DOCSLIB.ORG

FDA Briefing Document

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
FDA Briefing Document FDA Briefing Document ARTHRITIS ADVISORY COMMITTEE AND DRUG SAFETY AND RISK MANAGEMENT ADVISORY COMMITTEE MEETING January 11, 2019 NDA 21856 Febuxostat Xanthine oxidase (XO) inhibitor for the chronic management of hyperuricemia in patients with gout Takeda 1 of 169 DISCLAIMER STATEMENT The attached package contains background information prepared by the Food and Drug Administration (FDA) for the panel members of the advisory committee. The FDA background package often contains assessments and/or conclusions and recommendations written by individual FDA reviewers. Such conclusions and recommendations do not necessarily represent the final position of the individual reviewers, nor do they necessarily represent the final position of the Review Division or Office. We bring the supplemental new drug application (sNDA) for Uloric (febuxostat) NDA# 21856 which includes the results from the post-marketing safety trial required by FDA to evaluate the cardiovascular (CV) safety of febuxostat - the Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Morbidities (CARES) trial to this Advisory Committee to gain the Committee’s insights and opinions. The background package may not include all issues relevant to the final regulatory recommendation and instead is intended to focus on issues identified by the Agency for discussion by the advisory committee. The FDA will not issue a final determination on the issues at hand until input from the advisory committee process has been considered and all reviews have been finalized. The final determination may be affected by issues not discussed at the advisory committee meeting. 2 of 169 1 Table of Contents 1 Division Memorandum ……………………………………………………………………………….... 6 2 Draft Points to Consider …………………………………………………………………………………. 17 3 Clinical and Statistical Review ………………………………………………………………………….. 18 4 Division of Cardiovascular and Renal Products Consult ……………………………………. 99 5 Office of Surveillance and Epidemiology Review …………………………………………….. 108 6 Office of Surveillance and Epidemiology – Sentinel Memo ……………………………… 138 3 of 169 Table of Tables Table 1 Primary Analysis of MACE – On Study Analysis................................................................ 11 Table 2 Analysis of CV Death and All Cause Death in CARES ........................................................ 12 Table 3: Treatments for the Management of Hyperuricemia ...................................................... 22 Table 4 Summary of Major Safety Results from First Cycle Review of Febuxostat ..................... 26 Table 5: All-Cause Mortality in Febuxostat Safety Database by Patient-Years of Exposure (Data Cut-off 08 February 2006) ............................................................................................................. 27 Table 6: Clinical Trials Relevant to this NDA ................................................................................. 31 Table 7 – Tabular Summary of Major Inclusion and Exclusion Criteria for Study 301 ................. 35 Table 8 - Tabular Summary of Assessments and Procedures for Study 301 ................................ 38 Table 9: Cardiovascular Endpoint Definitions Used to Adjudicate Deaths Reported in Study 301 .... 40 Table 10. Subjects Follow-up Until Trial Discontinuation (FAS) ................................................... 48 Table 11. Exposure Time in Subjects Exposed to Study Treatment (FAS) .................................... 49 Table 12. Disposition of Subjects by Vital Status .......................................................................... 50 Table 13 Follow-up Time and Treatment Exposure in Subjects Who Prematurely Discontinued Study Treatment ........................................................................................................................... 50 Table 14 Follow-up Time and Treatment Exposure in Subjects Who Prematurely Discontinued Study Visits .................................................................................................................................... 51 Table 15: Summary of Protocol Violations/Deviations for Study 301 .......................................... 51 Table 16: Baseline Demographics of Subjects Enrolled in Study 301 ........................................... 52 Table 17: Comorbid Disease Risk Factors for Subjects Enrolled in Study 301 .............................. 53 Table 18: Summary of Subjects' Gout History, Disease Status and Treatment History for Study 301 ................................................................................................................................................ 54 Table 19: Summary of Subjects' Cardiovascular History in Study 301 ......................................... 55 Table 20: Subjects' Compliance with Randomized Study Medication for Study 301 .................. 56 Table 21: Summary of Study Drug Dose Adjustments for Study 301 (All Subjects) ..................... 57 Table 22: Prophylactic Gout Medication Use and Dose Adjustments for Study 301 ................... 57 Table 23: Concomitant Medications Taken by > 10% of Subjects in Study 301 ........................... 58 Table 24 Primary Analysis of MACE – Number of Events ............................................................ 60 Table 25. Secondary Analysis of Cardiovascular Endpoints – Number of Events ......................... 62 Table 26. Number Needed to Harm in Study TMX-301 ................................................................ 63 Table 27. Number of Event by the Windows of Time after Treatment Discontinuation ............. 64 Table 28. Analysis of CV Death and All-Cause Death – Number of Events ................................... 