DOCSLIB.ORG

“Beyond Anti-VEGF-A for Retinal Diseases”

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
“Beyond Anti-VEGF-A for Retinal Diseases” “Beyond anti-VEGF-A for Retinal Diseases” New York City, KOL Forum, November 6 2018 Megan Baldwin PhD, CEO & Managing Director NEOVASCULAR AMD CURRENT TREATMENT PARADIGMS AND UNMET NEEDS ARSHAD M. KHANANI MD,MA MANAGING PARTNER, DIRECTOR OF CLINICAL RESEARCH, DIRECTOR OF FEL LOWSHIP SIERRA EYE ASSOCIATES CLINICAL ASSOCIATE PROFESSOR UNIVERSITY OF NEVADA - RENO OBJECTIVES ▪ PRACTICE SETTING ▪ STANDARD OF CARE DOSING STRATEGIES ▪ CLINICAL TRIALS DATA HIGHLIGHTING UNMET NEEDS ▪ NEW TREATMENTS ON THE HORIZON PRACTICE SETTING ▪ PRIVATE OFFICE BASED PRACTICE ▪ MULTISPECIALTY WITH 2 RETINAL PHYSICIANS ▪ 55 EMPLOYEES TOTAL ▪ 7 TECHNICIANS, 3 RESEARCH COORDINATORS ▪ 15-20 ACTIVE CLINICAL TRIALS ▪ 70 PATIENTS A DAY ON AVERAGE ▪ APPROXIMATELY 500 INJECTIONS A MONTH ANGIOGENESIS IN AGE-RELATED MACULAR DEGENERATION COMPLEX CASCADE OF EVENTS VEGF Vascular Endothelial Growth Factor Tube formation + remodeling Endothelial cell activation Basement membrane degradation Endothelial cell proliferation, migration Griffioen AW, et al. Pharmacol Rev. 2000;52(2):237-68; Das A, et al. Prog Retin Eye Res. 2003;22(6):721-48; Davis GE, et al. Circ Res. 2005;97(11):1093-107. CURRENT PARADIGM – BLOCK VEGF-A VEGF Vascular Endothelial Growth Factor Tube formation + remodeling Endothelial cell activation Basement membrane Endothelial cell proliferation, degradation migration Griffioen AW, et al. Pharmacol Rev. 2000;52(2):237-68; Das A, et al. Prog Retin Eye Res. 2003;22(6):721-48; Davis GE, et al. Circ Res. 2005;97(11):1093-107. CURRENT ANTI-VEGF-A THERAPIES FOR nAMD ▪ ANTI-VEGF-A THERAPY HAS REVOLUTIONIZED THE MANAGEMENT OF nAMD IN THE PAST 10-15 YEARS ▪ THREE MOLECULES CURRENTLY USED: ▪ RANIBIZUMAB (LUCENTIS) ▪ BEVACIZUMAB (AVASTIN) ▪ AFLIBERCEPT (EYLEA) ANTI-VEGF-A DOSING STRATEGIES USED IN CLINICAL TRIALS TO OPTIMIZE OUTCOMES AND MANAGE nAMD DISEASE MONTHLY - ANCHOR - MARINA - CATT - HARBOR PRN TREAT AND - SAILOR EXTEND - CATT - LUCAS - HARBOR - TREX - ALTAIR CONTINUOUS FIXED MONTHLY DOSING: VISUAL ACUITY FROM BASELINE THROUGH MONTH 24 MARINA1 MONTHS MONTHS ANCHOR2 VIEW 1 and 23 1. Rosenfeld PJ et al. N Engl J Med. 2006;355:1419-1431. 2. Brown DM et al. N Engl J Med. 2006;355:1432-1444. 3. Heier JS et al. Ophthalmology. 2012;119:2537-2548. CONTINUOUS MONTHLY DOSING WHY DO IT? ▪ EVIDENCE OF IMPROVING VISION ▪ MAINTAIN VISION AND RETINAL DRYING ▪ AVOIDS UNDER-TREATMENT WHY NOT DO IT? ▪ NOT INDIVIDUALIZED ▪ nAMD IS HETEROGENEOUS ▪ VARIABLE NATURAL HISTORY AND TREATMENT RESPONSE ▪ MANY PATIENTS DO WELL WITHOUT MONTHLY TREATMENT ▪ VEGF-A SUPPRESSION VARIES BETWEEN PATIENTS ▪ RESULTS BEYOND 2 YEARS LARGELY UNKNOWN CONSEQUENCES OF OVERTREATMENT ▪ EXPENSE: DIRECT AND INDIRECT COSTS ▪ INCONVENIENCE: FREQUENT VISITS ▪ INCREASED RISK (CUMULATIVE) ▪ INFECTION ▪ SUSTAINED IOP ELEVATION/GLAUCOMA INDIVIDUALIZED ANTI-VEGF TREATMENT WHY? HOW? GOALS AVOID OVERTREATMENT SUPPRESS CNV PRN (AS NEEDED) GROWTH, EXUDATION SAFER FREQUENT OCT MORE TREAT-AND-EXTEND IMAGING WITH “ZERO TOLERANCE” COST-EFFECTIVE PRN DOSING IN HARBOR DISTRIBUTION OF THE NUMBER OF RANIBIZUMAB INJECTIONS OVER 2 YEARS Ho AC, Busbee BG, Regillo CD, et al. Ophthalmology. 