DOCSLIB.ORG

Parsabiv H-3995

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

15 September 2016 EMA/664198/2016 Committee for Medicinal Products for Human Use (CHMP) Assessment report Parsabiv International non-proprietary name: etelcalcetide Procedure No. EMEA/H/C/003995/0000 Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. 30 Churchill Place ● Canary Wharf ● London E14 5EU ● United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5520 Send a question via our website www.ema.europa.eu/contact An agency of the European Union © European Medicines Agency, 2016. Reproduction is authorised provided the source is acknowledged. Table of contents 1. Background information on the procedure .............................................. 6 1.1. Submission of the dossier ..................................................................................... 6 1.2. Steps taken for the assessment of the product ........................................................ 7 2. Scientific discussion ................................................................................ 8 2.1. Introduction ........................................................................................................ 8 2.1.1. Problem statement ............................................................................................ 8 2.1.2. About the product ............................................................................................. 9 2.2. Quality aspects .................................................................................................... 9 2.2.1. Introduction...................................................................................................... 9 2.2.2. Active Substance ............................................................................................. 10 General information .................................................................................................. 10 Manufacture, characterisation and process controls ....................................................... 10 Specification ............................................................................................................ 11 Stability................................................................................................................... 12 2.2.3. Finished Medicinal Product ................................................................................ 12 Manufacture of the product and process controls .......................................................... 13 Product specification ................................................................................................. 13 Stability of the product .............................................................................................. 14 Adventitious agents .................................................................................................. 15 2.2.4. Discussion on chemical, pharmaceutical and biological aspects.............................. 15 2.2.5. Conclusions on the chemical, pharmaceutical and biological aspects ...................... 15 2.2.6. Recommendations for future quality development ............................................... 15 2.3. Non-clinical aspects ............................................................................................ 15 2.3.1. Introduction.................................................................................................... 15 2.3.2. Pharmacology ................................................................................................. 15 2.3.3. Pharmacokinetics ............................................................................................ 17 2.3.4. Toxicology ...................................................................................................... 20 2.3.5. Ecotoxicity/environmental risk assessment ......................................................... 23 2.3.6. Discussion on non-clinical aspects ..................................................................... 23 2.3.7. Conclusion on non-clinical aspects ..................................................................... 25 2.4. Clinical aspects .................................................................................................. 25 2.4.1. Introduction.................................................................................................... 25 2.4.2. Pharmacokinetics ............................................................................................ 26 2.4.3. Pharmacodynamics .......................................................................................... 28 2.4.4. Discussion on clinical pharmacology ................................................................... 32 2.4.5. Conclusions on clinical pharmacology ................................................................. 