65 Table 29. Sensitivity Analysis by Renal Function Status and Final Dose of Treatment Drug ........ 66 Table 30. Additional 199 deaths by Windows of Time after Treatment Discontinuation............ 67 Table 31. Follow-up Time and Treatment Exposure Time for Additional 199 Deaths ................. 68 Table 32. Follow-up Time in 821 Subjects with Unknown Vital Status ........................................ 68 Table 33. Primary and Secondary Analyses of Cardiovascular Endpoints .................................... 72 Table 34: Summary of Subjects by Treatment Group Who Experienced Treatment Emergent Adverse Events and Deaths During Study 301.............................................................................. 74 Table 35: Treatment Emergent Adverse Events Leading to Death by MedDRA System Organ Class and Preferred Term by Treatment Group for Study 301 ..................................................... 75 4 of 169 Table 36: Causes of Adjudicated Cardiovascular Deaths Reported in Study 301 by Various Time Windows ....................................................................................................................................... 79 Table 37: Summary of Adjudicated Non-Cardiovascular Deaths by MedDRA Preferred Term by Treatment Group for Study 301 ................................................................................................... 80 Table 38: Abridged Summary of Treatment-Emergent Serious Adverse Events (SAEs) by MedDRA System Organ Class and Preferred Term Occurring in >1% of Subjects by Randomized Treatment Group for Study 301 ................................................................................................... 81 Table 39: Treatment Emergent Adverse Events Leading to Discontinuation of Randomized Study Medication by MedDRA System Organ Class/Preferred Term Occurring in > 0.1% of Subjects by Randomized Treatment Group for Study 301 .............................................................................. 85 Table 40: Summary of Severe Treatment Emergent Adverse Events (TEAEs)1 by MedDRA System Organ Class in Study 3012 ............................................................................................................. 87 Table 41: Treatment Emergent Adverse Events1 (TEAEs) by MedDRA System Organ Class by Treatment Group for Study 3012 .................................................................................................. 88 Table 42: Summary of Common Treatment Emergent Adverse Events1 by Preferred Term Occurring in >5% of Subjects by Treatment Group in Study 3012,3 .............................................. 89 Table 43: Proportion of Subjects with Serum Uric Acid Levels <6.0 mg/dL and <5.0 mg/dL by Visit by Treatment Group in Study 301 (Full Analysis Set) ........................................................... 90 Table 44: Proportion of Subjects with Gout Flares Requiring Treatment During Study 301 (Full Analysis Set) .................................................................................................................................. 91 Table of Figures Figure 1 Schema of Study 301 ...................................................................................................... 35 Figure 2.Disposition of Subjects in Trial TMX-301 ........................................................................ 47 Figure 3. Discontinuations from Study Visits ................................................................................ 48 Figure 4. Study Follow-up Until Trial Discontinuation .................................................................. 49 Figure 5. Kaplan-Meier Cumulative Probability of Primary MACE by Treatment ........................ 60 Figure 6. Kaplan-Meier Plot for Cardiovascular Death ................................................................. 61 Figure 7. Kaplan-Meier
Load more

Recommended publications
  • Zurampic (Lesinurad)
    Market Applicability Market DC GA KY MD NJ NY WA Applicable X X X X X X NA Zurampic (lesinurad) Override(s) Approval Duration Prior Authorization 1 year Quantity Limit Medications Quantity Limit Zurampic (lesinurad) May be subject to quantity limit APPROVAL CRITERIA Requests for Zurampic (lesinurad) may be approved if the following criteria are met: I. Individual has had a previous trial (medication samples/coupons/discount cards are excluded from consideration as a trial) and inadequate response (unable to achieve target serum uric acid levels) to one preferred xanthine oxidase inhibitor (allopurinol, febuxostat*); AND II. Individual has hyperuricemia associated with gout; AND III. Individual is unable to achieve target serum uric acid levels while on a xanthine oxidase inhibitor (such as allopurinol or febuxostat*); AND IV. Individual remains symptomatic (such as, but not limited to joint pain, swelling, limited range of motion, erythema) despite use of xanthine oxidase inhibitor; AND V. Individual will continue use of a xanthine oxidase inhibitor in conjunction with Zurampic. *requires prior authorization Zurampic (lesinurad) may not be approved for the following: I. Individual has severe renal impairment (creatinine clearance less than 30 mL/min), end stage renal disease, is on dialysis or is a kidney transplant recipient; OR II. Individual has Lesch-Nyhan syndrome or tumor lysis syndrome. PAGE 1 of 2 08/14/2019 This policy does not apply to health plans or member categories that do not have pharmacy benefits, nor does it apply to Medicare. Note that market specific restrictions or transition-of-care benefit limitations may apply. CRX-ALL-0429-19 Market Applicability Market DC GA KY MD NJ NY WA Applicable X X X X X X NA Note: Zurampic (lesinurad) has a black box warning indicating risk of acute renal failure is more common when Zurampic is used without a xanthine oxidase inhibitor.