2014;121(11):2181-2192. UNDERTREATMENT COMPROMISES VISUAL ACUITY POSITIVE CORRELATION OF VA GAINS AND NUMBER OF MANY PATIENTS RECEIVE FEWER INJECTIONS ANTI-VEGF-A INJECTIONS OVER 12 MONTHS IN REAL-WORLD VS CLINICAL STUDIES US medical claims database: Patients received a mean of only 4.6 and 6.9 injections of bevacizumab & ranibizumab over 12 mo, respectively Hussain RM et al. Ophthalmic Surg Lasers Imaging Retina. 2017;48:780-784. PRO RE NATA (PRN) DOSING PATIENTS RECEIVE: ▪ A SERIES OF MONTHLY LOADING INJECTIONS OF ANTI -VEGF THERAPY ▪ REGULAR OFFICE VISITS FOR ASSESSMENT OF VISUAL ACUITY ▪ ANATOMIC MEASURES BASED ON OCT, FA OR OTHER IMAGING MODALITIES POTENTIAL LIMITATIONS OF DISCONTINUOUS PRN ▪ ALLOWS FOR RECURRENCE OF NEOVASCULAR LEAKAGE AND GROWTH ▪ MULTIPLE RECURRENCES LEADS TO PROGRESSION OF DISEASE ▪ POORER LONG-TERM VISUAL OUTCOMES IN SOME PATIENTS Wai KM et al. Am J Ophthalmic Clin Trials. 2018;1:1. TREAT-AND-EXTEND DOSING: WHAT IS IT? ▪ SERIES OF LOADING ANTI-VEGF INJECTIONS, (TYPICALLY 4-WK INTERVALS), WITH VA AND ANATOMIC ASSESSMENT ▪ WHEN CRITERIA INDICATING NO DISEASE ACTIVITY ARE MET, PATIENTS RECEIVE AN INJECTION; TREATMENT INTERVAL IS EXTENDED, USUALLY BY 2 WEEKS AT A TIME, UNTIL MAXIMUM INTERVAL OF 12 –16 WEEKS IS REACHED ▪ IF CNV LESIONS ARE REACTIVATED, TREATMENT INTERVAL IS REDUCED Spaide R. Am J Ophthalmol. 2007;144:679-680 BENEFITS OF TREAT-AND-EXTEND DOSING ▪ CONTINUOUS (PROACTIVE) ▪ MINIMIZES RECURRENCES/SETBACKS ▪ VARIABLE (INDIVIDUALIZED) ▪ MINIMIZES OVERTREATMENT ▪ MINIMIZES TREATMENT BURDEN ▪ MAXIMIZES SAFETY ▪ COST-EFFECTIVE ▪ MINIMIZES DRUG USE, TESTING, AND OFFICE Spaide R. Am J Ophthalmol. 2007;144:679-680 CURRENT UNMET NEEDS IN nAMD NEOVASCULAR AMD ANTI-VEGF A BLOCKADE 15 10 20/63 5 0 20/100 0 6 12 18 24 +25 -5 -10 Mean Changei in ETDRS BCVA ETDRS in Changei Mean -15 -20 Months ANCHOR, MARINA, HARBOR, CATT, VIEW1/2 Brown DM, et al. Ophthalmology. 2009 Jan;116(1):57-65.e5; Rosenfeld PJ, et al; N Engl J Med. 2006;355:1419-1431; Ho AC, et al. Ophthalmology. 2014 Nov;121(11):2181-92; Martin DF, et al. Ophthalmology. 2012; 119(7):1388-98; Heier JS, et al. Ophthalmology. 2012 Dec;119(12):2537-48 NEOVASCULAR AMD – SHORTCOMINGS OF VEGF-A BLOCKADE 20/20 35 >70% VA REMAINS TO BE GAINED 25 15 20/100 5 0 6 12 18 24 -5 Mean Changei in ETDRS BCVA ETDRS in Changei Mean -15 #1 EFFICACY -25 MONTHS Brown DM, et al. Ophthalmology. 2009 Jan;116(1):57-65.e5; Rosenfeld PJ, et al; N Engl J Med. 2006;355:1419-1431; Ho AC, et al. Ophthalmology. 2014 Nov;121(11):2181-92; Martin DF, et al. Ophthalmology. 2012; 119(7):1388-98; Heier JS, et al. Ophthalmology. 