32 2.5. Clinical efficacy .................................................................................................. 33 2.5.1. Dose response studies ..................................................................................... 33 2.5.2. Main studies ................................................................................................... 33 2.5.3. Discussion on clinical efficacy ............................................................................ 55 Assessment report EMA/664198/2016 Page 2/98 2.5.4. Conclusions on clinical efficacy .......................................................................... 60 2.6. Clinical safety .................................................................................................... 61 2.6.1. Discussion on clinical safety .............................................................................. 80 2.6.2. Conclusions on clinical safety ............................................................................ 83 2.7. Risk Management Plan ........................................................................................ 83 2.8. Pharmacovigilance ............................................................................................. 87 2.9. Product information ............................................................................................ 87 2.9.1. User consultation ............................................................................................ 87 2.9.2. Additional monitoring ....................................................................................... 87 3. Benefit-Risk Balance ............................................................................. 87 Discussion on the benefit-risk assessment ................................................................... 95 4. Recommendations ................................................................................. 97 Assessment report EMA/664198/2016 Page 3/98 List of abbreviations ADME absorption, distribution, metabolism, excretion AMG 416 Etelcalcetide AUC area under the concentration-time curve BDC bile duct cannulated BSAP bone specific alkaline phosphatase CaSR calcium-sensing receptor cCA corrected calcium cCa x P corrected calcium-phosphorus product CI confidence interval CKD Chronic Kidney Disease CMH Cochran-Mantel-Haenszel CPP Critical process parameter CQA Critical quality attribute CTX collagen C-telopeptide DOPPS Dialysis Outcomes and Practice Patterns Study EAP efficacy assessment period EC European Commission EMA European Medicines Agency ERA-EDTA European Renal Association–European Dialysis and Transplant Association ESRD end-stage renal disease EU European Union EVOLVE EValuation Of Cinacalcet Therapy to Lower CardioVascular Events, Study 20050182 FGF-23 fibroblast growth factor-23 FMEA Failure mode effects analysis FMoc Fluorenylmethyloxycarbonyl GC Gas Chromatography GLP Good Laboratory Practice GMP Good Manufacturing Practice HPLC High performance liquid chromatography SHPT Secondary Hyperparathyroidism IC Ion chromatography ICH International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use IPC In-process control ICP-MS Inductively coupled plasma mass spectrometry IV Intravenous JP Japanese Pharmacopoeia KDIGO Kidney Disease: Improving Global Outcomes KDOQI Kidney Disease Outcome Quality Initiative KF Karl Fischer titration LE Long Evans MedDRA Medical Dictionary for Regulatory Activities NMR Nuclear Magnetic Resonance NOAEL no observed adverse effect level NOE Nuclear Overhauser Effect P Phosphorus Ph. Eur. European Pharmacopoeia PIP Paediatric Investigation Plan Assessment report EMA/664198/2016 Page 4/98 PK Pharmacokinetics PRO patient reported outcome PTG parathyroid gland PTH parathyroid hormone PVC Poly vinyl chloride QbD Quality by design QD once daily QTc corrected QT interval QTcF Fridericia-corrected QT interval RH Relative Humidity RTU ready to use SAP statistical analysis plan SAPC serum albumin peptide conjugate SC Subcutaneous SD Sprague Dawley SD standard deviation SE standard error SmPC Summary of Product Characteristics SMQ Standardized Medical Dictionary for Regulatory Activities Queries TFA trifluoroacetic acid TIW three times a week TK Toxicokinetics USP United States Pharmacopoeia UV/Vis Ultraviolet/visible spectroscopy WFI Water for injections Assessment report EMA/664198/2016 Page 5/98 1. Background information on the procedure 1.1. Submission of the dossier The applicant Amgen Europe B.V. submitted on 2 September 2015 an application for Marketing Authorisation to the European Medicines Agency (EMA) for Parsabiv, through the centralised procedure under Article 3(2)(a) of
Recommended publications
  • WO 2013/096741 A2 27 June 2013 (27.06.2013) P CT