    [Show full text]
  • Pegloticase: a New Biologic for Treating Advanced Gout
    Drug Evaluation Pegloticase: a new biologic for treating advanced gout Although pharmacologic therapies for hyperuricemia in patients with gout have been well established and are reasonably effective, a small proportion of patients are refractory to treatment and/or present with articular disease so severe as to render standard treatments inadequate. Pegloticase, a PEGylated mammalian urate oxidase with a novel mechanism of action, was recently approved in the USA for the treatment of chronic gout in adult patients refractory to conventional therapy. This paper outlines the development of this unique agent and provides details of the Phase III clinical trial program. A discussion of patient selection, treatment considerations, and risk management for infused pegloticase follows. As a new class of biologic agent offering documented and dramatic effects on lowering serum uric acid and remarkably rapid outcomes in resolving tophi, pegloticase can provide safe and effective management of hyperuricemia and gout for many patients, particularly those who have a high disease burden or who have previously failed to respond to other therapies. KEYWORDS: biologic therapy n chronic gout n hyperuricemia n pegloticase Herbert SB Baraf* & Alan K Matsumoto Among the rheumatic diseases, few are as well have disease that is refractory to current thera- George Washington University, understood as gout. The cause of gout, prolonged pies. These patients often have a chronic, symp- Center for Rheumatology & Bone Research, a Division of Arthritis & hyperuricemia resulting from excess production tomatic, destructive arthropathy, frequent acute Rheumatism Associates, 2730 or decreased excretion of uric acid (UA), was first flares of joint pain and disfiguring tophaceous University Blvd West, Wheaton, MD 20902, USA described by Garrod in the mid-19th century [1].
    [Show full text]
  • Sulfinpyrazone 100Mg and 200Mg Tablets (Sulfinpyrazone)
    Prescribing information sulfinpyrazone 100mg and 200mg tablets (sulfinpyrazone) Presentation: Coated tablets agents, sulphonamides, penicillin, theophylline, phenytoin, non- indication: Chronic, including tophaceous gout; recurrent gouty steroidal antirheumatic drugs. arthritis; hyperuricaemia Pregnancy and lactation: Used with caution in pregnant women, Dosage and administration: Route of administration: Oral. Adults: weighing the potential risk against the possible benefits. It is not known 100-200mg daily increasing gradually (over the first two or three whether the active substance or its metabolite(s) pass into breast milk. weeks) to 600mg daily (rarely 800mg), and maintained until the For safety reasons mothers should refrain from taking the drug. serum urate level has fallen within the normal range. Maintenance Undesirable effects: Mild transient gastro-intestinal upsets, such dose may be as low as 200mg daily. Children: Paediatric usage as nausea, vomiting, diarrhea, gastro-intestinal bleeding and not established. ulcers, acute renal failure, salt and water retention, allergic skin contraindications: Acute attacks of gout. Gastric and duodenal reactions, leucopenia, thrombocytopenia, agranulocytosis, aplastic ulcer. Known hypersensitivity to sulfinpyrazone and other pyrazolone anaemia, hepatic dysfunction, jaundice and hepatitis. derivatives. Contra-indicated in patients with asthma, urticaria, or (Please refer to the Summary of Product Characteristics for acute rhinitis, severe parenchymal lesions of the liver or kidneys, detailed information) porphyria, blood dyscrasias, haemorrhagic diatheses overdose: Nausea, vomiting, abdominal pains, diarrhoea, Precautions and warnings: Used with caution in patients with hypotension, cardiac arrhythmias, hyperventilation, respiratory hyperuricaemia or gout, episodes of urolithiasis or renal colic, disorders, impairment of consciousness, coma, epileptic seizures, ensure adequate fluid intake and alkalinisation of the urine during oliguria or anuria, acute renal failure, renal colic.