2012 Dec;119(12):2537-48 20/200 20/200 #2 Durability X 8 20/40 ANTI-VEGF-A TREATMENT OF nAMD - PROSPECTIVE FIXED OR PRN DOSING ANCHOR, MARINA, HARBOR, CATT, VIEW1/2 Injections 15 Mean = 10.2 Range = 6.6-12.3 11.3 MARINA 0.5 mg 10 ANCHOR (0.5 mg) HARBOR 0.5 mg Monthly Mean = 8.4 CATT Ranibizumab Monthly HARBOR 0.5 mg PRN 5 5.9 CATT Bevacizumab Monthly CATT Ranibizumab PRN Mean Change in ETDRS BCVA ETDRS in Change Mean CATT Bevacizumab PRN VIEW1 (0.5q4) VIEW1 (2q8) 0 VIEW1 (2q4) 0 3 6 9 12 VIEW2 (0.5q4) Months VIEW2 (2q8) Brown DM, et al. Ophthalmology. 2009 Jan;116(1):57-65.e5; Rosenfeld PJ, et al; N Engl J Med. 2006;355:1419-1431; Ho AC, et al. Ophthalmology. 2014 Nov;121(11):2181-92; Martin DF, et al. VIEW2 (2q4) Ophthalmology. 2012; 119(7):1388-98; Heier JS, et al. Ophthalmology. 2012 Dec;119(12):2537-48 ANTI-VEGF-A TREATMENT OF nAMD - PROSPECTIVE TREAT & EXTEND DOSING LUCAS, TREND, TREX-AMD 15 Injections Mean = 8.9 Range = 8.0-10.1 10 10.5 Mean = 8.6 6.6 5 Mean Changei in ETDRS BCVA ETDRS in Changei Mean LUCAS Ranibizumab 0 LUCAS Bevacizumab 0 3 6 9 12 TREND Months TREX AMD Berg K, et al. Ophthalmology. 2015 Jan;122(1):146-52; Silva R, et al. Ophthalmology. 2018 Jan;125(1):57-65; Wykoff CC, et al. Ophthalmology. 2015 Dec;122(12):2514-22. REAL-WORLD DATA: MAJORITY OF nAMD PATIENTS LIKELY UNDERTREATED 1ST YEAR OF MANAGEMENT ≈73% ≤ 5 injections LUMINOUS 19.6 20 15 13.5 12.2 11.7 9.5 10 8.5 7.4 5.9 5.1 Proportion of patients (%) patients of Proportion 5 2.9 2.1 1.0 0.5 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 (n=250) (n=287) (n=661) (n=412) (n=455) (n=396) (n=322) (n=199) (n=173) (n=97) (n=72) (n=35) (n=17) (n=2) (n=1) Number of ranibizumab injections up to Month 12 Holz FG, et al. Presented at: EURetina 2017; September 7-10, 2017; Barcelona, Spain. KEY POINTS & ISSUES WITH CURRENT ANTI-VEGF-A THERAPY ▪ UPPER LIMIT FOR VA ~9 LETTERS FOR nAMD ▪ IMPROVEMENTS IN VA APPEAR DEPENDENT UPON ▪ NUMBER OF INTRAVITREAL INJECTIONS ▪ CLOSE MANAGEMENT OF ANATOMICAL CHANGES ▪ AVOID UNDERTREATMENT ▪ UNDER-TREATMENT IS COMMON AND PROHIBITS PATIENTS FROM ACHIEVING EXPECTED VA GAINS ▪ “MORE IS BETTER” BUT MAY COME AT A PRICE IN nAMD WHICH IS A CHRONIC DISEASE ▪ POSSIBILITY TO INDIVIDUALIZE TREATMENT WITH PRN OR TAE ▪ >12 WEEK TREATMENT INTERVAL POSSIBLE IN ~25-50% OF PATIENTS ▪ NEW TREATMENT MODALITIES INCLUDING COMBINATION THERAPY ARE NEEDED TO IMPROVE VISION AND/OR DURABILITY OF RESPONSE ▪ VEGF-A JUST ONE MOLECULAR PATHWAY IN THE PATHOGENESIS OF nAMD Wai KM et al. Am J Ophthalmic Clin Trials. 2018;1:1. ADDITIONAL ANTI-VEGF AGENTS DUAL-TARGETING BROLUCIZUMAB & ABICIPAR FARICIMAB INTO THE (RG7716) FUTURE VEGF-C/D BLOCKADE: OPT-302 MOONSHOTS C/D C/D Extra-Cellular - - Domains 1-3 DRUG DELIVERY VEGF ▪ GENE THERAPY VEGF hVEGFR-3 APPROACHES ▪ STEM CELLS ▪ DROPS ▪ PILLS hIgG1 Fc COMPARISON OF CURRENT VS EMERGING ANTI-VEGF-A AGENTS Bevacizumaba Ranibizumab Aflibercept Brolucizumabb Abicipar pegolb Monoclonal Single-chain Designed ankyrin Full antibody VEGFR-1/2-Fc Format humanized antibody fragment repeat protein (IgG1) fusion protein antibody fragment (scFv) (DARPin)1 Molecular structure Molecular weight 149 kDa 48 kDa 115 kDa 26 kDa 34 kDa Clinical dose 1.25 mg 0.5 mg 2.0 mg 6.0 mg 2.0 mg for nAMD (unlicensed use) aOff-label; not FDA-approved for any ocular indications bUnder investigation for treatment of nAMD 1. Molecular Partners. www.molecularpartners.com/our-products/abicipar/. Accessed 7/17/18. BROLUCIZUMAB: PHASE 3 STUDY DESIGN Dugel PU et al. Oral Presentation at the American Academy of Ophthalmology Meeting, Chicago, USA, October 2018. BROLUCIZUMAB WAS NON-INFERIOR TO AFLIBERCEPT Dugel PU et al. Oral Presentation at the American Academy of Ophthalmology Meeting, Chicago, USA, October 2018 BROLUCIZUMAB ACHIEVED SUPERIOR REDUCTIONS IN CENTRAL SUBFIELD THICKNESS (CST) AT WEEKS 16, 48 and 96.
Load more

Recommended publications
  • The Angiopoietin-2 and TIE Pathway As a Therapeutic Target for Enhancing Antiangiogenic Therapy and Immunotherapy in Patients with Advanced Cancer
    International Journal of Molecular Sciences Review The Angiopoietin-2 and TIE Pathway as a Therapeutic Target for Enhancing Antiangiogenic Therapy and Immunotherapy in Patients with Advanced Cancer Alessandra Leong and Minah Kim * Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032, USA; afl[email protected] * Correspondence: [email protected] Received: 26 September 2020; Accepted: 13 November 2020; Published: 18 November 2020 Abstract: Despite significant advances made in cancer treatment, the development of therapeutic resistance to anticancer drugs represents a major clinical problem that limits treatment efficacy for cancer patients. Herein, we focus on the response and resistance to current antiangiogenic drugs and immunotherapies and describe potential strategies for improved treatment outcomes. Antiangiogenic treatments that mainly target vascular endothelial growth factor (VEGF) signaling have shown efficacy in many types of cancer. However, drug resistance, characterized by disease recurrence, has limited therapeutic success and thus increased our urgency to better understand the mechanism of resistance to inhibitors of VEGF signaling. Moreover, cancer immunotherapies including immune checkpoint inhibitors (ICIs), which stimulate antitumor immunity, have also demonstrated a remarkable clinical benefit in the treatment of many aggressive malignancies. Nevertheless, the emergence of resistance to immunotherapies associated with an immunosuppressive tumor microenvironment has restricted therapeutic response, necessitating the development of better therapeutic strategies to increase treatment efficacy in patients. Angiopoietin-2 (ANG2), which binds to the receptor tyrosine kinase TIE2 in endothelial cells, is a cooperative driver of angiogenesis and vascular destabilization along with VEGF. It has been suggested in multiple preclinical studies that ANG2-mediated vascular changes contribute to the development and persistence of resistance to anti-VEGF therapy.