    WO 2013/096741 A2 27 June 2013 (27.06.2013) P CT

    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2013/096741 A2 27 June 2013 (27.06.2013) P CT (51) International Patent Classification: (74) Agents: GEORGE, Nikolaos C. et al; Jones Day, 222 A61K 35/12 (2006.01) East 41st Street, New York, NY 10017-6702 (US). (21) International Application Number: (81) Designated States (unless otherwise indicated, for every PCT/US20 12/07 1192 kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (22) Date: International Filing BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, 2 1 December 2012 (21 .12.2012) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (25) Filing Language: English HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, (26) Publication Language: English ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, (30) Priority Data: NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, 61/579,942 23 December 201 1 (23. 12.201 1) US RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, 61/592,350 30 January 2012 (30.01.2012) US TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, 61/696,527 4 September 2012 (04.09.2012) us ZM, ZW. (71) Applicant: ANTHROGENESIS CORPORATION (84) Designated States (unless otherwise indicated, for every [US/US]; 33 Technology Drive, Warren, NJ 07059 (US).
  • PARSABIV (Etelcalcetide) RATIONALE for INCLUSION IN

    PARSABIV (Etelcalcetide) RATIONALE for INCLUSION IN

    PARSABIV (etelcalcetide) RATIONALE FOR INCLUSION IN PA PROGRAM Background Parsabiv (etelcalcetide) is a calcimimetic agent that increases the sensitivity of the calcium-sensing receptor to activation by extracellular calcium. These calcium-sensing receptors are on the parathyroid hormone gland and are the principal regulators of PTH (parathyroid hormone) synthesis and secretion. By increasing the sensitivity of the calcium sensing receptors, a reduction in PTH secretion is achieved. Reductions in PTH are associated with a decrease in bone turnover and bone fibrosis in patients with CKD (chronic kidney disease) on hemodialysis and uncontrolled secondary hyperparathyroidism (HPT) (1). Regulatory Status FDA approved indication: Parsabiv is a calcium-sensing receptor agonist indicated for treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis (1). Limitation of Use: Parsabiv has not been studied in adult patients with parathyroid carcinoma, primary hyperparathyroidism, or with CKD who are not on hemodialysis and is not recommended for use in these populations (1). Initial treatment with Parsabiv is contraindicated if serum calcium is less than the lower limit of the normal range. Life threatening events and fatal outcomes were reported due to hypocalcemia. Hypocalcemia can prolong QT interval, lower the threshold for seizures, and cause hypotension, worsening heart failure, and/or arrhythmia. Monitor serum calcium carefully for the occurrence of hypocalcemia during treatment. Once the maintenance dose has been established, serum calcium should be measured monthly for patients with secondary hyperparathyroidism with CKD on hemodialysis (1). In patients with secondary hyperparathyroidism with chronic kidney disease who are on hemodialysis, serum calcium should be measured within 1 week of starting Parsabiv, and intact parathyroid hormone (iPTH) should be measured 4 weeks after initiation or dose adjustment of Parsabiv (1).
  • Parsabiv, INN-Etelcalcetide

    Parsabiv, INN-Etelcalcetide

    ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 1. NAME OF THE MEDICINAL PRODUCT Parsabiv 2.5 mg solution for injection Parsabiv 5 mg solution for injection Parsabiv 10 mg solution for injection 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Parsabiv 2.5 mg solution for injection Each vial contains 2.5 mg of etelcalcetide (as hydrochloride) in 0.5 mL of solution. Each mL contains 5 mg etelcalcetide. Parsabiv 5 mg solution for injection Each vial contains 5 mg of etelcalcetide (as hydrochloride) in 1 mL of solution. Each mL contains 5 mg etelcalcetide. Parsabiv 10 mg solution for injection Each vial contains 10 mg of etelcalcetide (as hydrochloride) in 2 mL of solution. Each mL contains 5 mg etelcalcetide. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Solution for injection. Clear colourless solution. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Parsabiv is indicated for the treatment of secondary hyperparathyroidism (SHPT) in adult patients with chronic kidney disease (CKD) on haemodialysis therapy. 4.2 Posology and method of administration Posology The recommended initial dose of etelcalcetide is 5 mg administered by bolus injection 3 times per week. Corrected serum calcium should be at or above the lower limit of the normal range prior to administration of first dose of Parsabiv, a dose increase, or reinitiation after a dose stop (see also dose adjustments based on serum calcium levels). Parsabiv should not be administered more frequently than 3 times per week. Dose titration Parsabiv should be titrated so that doses are individualised between 2.5 mg and 15 mg.
  • Parsabiv® (Etelcalcetide) – Oxford Clinical Policy

    Parsabiv® (Etelcalcetide) – Oxford Clinical Policy

    UnitedHealthcare® Oxford Clinical Policy Parsabiv® (Etelcalcetide) Policy Number: PHARMACY 313.7 T2 Effective Date: April 1, 2021 Instructions for Use Table of Contents Page Related Policies Coverage Rationale ....................................................................... 1 • Drug Coverage Guidelines Prior Authorization Requirements ................................................ 2 Applicable Codes .......................................................................... 2 Background.................................................................................... 2 Clinical Evidence ........................................................................... 2 U.S. Food and Drug Administration ............................................. 3 References ..................................................................................... 3 Policy History/Revision Information ............................................. 3 Instructions for Use ....................................................................... 4 Coverage Rationale Initial Therapy Parsabiv (etelcalcetide) is proven for the treatment of secondary hyperparathyroidism with chronic kidney disease when the following criteria are met: Diagnosis of secondary hyperparathyroidism with chronic kidney disease; and Patient is on dialysis; and Patient is not receiving Parsabiv (etelcalcetide) in combination with Sensipar (cinacalcet hydrochloride); and Prescribed by or in consultation with an endocrinologist or nephrologist; and Dosing is in accordance with the United
  • The Fine Structure of the Parathyroid Gland*

