse-reactions; Lithium, serious adverse-reactions; Uraemia, drug-induced CAS REGISTRY NO.: 50-78-2 (ASPIRIN) 52-01-7 (SPIRONOLACTONE) 81-81-2 (WARFARIN) 7439-93-2 (LITHIUM) 79902-63-9 (SIMVASTATIN) 139755-83-2 (SILDENAFIL)

La référence originale

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=> E SIMVASTATIN/CT E1 1 SIMETHICONE, SERIOUS DRUG-INTERACTIONS/CT E2 7 SIMETHICONE, THERAPEUTIC-USE/CT E3 0 --> SIMVASTATIN/CT E4 146 SIMVASTATIN, ADVERSE-REACTIONS/CT E5 32 SIMVASTATIN, DRUG-INTERACTIONS/CT E6 1 SIMVASTATIN, GENERAL/CT E7 62 SIMVASTATIN, PHARMACODYNAMICS/CT E8 7 SIMVASTATIN, PHARMACOKINETICS/CT E9 123 SIMVASTATIN, SERIOUS ADVERSE-REACTIONS/CT E10 98 SIMVASTATIN, SERIOUS DRUG-INTERACTIONS/CT E11 2 SIMVASTATIN, SERIOUS OVERDOSE/CT E12 329 SIMVASTATIN, THERAPEUTIC-USE/CT => S E4-E5 OR E9-E11 L3 395 ("SIMVASTATIN, ADVERSE-REACTIONS"/CT OR "SIMVASTATIN, DRUG-INTER ACTIONS"/CT) OR ("SIMVASTATIN, SERIOUS ADVERSE-REACTIONS"/CT OR "SIMVASTATIN, SERIOUS DRUG-INTERACTIONS"/CT OR "SIMVASTATIN, SERIOUS OVERDOSE"/CT) => D ALL

Vocabulaire contrôlé Controlled Term

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L1 ANSWER 1 OF 395 ADISNEWS COPYRIGHT 2014 Adis Data Information BV on STN AN 2014:987 ADISNEWS ED Entered STN: 19 Feb 2014 Last Updated on STN: 26 Feb 2014 DN 01149954-803099718 TI ADR news: Simvastatin. Recurrent colonic dilatation and volvulus in an elderly patient: case report. Serious. SO REACTIONS 19 Feb 2014 ISSN: 0114-9954 TX A 70-year-old man man developed recurrent colonic dilatation and volvulus while receiving simvastatin. About 6 months after starting simvastatin 40mg [route, frequency and indication not stated] the man developed symptoms of abdominal discomfort and a persistent sensation of being unable to fully open his bowels. The man was admitted to hospital a total of 14 times in 6 years with these symptoms. At each visit, abdominal x-rays demonstrated a sigmoid volvulus, with no mechanical cause apparent on colonoscopy and CT scans. He initially underwent a laparoscopic sigmoid colectomy, with a good postoperative recovery. However, he returned with the same symptoms after 2 years. Simvastatin was held, and his symptoms markedly improved. He was able to open his bowels daily with no discomfort. However, following the man's admission to hospital for investigation of weakness, simvastatin was inadvertently recommenced. His symptoms reappeared, and abdominal x-rays showed dilated loops of large bowel. Simvastatin was stopped, and he was initiated on ezetimibe. At review several months later, he confirmed the continued ease and frequency at which he could open his bowels.

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Author Comment: "Implementation of [the Naranjo] probability scale yielded a score of 6, which correlates to a probable adverse drug reaction association [for simvastatin]". RE (1) Fernandes, R.; Shaikh, I.; Wegstapel, H. Possible association between statin use and bowel dysmotility. BMJ Case Reports 2012, V2012, P[3 pages] (English, Case report (United Kingdom)) CT Elderly; Intestinal-disorders, drug-induced; Intestinal-obstruction, drug-induced; Simvastatin, serious adverse-reactions RN 79902-63-9 (SIMVASTATIN)

=> S SIMVASTATIN L1 1357 SIMVASTATIN => S L1 AND REACTIONS/FS L2 712 L1 AND REACTIONS/FS => S E4-E5 OR E9-E11 L3 395 ("SIMVASTATIN, ADVERSE-REACTIONS"/CT OR "SIMVASTATIN, DRUG-INTERACTIONS"/CT) OR ("SIMVASTATIN, SERIOUS ADVERSE-REACTIONS"/CT OR "SIMVASTATIN, SERIOUS DRUG-INTERACTIONS"/CT OR "SIMVASTATIN, SERIOUS OVERDOSE"/CT)

AN 2014:1120 ADISNEWS ED Entered STN: 25 Feb 2014 Last Updated on STN: 27 Feb 2014 DN 11735503-803100085 TI Statin intensification rates low in US hospitals. SO PHARMACOECONOMICS AND OUTCOMES NEWS 25 Feb 2014 ISSN: 1173-5503 TX Rates of statin initiation in patients hospitalised with an acute myocardial infarction (AMI) are high in US hospitals, but rates of statin intensification and maximisation are low. These are the main findings of a large prospective study that used data from 4271 patients from 24 US hospitals to examine statin prescription patterns on admission and discharge.* The data analysis showed that 87% of patients who were statin naive on presentation for their AMI and had no contraindication for statin therapy were started on a statin during hospitalisation, most commonly atorvastatin (47%) or simvastatin (39%)°°°°°. RE (1) Arnold, S. V.; Kosiborod, M.; Tang, F.; Zhao, Z.; Maddox, T. M.; McCollam, P. L.; Birt, J.; Spertus, J. A. Patterns of Statin Initiation, Intensification, and Maximization Among Patients Hospitalized with an Acute Myocardial Infarction. Circulation 2014, P4 Feb 2014. Available from (English, Study (USA)) CT Drug-utilisation; HMG-CoA-reductase-inhibitors, therapeutic-use; Myocardial-infarction, treatment; Prescribing RN 79902-63-9 (SIMVASTATIN) 134523-00-5 (ATORVASTATIN) 147098-20-2 (ROSUVASTATIN)

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Une référence de pharmaéconomie

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Les banques de données ADIS ou IMS sont des sources d’ information incontournables sur les sociétés pharmaceutiques et les molécules qu’elles développent . Elles permettent de retrouver des informations détaillées sur - les stades de développement, les licences (Adisinsight, Imsresearch) - les brevets, les certificats complémentaires de protection (Imspatents) - les essais cliniques (Adiscti) - les effets secondaires (Adisnews)

Martine MICHEL martine.michel@capadoc.fr

www.capadoc.com

www.stn-international.com www.cas.org

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