    [Show full text]
  • HY 2021 Results
    Roche HY 2021 results Basel, 22 July 2021 This presentation contains certain forward-looking statements. These forward-looking statements may be identified by words such as ‘believes’, ‘expects’, ‘anticipates’, ‘projects’, ‘intends’, ‘should’, ‘seeks’, ‘estimates’, ‘future’ or similar expressions or by discussion of, among other things, strategy, goals, plans or intentions. Various factors may cause actual results to differ materially in the future from those reflected in forward-looking statements contained in this presentation, among others: 1 pricing and product initiatives of competitors; 2 legislative and regulatory developments and economic conditions; 3 delay or inability in obtaining regulatory approvals or bringing products to market; 4 fluctuations in currency exchange rates and general financial market conditions; 5 uncertainties in the discovery, development or marketing of new products or new uses of existing products, including without limitation negative results of clinical trials or research projects, unexpected side-effects of pipeline or marketed products; 6 increased government pricing pressures; 7 interruptions in production; 8 loss of or inability to obtain adequate protection for intellectual property rights; 9 litigation; 10 loss of key executives or other employees; and 11 adverse publicity and news coverage. Any statements regarding earnings per share growth is not a profit forecast and should not be interpreted to mean that Roche’s earnings or earnings per share for this year or any subsequent period will necessarily match or exceed the historical published earnings or earnings per share of Roche. For marketed products discussed in this presentation, please see full prescribing information on our website www.roche.com All mentioned trademarks are legally protected.
    [Show full text]
  • Presentation
    ➢ ➢ ➢ ➢ ➢ ➢ • • • • • • • ✓ • • ✓ • • ✓ • • • o o o o o + = o o o o o O + P N O O Zhang et al, Effect of Salt on Phosphorylcholine-based Zwitterionic Polymer Brushes, Langmuir 2016, 32, 5048−5057 O Ishihara et al, Why do phospholipid polymers reduce protein adsorption? J. Biomed. Mater. Res. 1998, 39, 323−330. Schlenoff, Zwitteration: coating surfaces with zwitterionic functionality to reduce nonspecific adsorption. Langmuir 2014, 30, 9625−9636. Phosphorylcholine Yang et al, Salt-responsive zwitterionic polymer brushes with tunable friction and antifouling properties Langmuir 2015, 31, 9125−9133. 1.0 Conjugate Antibody Biopolymer PDI = 1.043 PDI = 1.002 PDI = 1.052 5.0 + = SCALE RELATIVE 0.0 7.0 8.0 9.0 10.0 150kD 800KD 950KD VOLUME (mL) Ranibizumab profile was adapted from Gaudreault et al, Invest Ophthalmol Vis Sci. 2005 46(2):726-33 KSI-301 profile was adjusted from 725µg/eye dose to 500µg/eye dose to match that of ranibizumab Yeung et al 2010 cancer research Interim data. Includes patients that reached the first retreatment opportunity (Week 12 visit) by the data cutoff date of 10 Oct 2019. Each bar represents an individual patient. All depicted patients continue to be followed (no discontinuations) Extended Durability in Exudative Retinal Diseases Using the Novel Intravitreal Anti-VEGF Antibody Biopolymer Conjugate KSI-301 First-time Results from a Phase 1b Study in Patients with wAMD, DME and RVO Charles C. Wykoff, MD, PhD Retina Consultants of Houston Houston, TX AAO Annual Meeting – Retina Subspecialty Day October 11, 2019 Disclosures ▪ Financial: Adverum (C, R); Aerpio (C, R); Alimera Sciences (C); Allegro (C); Allergan (C, R); Apellis (C, R); Bayer (C); Clearside Biomedical (C, R); Chengdu Kanghong (R); DORC (C); EyePoint (C); Fosun (C); Genentech/Roche (C, R); Iveric Bio (formerly Ophthotech) (C, R); Kodiak Sciences (C, R); Neurotech (R), Novartis (C, R); ONL Therapeutics (C); Opthea (R); PolyPhotonix (C); Recens Medical (C, R); Regeneron (C, R, S); Regenxbio (C, R); Samsung (R), Santen (C, R), Takeda (C).