    The Fine Structure of the Parathyroid Gland*

    The Fine Structure of the Parathyroid Gland* BY JERRY STEVEN TRIER, M.D. (From the Department of Anatomy, University of Washington School of Medicine, Seattle) PLATES 3 TO 10 (Received for publication, July 29, 1957) ABSTRACT The fine structure of the parathyroid of the macaque is described, and is cor- related with classical parathyroid cytology as seen in the light microscope. The two parenchymal cell types, the chief cells and the oxyphil cells, have been recognized in electron mierographs. The chief cells contain within their cyto- plasm mitochondria, endoplasmic reticulum, and Golgi bodies similar to those found in other endocrine tissues as well as frequent PAS-positive granules. The juxtanuclear body of the light microscopists is identified with stacks of parallel lamellar elements of the endoplasmic rcticulum of the ergastoplasmic or granular type. Oxyphll cells are characterized by juxtanuclear bodies and by numerous mito- chondria found throughout their cytoplasm. Puzzling lamellar whorls are described in the cytoplasm of some oxyphil cells. The endothelium of parathyroid capillaries is extremely thin in some areas and contains numerous fenestrations as well as an extensive system of vesicles. The possible significance of these structures is discussed. The connective tissue elements found in the perivascular spaces of macaque parathyroid are described. INTRODUCTION Other contributions to the present concepts con cerning the human parathyroid can be found in the It is the purpose of the present paper to report some observations on the fine structure of the reports of Bergstrand (7), Morgan (34), Pappen- parathyroid gland employing the electron micro- heimer and Wilens (45), Castleman and Mallory (10), and Gilmour (20).
  • An Open0label, Single0dose Study to Evaluate the Safety, Tolerability

    An Open0label, Single0dose Study to Evaluate the Safety, Tolerability

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¶V$JUHHPHQW ,KDYHUHDGWKHDWWDFKHGSURWRFROHQWLWOHG$Q2SHQODEHO6LQJOHGRVH6WXG\WR(YDOXDWH WKH6DIHW\7ROHUDELOLW\3KDUPDFRNLQHWLFVDQG3KDUPDFRG\QDPLFVRI(WHOFDOFHWLGH $0* LQ3DHGLDWULF6XEMHFWV$JHGWROHVVWKDQ<HDUVZLWK6HFRQGDU\ +\SHUSDUDWK\URLGLVP V+37 5HFHLYLQJ0DLQWHQDQFH+DHPRGLDO\VLVGDWHG )HEUXDU\DQGDJUHHWRDELGHE\DOOSURYLVLRQVVHWIRUWKWKHUHLQ ,DJUHHWRFRPSO\ZLWKWKH,QWHUQDWLRQDO&RQIHUHQFHRQ+DUPRQLVDWLRQ
  • 2017 Fda Peptide Harvest