    [Show full text]
  • New Therapeutic Agents Marketed in 2015: Part 4 Amy M
    CPE New therapeutic agents marketed in 2015: Part 4 Amy M. Lugo and Brian Park Amy M. Lugo, PharmD, BCPS, BC-ADM, Abstract FAPhA, Clinical Pharmacy Specialist, Pharmacy Operations Division, Formu- lary Management Branch, Defense Health Objective: To provide information about the most important properties of new Agency, San Antonio therapeutic agents approved by FDA and first marketed in 2015. Brian Park, PharmD candidate, University of Data sources: Product labeling supplemented selectively with published stud- New England College of Pharmacy, Portland, ies and drug information reference sources. ME Data synthesis: This review covers 11 new therapeutic agents approved by FDA Correspondence: Amy M. Lugo, 7800 and first marketed in the United States in 2015: selexipag, cobimetinib, osimertinib, IH-10 W, Ste. 335, San Antonio, TX 78230; necitumumab, alectinib, insulin degludec, lesinurad, mepolizumab, brexpiprazole, [email protected] cariprazine, and flibanserin. Indications and information on dosage and adminis- Disclosure: The authors declare no conflicts tration for these agents are reviewed, as well as efficacy, safety, the most important of interest or financial interests in any product or service mentioned in this article. pharmacokinetic properties, drug interactions, and other precautions. Practical considerations for use of these new agents also are discussed. Whenever possible, Department of Defense (DoD) disclaimer: The information discussed here represents properties of the new drugs are compared with those of older agents marketed for the views of the author and does not neces- the same indications. sarily reflect the views of DoD or the Depart- Summary: Selexipag is the second oral prostacyclin agonist for the treatment ments of the Army, Navy, or Air Force.
    [Show full text]
  • New Zealand Data Sheet
    NEW ZEALAND DATA SHEET 1 PRODUCT NAME DICLOFENAC SANDOZ 25mg enteric coated tablet 50mg enteric coated tablet 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Each Diclofenac Sandoz 25 mg tablet contains Diclofenac Sodium 25mg Each Diclofenac Sandoz 50 mg tablet contains Diclofenac Sodium 50mg Tablets contain lactose. For the full list of excipients, see section 6.1. 3 PHARMACEUTICAL FORM 25 mg Brown-yellow gastro-resistant film coated tablets, round, biconvex faced with a plain rim. Approximate tablet dimensions: diameter 6.1 to 6.3 mm; thickness 2.9 to 3.2 mm. Each tablet contains Diclofenac Sodium Ph Eur 25 mg. 50 mg Brown-yellow gastro-resistant film coated tablets, round, biconvex faced with a banded rim. Approximate tablet dimensions: diameter 8.0 to 8.3 mm; thickness 3.5 to 3.8 mm. Each tablet contains Diclofenac Sodium Ph Eur 50 mg. 4 CLINICAL PARTICULARS 4.1 Therapeutic indications Treatment of: • Inflammatory and degenerative forms of rheumatism - rheumatoid arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis, osteoarthritis and spondylarthritis, painful syndromes of the vertebral column, non-articular rheumatism; • Acute attacks of gout; • Post-traumatic and post-operative pain, inflammation, and swelling, e.g. following dental or orthopaedic surgery; • Painful and/or inflammatory conditions in gynaecology, e.g. primary dysmenorrhoea or adnexitis; • As an adjuvant in severe painful inflammatory infections of the ear, nose, or throat, e.g. pharyngotonsillitis, otitis. In keeping with general therapeutic principles, the underlying Page 1 of 18 NEW ZEALAND DATA SHEET disease should be treated with basic therapy, as appropriate. Fever alone is not an indication. 4.2 Dose and method of administration Dosage Diclofenac Sandoz should only be prescribed when the benefits are considered to outweigh the potential risks.