    [Show full text]
  • Review of Neovascular Age-Related Macular Degeneration Treatment Options Nancy M
    REPORT Review of Neovascular Age-Related Macular Degeneration Treatment Options Nancy M. Holekamp, MD Disease Overview ABSTRACT Age-related macular degeneration (AMD) causes irreversible destruc- tion of the macula, which leads to loss of the sharp, fine-detail, Due to an aging population, visual impairment from neovascular “straight ahead” vision that is required for activities such as reading, age-related macular degeneration (nAMD) is increasing in the United driving, recognizing faces, and seeing in color. It is a leading cause of States. Despite unprecedented improvements in vision preservation that patients can achieve with anti-vascular endothelial growth factor (VEGF) irreversible visual impairment in the world.1,2 Over the past 15 years, agents, innovations are needed to reduce the burden of intravitreal anti-vascular endothelial growth factor (VEGF) agents have profoundly injections and improve outcomes in patients who do not respond transformed the management of neovascular AMD (nAMD) and are adequately to currently available agents. The best present option for credited with unprecedented improvements in vision preserva- vision preservation is a “zero-tolerance for fluid” schedule of monitoring tion and quality of life for millions of patients in the United States. and intravitreal injections that patients may need to follow for many years. This treatment burden has resulted in patients not achieving optimal After 2 years of treatment with an anti-VEGF agent, more than 95% benefit or even falling through the cracks. This article reviews state-of- of patients can expect to remain within 3 lines of their baseline the-art management approaches including as-needed and treat-and- visual acuity, and up to 40% can expect an improvement of 3 lines extend dosing regimens designed to reduce treatment burden.
    [Show full text]
  • Advances and Developments in Medical Retina
    FEATURE Advances and developments in medical retina BY ROD MCNEIL The author provides an update on late breaking clinical trial results in neovascular age-related macular degeneration (nAMD) and presentations on diabetes management from the American Academy of Ophthalmology Retina Subspecialty Day, held during the Academy’s annual meeting in Chicago, October 2018. Late breaking developments and predictive of continuing on that same four- or two-week adjustment increments, clinical trial results in nAMD quarterly treatment interval until week minimum treatment interval of eight weeks Brolucizumab in nAMD: HAWK and 96. Of the patients on brolucizumab 6mg and a maximum extension of 16 weeks) for HARRIER 96-week results who successfully completed year one on treatment naive nAMD patients through In the HAWK and HARRIER phase 3 nAMD a q12w dosing interval (i.e., 56% in HAWK 96 weeks. Mean BCVA gains from baseline (~55 letters) were 8.4 to 9.0 letters at week studies, the primary endpoint of non- and 51% in HARRIER), 82% in HAWK and 52 and 6.1 to 7.6 letters at week 96 for inferiority of brolucizumab 6mg (Novartis) 75% in HARRIER were maintained on a the four-week and two-week adjustment to aflibercept (Eylea®, Regeneron, Bayer) in q12w dosing interval in year two (overall, groups, respectively [4-6]. There was a mean change in best corrected visual acuity ~46% in HAWK and 38% in HARRIER). The mean of 10.4 injections given overall, (BCVA) from baseline was met at week 48 overall safety profile of brolucizumab was with a mean of 3.6 to 3.7 injections in the [1].
