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Denosumab Versus Romosozumab for Postmenopausal Osteoporosis Treatment
www.nature.com/scientificreports OPEN Denosumab versus romosozumab for postmenopausal osteoporosis treatment Tomonori Kobayakawa1, Akiko Miyazaki2, Makoto Saito3, Takako Suzuki2,4, Jun Takahashi2 & Yukio Nakamura2* Denosumab and romosozumab, a recently approved new drug, are efective and widely known molecular-targeted drugs for postmenopausal osteoporosis treatment. However, no studies have directly compared their therapeutic efects or safety in postmenopausal osteoporosis. This retrospective observational registry study compared the efcacy of 12-month denosumab or romosozumab treatment in postmenopausal osteoporosis patients. The primary outcome was the change in bone mineral density (BMD) at the lumbar spine. Secondary outcomes included BMD changes at the total hip and femoral neck, changes in bone turnover markers, and adverse events. Propensity score matching was employed to assemble patient groups with similar baseline characteristics. Sixty-nine patients each received either denosumab or romosozumab for 12 months. The mean 12-month percentage change from baseline in lumbar spine BMD was 7.2% in the denosumab group and 12.5% in the romosozumab group, indicating a signifcant diference between the groups. The percentage changes in BMD at both the total hip and femoral neck were also signifcantly higher at 12 months in the romosozumab group than in the denosumab group. In denosumab patients, bone formation and bone resorption markers were signifcantly decreased at 6 and 12 months from baseline. In the romosozumab group, the bone formation marker was signifcantly increased at 6 months and then returned to baseline, while the bone resorption marker was signifcantly decreased at both time points. Adverse events were few and predominantly minor in both groups, with no remarkable diference in the incidence of new vertebral fractures. -
AMGEN INC. V. SANOFI
Case: 20-1074 Document: 159 Page: 1 Filed: 06/21/2021 NOTE: This order is nonprecedential. United States Court of Appeals for the Federal Circuit ______________________ AMGEN INC., AMGEN MANUFACTURING, LIMITED, AMGEN USA, INC., Plaintiffs-Appellants v. SANOFI, AVENTISUB LLC, FKA AVENTIS PHARMACEUTICALS INC., REGENERON PHARMACEUTICALS INC., SANOFI-AVENTIS U.S. LLC, Defendants-Appellees ______________________ 2020-1074 ______________________ Appeal from the United States District Court for the District of Delaware in Nos. 1:14-cv-01317-RGA, 1:14-cv- 01349-RGA, 1:14-cv-01393-RGA, 1:14-cv-01414-RGA, Judge Richard G. Andrews. ______________________ JEFFREY A. LAMKEN, MoloLamken LLP, Washington, DC, filed a petition for rehearing en banc for plaintiffs-ap- pellants. Also represented by SARAH JUSTINE NEWMAN, MICHAEL GREGORY PATTILLO, JR.; SARA MARGOLIS, New York, NY; EMILY JOHNSON, ERICA S. OLSON, STEVEN TANG, STUART WATT, WENDY A. WHITEFORD, Amgen Inc., Thou- sand Oaks, CA; KEITH HUMMEL, Cravath Swaine & Moore LLP, New York, NY; WILLIAM G. GAEDE, III, McDermott Case: 20-1074 Document: 159 Page: 2 Filed: 06/21/2021 2 AMGEN INC. v. SANOFI Will & Emery LLP, Menlo Park, CA; CHRISTOPHER B. MEAD, Schertler Onorato Mead & Sears LLP, Washington, DC; JAMES L. HIGGINS, MELANIE K. SHARP, Young, Cona- way, Stargatt & Taylor, LLP, Wilmington, DE. Plaintiff- appellant Amgen Inc. also represented by SARAH CHAPIN COLUMBIA, McDermott, Will & Emery LLP, Boston, MA; LAUREN MARTIN, Quinn Emanuel Urquhart & Sullivan LLP, Boston, MA. MATTHEW WOLF, Arnold & Porter Kaye Scholer LLP, Washington, DC, filed a response for defendants-appellees. Also represented by VICTORIA REINES; DAVID K. BARR, DANIEL REISNER, New York, NY; DEBORAH E. -
Increased Bone Mineral Density for 1 Year of Romosozumab, Vs Placebo, Followed by 2 Years of Denosumab in the Japanese Subgroup