    [Show full text]
  • Stems for Nonproprietary Drug Names
    USAN STEM LIST STEM DEFINITION EXAMPLES -abine (see -arabine, -citabine) -ac anti-inflammatory agents (acetic acid derivatives) bromfenac dexpemedolac -acetam (see -racetam) -adol or analgesics (mixed opiate receptor agonists/ tazadolene -adol- antagonists) spiradolene levonantradol -adox antibacterials (quinoline dioxide derivatives) carbadox -afenone antiarrhythmics (propafenone derivatives) alprafenone diprafenonex -afil PDE5 inhibitors tadalafil -aj- antiarrhythmics (ajmaline derivatives) lorajmine -aldrate antacid aluminum salts magaldrate -algron alpha1 - and alpha2 - adrenoreceptor agonists dabuzalgron -alol combined alpha and beta blockers labetalol medroxalol -amidis antimyloidotics tafamidis -amivir (see -vir) -ampa ionotropic non-NMDA glutamate receptors (AMPA and/or KA receptors) subgroup: -ampanel antagonists becampanel -ampator modulators forampator -anib angiogenesis inhibitors pegaptanib cediranib 1 subgroup: -siranib siRNA bevasiranib -andr- androgens nandrolone -anserin serotonin 5-HT2 receptor antagonists altanserin tropanserin adatanserin -antel anthelmintics (undefined group) carbantel subgroup: -quantel 2-deoxoparaherquamide A derivatives derquantel -antrone antineoplastics; anthraquinone derivatives pixantrone -apsel P-selectin antagonists torapsel -arabine antineoplastics (arabinofuranosyl derivatives) fazarabine fludarabine aril-, -aril, -aril- antiviral (arildone derivatives) pleconaril arildone fosarilate -arit antirheumatics (lobenzarit type) lobenzarit clobuzarit -arol anticoagulants (dicumarol type) dicumarol
    [Show full text]
  • PM179 Pegloticase (Krystexxa)
    Original Department: Pharmacy Management 03/23/2021 Approval: Policy #: PM179 Last Approval: 03/23/2021 Title: Pegloticase (Krystexxa) Approved By: UM Committee Line(s) of Business WAH-IMC (HCA) BHSO Medicare Advantage (CMS) Medicare SNP (CMS) Cascade Select Documentation required to determine medical necessity for Pegloticase (Krystexxa): History and/or physical examination notes and relevant specialty consultation notes that address the problem and need for the service: Diagnosis-Age-Medication list (current and past)- Labs/Diagnostics. BACKGROUND Krystexxa is a PEGylated uric acid specific enzyme indicated for treatment of chronic gout in adult patients refractory to conventional therapy.1-2 It is made up of a recombinant modified mammalian uricase produced by a genetically modified strain of Escherichia coli which is covalently bonded to monomethoxypoly (ethylene glycol) [mPEG].1 The recommended dose of Krystexxa is 8 mg administered every 2 weeks over no less than 120 minutes as an intravenous (IV) infusion. Before beginning therapy with Krystexxa, it is recommended that all oral urate-lowering therapies (ULTs) are discontinued and not restarted while on Krystexxa because concomitant use may blunt any increase in serum uric acid (SUA) levels. It is recommended to monitor SUA prior to infusions and consider discontinuing treatment if levels increase to above 6 mg/dL.1 Disease Overview Gout results from a metabolic disorder called hyperuricemia caused by an overproduction or underexcretion of uric acid. Hyperuricemia is typically defined as a serum uric acid level greater than 6.8 mg/dL; however, asymptomatic patients with elevated uric acid levels do not have gout and do not require treatment.3-4 Excessive amounts of uric acid in the blood lead to deposits of crystals in the joints and connective tissues and may cause excruciating pain.