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • NETTER, Jr., Robert, C. Et Al.; Dann, Dorf- (21) International Application
    ll ( (51) International Patent Classification: (74) Agent: NETTER, Jr., Robert, C. et al.; Dann, Dorf- C07K 16/28 (2006.01) man, Herrell and Skillman, 1601 Market Street, Suite 2400, Philadelphia, PA 19103-2307 (US). (21) International Application Number: PCT/US2020/030354 (81) Designated States (unless otherwise indicated, for every kind of national protection av ailable) . AE, AG, AL, AM, (22) International Filing Date: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, 29 April 2020 (29.04.2020) CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, (25) Filing Language: English DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, (26) Publication Language: English KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, (30) Priority Data: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 62/840,465 30 April 2019 (30.04.2019) US OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, ST, SV, SY, TH, TJ, TM, TN, TR, (71) Applicants: INSTITUTE FOR CANCER RESEARCH TT, TZ, UA, UG, US, UZ, VC, VN, WS, ZA, ZM, ZW. D/B/A THE RESEARCH INSTITUTE OF FOX CHASE CANCER CENTER [US/US]; 333 Cottman Av¬ (84) Designated States (unless otherwise indicated, for every enue, Philadelphia, PA 191 11-2497 (US). UNIVERSTIY kind of regional protection available) . ARIPO (BW, GH, OF KANSAS [US/US]; 245 Strong Hall, 1450 Jayhawk GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, Boulevard, Lawrence, KS 66045 (US).
    [Show full text]
  • © 2021 Reachmd Page 1 of 8
    Transcriipt Detaiills This is a transcript of a continuing medical education (CME) activity accessible on the ReachMD network. Additional media formats for the activity and full activity details (including sponsor and supporter, disclosures, and instructions for claiming credit) are available by visiting: https://reachmd.com/programs/cme/advances-angiostatic-treatment-retinal-disease-demystifying-novel-therapeutic- targets/12490/ Released: 04/30/2021 Valid until: 04/30/2022 Time needed to complete: 30 minutes ReachMD www.reachmd.com [email protected] (866) 423-7849 Advances in Angiostatic Treatment for Retinal Disease: Demystifying Novel Therapeutic Targets Announcer: Welcome to CME on ReachMD. This activity entitled Advances in Angiostatic Treatment for Retinal Disease – Demystifying Novel Therapeutic Targets is provided by MedEdicus LLC and is supported by an independent education grant from Genentech Incorporated. Prior to beginning the activity, please be sure to review the faculty and commercial support disclosure statements, as well as the learning objectives. Dr. Eichenbaum: Welcome to Advances in Angiostatic Treatment for Retinal Disease – Demystifying Novel Therapeutic Targets . I’m David Eichenbaum, Collaborative Associate Professor of Ophthalmology at the Morsani College of Medicine at the University of South Florida and I’m Director of Research of Retina Vitreous Associates of Florida and Tampa Bay, Florida. I’m joined by my esteemed colleague and good friend, Charlie Wykoff, Director of Research at Retina Consultants of Texas
    [Show full text]
  • (INN) for Biological and Biotechnological Substances
    WHO/EMP/RHT/TSN/2019.1 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) 2019 WHO/EMP/RHT/TSN/2019.1 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) 2019 International Nonproprietary Names (INN) Programme Technologies Standards and Norms (TSN) Regulation of Medicines and other Health Technologies (RHT) Essential Medicines and Health Products (EMP) International Nonproprietary Names (INN) for biological and biotechnological substances (a review) FORMER DOCUMENT NUMBER: INN Working Document 05.179 © World Health Organization 2019 All rights reserved. Publications of the World Health Organization are available on the WHO website (www.who.int) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected]). Requests for permission to reproduce or translate WHO publications –whether for sale or for non-commercial distribution– should be addressed to WHO Press through the WHO website (www.who.int/about/licensing/copyright_form/en/index.html). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned.
    [Show full text]
  • Roche Q1 2021 Sales
    Roche Q1 2021 Sales Basel, 21 April 2021 This presentation contains certain forward-looking statements. These forward-looking statements may be identified by words such as ‘believes’, ‘expects’, ‘anticipates’, ‘projects’, ‘intends’, ‘should’, ‘seeks’, ‘estimates’, ‘future’ or similar expressions or by discussion of, among other things, strategy, goals, plans or intentions. Various factors may cause actual results to differ materially in the future from those reflected in forward-looking statements contained in this presentation, among others: 1 pricing and product initiatives of competitors; 2 legislative and regulatory developments and economic conditions; 3 delay or inability in obtaining regulatory approvals or bringing products to market; 4 fluctuations in currency exchange rates and general financial market conditions; 5 uncertainties in the discovery, development or marketing of new products or new uses of existing products, including without limitation negative results of clinical trials or research projects, unexpected side-effects of pipeline or marketed products; 6 increased government pricing pressures; 7 interruptions in production; 8 loss of or inability to obtain adequate protection for intellectual property rights; 9 litigation; 10 loss of key executives or other employees; and 11 adverse publicity and news coverage. Any statements regarding earnings per share growth is not a profit forecast and should not be interpreted to mean that Roche’s earnings or earnings per share for this year or any subsequent period will necessarily match or exceed the historical published earnings or earnings per share of Roche. For marketed products discussed in this presentation, please see full prescribing information on our website www.roche.com All mentioned trademarks are legally protected.