    2017 Fda Peptide Harvest

    Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 10 April 2018 doi:10.20944/preprints201804.0126.v1 Peer-reviewed version available at Pharmaceuticals 2018, 11, 42; doi:10.3390/ph11020042 1 Review 2 2017 FDA PEPTIDE HARVEST 3 Othman Al Musaimi,1,2,# Danah Alshaer, 1,2,# Beatriz G. de la Torre,3,* Fernando Albericio,2,4,5.* 4 1 College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa 5 2 School of Chemistry, University of KwaZulu-Natal, Durban 4001, South Africa 6 3 KRISP, College of Health Sciences, University of KwaZulu-Natal, Durban 4001, South Africa 7 4 CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, University of 8 Barcelona, 08028 Barcelona, Spain 9 5 Department of Organic Chemistry, University of Barcelona, 08028 Barcelona, Spain 10 * Correspondence: [email protected]; [email protected]; Tel.: +27-614009144 11 12 13 Abstract: 2017 was an excellent year in terms of new drugs (chemical entities and biologics) 14 approved by the FDA, with a total of forty-six. In turn, one of the highlights was the number of 15 peptides (six) included in this list. Here, the six peptides are analysed in terms of chemical structure, 16 synthetic strategy used for their production, source, biological target, and mode of action. 17 Keywords: pharmaceutical market; drugs; drug discovery; solid-phase peptide synthesis 18 Introduction 19 The financial investment associated with the pharmaceutical industry is one of the largest in the 20 industrial sector—surpassed only by the telecommunications sector. However, the number of new 21 products (drugs) entering the market each year is relatively low.
  • WO 2015/168656 A2 5 November 2015 (05.11.2015) P O P C T

    WO 2015/168656 A2 5 November 2015 (05.11.2015) P O P C T

    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/168656 A2 5 November 2015 (05.11.2015) P O P C T (51) International Patent Classification: (72) Inventors: HSIAO, Sonny; 1985 Pleasant Valley Avenue, A61K 48/00 (2006.01) Apartment 7, Oakland, CA 9461 1 (US). LIU, Cheng; 24 N Hill Court, Oakland, CA 94618 (US). LIU, Hong; 5573 (21) International Application Number: Woodview Drive, El Sobrante, CA 94803 (US). PCT/US20 15/02895 1 (74) Agents: GIERING, Jeffery, C. et al; Wilson Sonsini (22) International Filing Date: Goodrich & Rosati, 650 Page Mill Road, Palo Alto, CA 1 May 2015 (01 .05.2015) 94304-1050 (US). (25) Filing Language: English (81) Designated States (unless otherwise indicated, for every (26) Publication Language: English kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (30) Priority Data: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, 61/988,070 2 May 2014 (02.05.2014) US DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (71) Applicant: ADHEREN INCORPORATED [US/US]; HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, 1026 Rispin Drive, Berkeley, CA 94705 (US). KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (72) Inventors; and PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (71) Applicants : TWITE, Amy, A.
  • Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set

    Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set

    MTC eHealth DSI [eHDSI v2.2.2-OR] eHealth DSI – Master Value Set Catalogue Responsible : eHDSI Solution Provider PublishDate : Wed Nov 08 16:16:10 CET 2017 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 1 of 490 MTC Table of Contents epSOSActiveIngredient 4 epSOSAdministrativeGender 148 epSOSAdverseEventType 149 epSOSAllergenNoDrugs 150 epSOSBloodGroup 155 epSOSBloodPressure 156 epSOSCodeNoMedication 157 epSOSCodeProb 158 epSOSConfidentiality 159 epSOSCountry 160 epSOSDisplayLabel 167 epSOSDocumentCode 170 epSOSDoseForm 171 epSOSHealthcareProfessionalRoles 184 epSOSIllnessesandDisorders 186 epSOSLanguage 448 epSOSMedicalDevices 458 epSOSNullFavor 461 epSOSPackage 462 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 2 of 490 MTC epSOSPersonalRelationship 464 epSOSPregnancyInformation 466 epSOSProcedures 467 epSOSReactionAllergy 470 epSOSResolutionOutcome 472 epSOSRoleClass 473 epSOSRouteofAdministration 474 epSOSSections 477 epSOSSeverity 478 epSOSSocialHistory 479 epSOSStatusCode 480 epSOSSubstitutionCode 481 epSOSTelecomAddress 482 epSOSTimingEvent 483 epSOSUnits 484 epSOSUnknownInformation 487 epSOSVaccine 488 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 3 of 490 MTC epSOSActiveIngredient epSOSActiveIngredient Value Set ID 1.3.6.1.4.1.12559.11.10.1.3.1.42.24 TRANSLATIONS Code System ID Code System Version Concept Code Description (FSN) 2.16.840.1.113883.6.73 2017-01 A ALIMENTARY TRACT AND METABOLISM 2.16.840.1.113883.6.73 2017-01
  • 1 Advances in Therapeutic Peptides Targeting G Protein-Coupled