    [Show full text]
  • Guidelines for Management of Gout. Part 1: Systematic Nonpharmacologic and Pharmacologic Therapeutic Approaches to Hyperuricemia DINESH KHANNA,1 JOHN D
    Arthritis Care & Research Vol. 64, No. 10, October 2012, pp 1431–1446 DOI 10.1002/acr.21772 © 2012, American College of Rheumatology SPECIAL ARTICLE 2012 American College of Rheumatology Guidelines for Management of Gout. Part 1: Systematic Nonpharmacologic and Pharmacologic Therapeutic Approaches to Hyperuricemia DINESH KHANNA,1 JOHN D. FITZGERALD,2 PUJA P. KHANNA,1 SANGMEE BAE,2 MANJIT K. SINGH,3 TUHINA NEOGI,4 MICHAEL H. PILLINGER,5 JOAN MERILL,6 SUSAN LEE,7 SHRADDHA PRAKASH,2 MARIAN KALDAS,2 MANEESH GOGIA,2 FERNANDO PEREZ-RUIZ,8 WILL TAYLOR,9 FRE´ DE´ RIC LIOTE´ ,10 HYON CHOI,4 JASVINDER A. SINGH,11 NICOLA DALBETH,12 SANFORD KAPLAN,13 VANDANA NIYYAR,14 DANIELLE JONES,14 STEVEN A. YAROWS,15 BLAKE ROESSLER,1 GAIL KERR,16 CHARLES KING,17 GERALD LEVY,18 DANIEL E. FURST,2 N. LAWRENCE EDWARDS,19 BRIAN MANDELL,20 H. RALPH SCHUMACHER,21 MARK ROBBINS,22 2 7 NEIL WENGER, AND ROBERT TERKELTAUB Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient. The ACR considers adherence to these guidelines and recommendations to be voluntary, with the ultimate determi- nation regarding their application to be made by the physician in light of each patient’s individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed or endorsed by the ACR are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice.
    [Show full text]
  • Nonsteroidal Antiinflammatory Drugs and Acute Renal Failure in Elderly Persons
    American Journal of Epidemiology Vol. 151, No. 5 Copyright © 2000 by The Johns Hopkins University School of Hygiene and Public Health Printed In U.S.A. Ail rights reserved Nonsteroidal Antiinflammatory Drugs and Acute Renal Failure in Elderly Persons Marie R. Griffin,1'2 Aida Yared,3 and Wayne A. Ray1 Renal prostaglandin inhibition by nonsteroidal antiinflammatory drugs (NSAIDs) may decrease renal function, Downloaded from https://academic.oup.com/aje/article/151/5/488/117194 by guest on 27 September 2021 especially under conditions of low effective circulating volume. To evaluate the risk of important deterioration of renal function due to this effect, the authors performed a nested case-control study using Tennessee Medicaid enrollees aged £65 years in 1987-1991. Cases were patients who had been hospitalized with community- acquired acute renal failure; they were selected on the basis of medical record review of Medicaid enrollees with selected discharge diagnoses. Information on the timing, duration, and dose of prescription NSAIDs used, demographic factors, and comorbidity was gathered from computerized Medicaid-Medicare data files. Of the 1,799 patients with acute renal failure (4.51 hospitalizations per 1,000 person-years), 18.1% were current users of prescription NSAIDs as compared with 11.3% of 9,899 randomly selected population controls. After control for demographic factors and comorbidity, use of NSAIDs increased the risk of acute renal failure 58% (adjusted odds ratio = 1.58; 95% confidence interval (Cl): 1.34, 1.86). For ibuprofen, which accounted for 35% of NSAID use, odds ratios associated with dosages of £1,200 mg/day, >1,200-<2,400 mg/day, and £2,400 mg/day were 0.94 (95% Cl: 0.58, 1.51), 1.89 (95% Cl: 1.34, 2.67), and 2.32 (95% Cl: 1.45, 3.71), respectively (test for linear trend: p = 0.009).
    [Show full text]
  • WO 2010/099522 Al
    (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 2 September 2010 (02.09.2010) WO 2010/099522 Al (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 45/06 (2006.01) A61K 31/4164 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 31/4045 (2006.01) A61K 31/00 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) International Application Number: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/US2010/025725 HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 1 March 2010 (01 .03.2010) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, (25) Filing Language: English SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, (26) Publication Language: English TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 61/156,129 27 February 2009 (27.02.2009) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, (71) Applicant (for all designated States except US): ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, HELSINN THERAPEUTICS (U.S.), INC.