    [Show full text]
  • Improving Treatment Burden and Outcomes for Patients with Neovascular Age-Related Macular Degeneration Now and Into the Future
    199 AAO 2019_Novartis AMD Monograph_12pgs rev 2.qxp 1/31/20 1:20 PM Page 1 CME Monograph VISIT HTTPS://TINYURL.COM/NAMDCME FOR ONLINE TESTING AND INSTANT CME CERTIFICATE. IMPROVING TREATMENT BURDEN AND OUTCOMES FOR PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION NOW AND INTO THE FUTURE FACULTY NANCY M. HOLEKAMP, MD (CHAIR) PRAVIN U. DUGEL, MD BARUCH D. KUPPERMANN, MD, PHD CARL D. REGILLO, MD This continuing medical education activity is jointly provided by Original Release: March 1, 2020 New York Eye and Ear Infirmary of Mount Sinai and MedEdicus LLC. Expiration: March 31, 2021 This continuing medical education activity is supported through an unrestricted educational grant from Novartis Pharmaceuticals Corporation. Distributed with 199 AAO 2019_Novartis AMD Monograph_12pgs rev 2.qxp 1/31/20 1:20 PM Page 2 LEARNING METHOD AND MEDIUM NeoVista Inc; Neurotech Pharmaceuticals; Novartis Pharmaceuticals Corporation; This educational activity consists of a supplement and ten (10) study questions. Oculis; Omeros Corporation; Opthea; Optovue, Incorporated; Ora, Inc; Oxurion NV; The participant should, in order, read the learning objectives contained at the PanOptica; Pieris; QLT Inc; Regeneron Pharmaceuticals, Inc; Regenxbio Inc; beginning of this supplement, read the supplement, answer all questions in the ReNeuron Group PLC; Retinagenix; Santen Inc; SciFluor Life Sciences, Inc; Shire; post test, and complete the Activity Evaluation/Credit Request form. To receive Spark Therapeutics, Inc; Stealth BioTherapeutics Inc; Topcon Medical Systems, Inc; credit for this activity, please follow the instructions provided on the post test and TrueVision; and Zeiss; Ownership Interest (Stock options, or other holdings, Activity Evaluation/Credit Request form. This educational activity should take a excluding diversified mutual funds): Aerpio Therapeutics; Allegro Ophthalmics, LLC; maximum of 1.5 hours to complete.
    [Show full text]
  • A61K9/51 (2006.01) — with International Search Report (Art
    ) ( 2 (51) International Patent Classification: Published: A61K9/51 (2006.01) — with international search report (Art. 21(3)) (21) International Application Number: — before the expiration of the time limit for amending the PCT/US20 19/033 875 claims and to be republished in the event of receipt of amendments (Rule 48.2(h)) (22) International Filing Date: 24 May 2019 (24.05.2019) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/676,169 24 May 2018 (24.05.2018) US (71) Applicant: ELEKTROFI, INC. [US/US]; 75 Kneeland Street, 14th Floor, Boston, MA 021 11 (US). (72) Inventors: COFFMAN, Chase; 86 Worcester Street, Unit 3, Boston, MA 021 18 (US). CHARLES, Lyndon; 600 Main St Apt 3, Medford, MA 02155 (US). BROWN, Paul; 156 W 6th St, Unit 2, Boston, MA 02127 (US). DADON, Daniel, Benjamin; 2 Garden Court, Apt. 1, Cambridge, MA 02138 (US). LIU, Lisa; 111 Bartlett Street, Apt 2, Somerville, MA 02145 (US). SHADBAR, Sadiqua; 1307 Commonwealth Avenue, Apt 9, Allston, MA 02135 (US). SUDRIK, Chaitanya; 7 1 Elm Street, Apartment #2, Cam¬ bridge, MA 02139 (US). (74) Agent: BELLIVEAU, Michael J. et al.; Clark & Elbing LLP, 101 Federal Street, 15th Floor, Boston, MA 021 10 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available) : AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW.
    [Show full text]