    1 Advances in Therapeutic Peptides Targeting G Protein-Coupled

    Advances in therapeutic peptides targeting G protein-coupled receptors Anthony P. Davenport1Ϯ Conor C.G. Scully2Ϯ, Chris de Graaf2, Alastair J. H. Brown2 and Janet J. Maguire1 1Experimental Medicine and Immunotherapeutics, Addenbrooke’s Hospital, University of Cambridge, CB2 0QQ, UK 2Sosei Heptares, Granta Park, Cambridge, CB21 6DG, UK. Ϯ Contributed equally Correspondence to Anthony P. Davenport email: [email protected] Abstract Dysregulation of peptide-activated pathways causes a range of diseases, fostering the discovery and clinical development of peptide drugs. Many endogenous peptides activate G protein-coupled receptors (GPCRs) — nearly fifty GPCR peptide drugs have been approved to date, most of them for metabolic disease or oncology, and more than 10 potentially first- in-class peptide therapeutics are in the pipeline. The majority of existing peptide therapeutics are agonists, which reflects the currently dominant strategy of modifying the endogenous peptide sequence of ligands for peptide-binding GPCRs. Increasingly, novel strategies are being employed to develop both agonists and antagonists, and both to introduce chemical novelty and improve drug-like properties. Pharmacodynamic improvements are evolving to bias ligands to activate specific downstream signalling pathways in order to optimise efficacy and reduce side effects. In pharmacokinetics, modifications that increase plasma-half life have been revolutionary. Here, we discuss the current status of peptide drugs targeting GPCRs, with a focus on evolving strategies to improve pharmacokinetic and pharmacodynamic properties. Introduction G protein-coupled receptors (GPCRs) mediate a wide range of signalling processes and are targeted by one third of drugs in clinical use1. Although most GPCR-targeting therapeutics are small molecules2, the endogenous ligands for many GPCRs are peptides (comprising 50 or fewer amino acids), which suggests that this class of molecule could be therapeutically useful.
  • Etelcalcetide

    Etelcalcetide

    Drug and Biologic Coverage Policy Effective Date .......................................... 12/1/2020 Next Review Date… ................................... 12/1/2021 Coverage Policy Number .................................. 1812 Etelcalcetide Table of Contents Related Coverage Resources Coverage Policy .................................................. 1 FDA Approved Indications .................................. 2 Recommended Dosing ....................................... 2 General Background ........................................... 2 Coding/ Billing Information .................................. 3 References .......................................................... 3 INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer’s benefit plan document may contain a specific exclusion
  • Nomenclatore Per L'anatomia Patologica Italiana Arrigo Bondi

    Nomenclatore Per L'anatomia Patologica Italiana Arrigo Bondi

    NAP Nomenclatore per l’Anatomia Patologica Italiana Versione 1.9 Arrigo Bondi Bologna, 2016 NAP v. 1.9, pag 2 Arrigo Bondi * NAP - Nomenclatore per l’Anatomia Patologica Italiana Versione 1.9 * Componente Direttivo Nazionale SIAPEC-IAP Società Italiana di Anatomia Patologica e Citodiagnostica International Academy of Pathology, Italian Division NAP – Depositato presso S.I.A.E. Registrazione n. 2012001925 Distribuito da Palermo, 1 Marzo 2016 NAP v. 1.9, pag 3 Sommario Le novità della versione 1.9 ............................................................................................................... 4 Cosa è cambiato rispetto alla versione 1.8 ........................................................................................... 4 I Nomenclatori della Medicina. ........................................................................................................ 5 ICD, SNOMED ed altri sistemi per la codifica delle diagnosi. ........................................................... 5 Codifica medica ........................................................................................................................... 5 Storia della codifica in medicina .................................................................................................. 5 Lo SNOMED ............................................................................................................................... 6 Un Nomenclatore per l’Anatomia Patologica Italiana ................................................................. 6 Il NAP .................................................................................................................................................