    [Show full text]
  • Pegloticase - Drugbank
    8/14/2018 Pegloticase - DrugBank Pegloticase Targets (1) Biointeractions (1) IDENTIFICATION Name Pegloticase Accession Number DB09208 Type Biotech Groups Approved, Investigational Biologic Classification Protein Based Therapies Recombinant Enzymes Description Pegloticase is a recombinant procine-like uricase drug indicated for the treatment of severe, treatment-refractory, chronic gout. Similarly to rasburicase, pegloticase metabolises the conversion of uric acid to allantoin. This reduces the risk of precipitate formation and development of gout, since allantoin is five to ten times more soluble than uric acid. In contrast to rasburicase, pegloticase is pegylated to increase its elimination half-life from about eight hours to ten or twelve days, and to decrease the immunogenicity of the foreign uricase protein. This modification allows for an application just once every two to four weeks, making this drug suitable for long-term treatment. Protein chemical formula C1549H2430N408O448S8 Protein average weight 34192.8533 Da Sequences > Pegloticase TYKKNDEVEFVRTGYGKDMIKVLHIQRDGKYHSIKEVATTVQLTLSSKKDYLHGDNSDVI PTDTIKNTVNVLAKFKGIKSIETFAVTICEHFLSSFKHVIRAQVYVEEVPWKRFEKNGVK HVHAFIYTPTGTHFCEVEQIRNGPPVIHSGIKDLKVLKTTQSGFEGFIKDQFTTLPEVKD RCFATQVYCKWRYHQGRDVDFEATWDTVRSIVLQKFAGPYDKGEYSPSVQKTLYDIQVLT LGQVPEIEDMEISLPNIHYLNIDMSKMGLINKEEVLLPLDNPYGKITGTVKRKLSSRL https://www.drugbank.ca/drugs/DB09208 1/9 8/14/2018 Pegloticase - DrugBank Download FASTA Format Synonyms Puricase Prescription Products Search MARKETING MARKETING NAME ↑↓ DOSAGE ↑↓ STRENGTH ↑↓ ROUTE
    [Show full text]
  • Krystexxa® (Pegloticase)
    Krystexxa® (pegloticase) (Intravenous) Document Number: IC-0158 Last Review Date: 10/01/2020 Date of Origin: 02/07/20103 Dates Reviewed: 11/2013, 08/2014, 07/2015, 07/2016, 09/2016, 12/2016, 03/2017, 06/2017, 09/2017, 12/2017, 03/2018, 06/2018, 10/2018, 10/2019, 10/2020 I. Length of Authorization Coverage is provided for six months and will be eligible for renewal. II. Dosing Limits A. Quantity Limit (max daily dose) [NDC Unit]: • Krystexxa 8 mg/mL single-use vial: 2 vials every 28 days B. Max Units (per dose and over time) [HCPCS Unit]: • 16 billable units every 28 days 1 III. Initial Approval Criteria Coverage is provided in the following conditions: • Patient is at least 18 years of age; AND • Patients at higher risk for glucose-6-phosphate dehydrogenase (G6PD) deficiency should be screened and found negative for G6PD before starting Krystexxa; AND • Documentation of baseline serum uric acid level > 8 mg/dL (current lab reports are required for renewal); AND Universal Criteria 1,2 • Therapy will not be given in combination with other urate lowering therapies such as allopurinol, febuxostat, probenecid, lesinurad, etc.; AND Chronic Gout † Ф 1 • Documented contraindication, intolerance, or clinical failure (i.e., inability to reduce serum uric acid to < 6 mg/dL) during a minimum (3) month trial on previous therapy with maximum tolerated dose of xanthine oxidase inhibitors (e.g., allopurinol or febuxostat) or uricosuric agents (e.g., probenecid, lenisurad, etc.); AND • Patient has one of the following: Proprietary & Confidential © 2020 Magellan Health, Inc. o 2 or more gout flares per year that were inadequately controlled by colchicine, nonsteroidal anti-inflammatory drugs (NSAIDS), or oral or injectable corticosteroids; OR o Nonresolving subcutaneous tophi † FDA-labeled indication(s); Ф Orphan Drug 1 IV.
    [Show full text]