Archives of Osteoporosis (2019) 14:59 https://doi.org/10.1007/s11657-019-0608-z ORIGINAL ARTICLE Increased bone mineral density for 1 year of romosozumab, vs placebo, followed by 2 years of denosumab in the Japanese subgroup of the pivotal FRAME trial and extension Akimitsu Miyauchi1 & Rajani V. Dinavahi2 & Daria B. Crittenden2 & Wenjing Yang2 & Judy C. Maddox2 & Etsuro Hamaya3 & Yoichi Nakamura3 & Cesar Libanati4 & Andreas Grauer2 & Junichiro Shimauchi3 Received: 1 March 2019 /Accepted: 18 May 2019 # The Author(s) 2019 Abstract Summary Romosozumab, which binds sclerostin, rebuilds the skeletal foundation before transitioning to antiresorptive treat- ment. This subgroup analysis of an international, randomized, double-blind study in postmenopausal women with osteoporosis showed efficacy and safety outcomes for romosozumab followed by denosumab in Japanese women were generally consistent with those for the overall population. Purpose In the international, randomized, double-blind, phase 3 FRActure study, in postmenopausal woMen with ostEoporosis (FRAME; NCT01575834), romosozumab followed by denosumab significantly improved bone mineral density (BMD) and reduced fracture risk. This report evaluates Japanese women in FRAME. Methods Postmenopausal women with osteoporosis (T-score − 3.5 to − 2.5 at total hip or femoral neck) received romosozumab 210 mg or placebo subcutaneously monthly for 12 months, then each group received denosumab 60 mg subcutaneously every 6 months for 24 months. The key endpoint for Japanese women was BMD change. Other endpoints included new vertebral, clinical, and nonvertebral fracture; the subgroup analysis did not have adequate power to demonstrate statistically significant reductions. Results Of 7180 enrolled subjects, 492 (6.9%) were Japanese (247 romosozumab, 245 placebo). -
Denosumab, Raloxifene, Romosozumab and Teriparatide to Prevent Osteoporotic Fragility Fractures: a Systematic Review and Economic Evaluation
Journals Library Health Technology Assessment Volume 24 • Issue 29 • June 2020 ISSN 1366-5278 Denosumab, raloxifene, romosozumab and teriparatide to prevent osteoporotic fragility fractures: a systematic review and economic evaluation Sarah Davis, Emma Simpson, Jean Hamilton, Marrissa Martyn-St James, Andrew Rawdin, Ruth Wong, Edward Goka, Neil Gittoes and Peter Selby DOI 10.3310/hta24290 Denosumab, raloxifene, romosozumab and teriparatide to prevent osteoporotic fragility fractures: a systematic review and economic evaluation Sarah Davis ,1* Emma Simpson ,1 Jean Hamilton ,1 Marrissa Martyn-St James ,1 Andrew Rawdin ,1 Ruth Wong ,1 Edward Goka ,1 Neil Gittoes 2 and Peter Selby 3 1Health Economics and Decision Science, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK 2University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK 3School of Medical Sciences, University of Manchester, Manchester, UK *Corresponding author Declared competing interests of authors: Neil Gittoes reports personal fees for being a member of the advisory board to Union Chimique Belge (UCB) S.A. (Brussels, Belgium) and personal fees for contributing to educational meeting sponsored by Eli Lilly and Company (Indianapolis, IN, USA), outside the submitted work. He is also a trustee of the National Osteoporosis Society, a member of the advisory board of the National Osteoporosis Guideline Group and Deputy Chairperson of the Specialised Endocrinology Clinical Reference Group, NHS England. Published June 2020 DOI: 10.3310/hta24290 This report should be referenced as follows: Davis S, Simpson E, Hamilton J, James MM-S, Rawdin A, Wong R, et al. Denosumab, raloxifene, romosozumab and teriparatide to prevent osteoporotic fragility fractures: a systematic review and economic evaluation. -
Mark One) (X) QUARTERLY REPORT PURSUANT to SECTION 13 OR 15(D) of the SECURITIES EXCHANGE ACT of 1934
UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Form 10-Q (Mark One) (X) QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 1997 ------------------ OR ( ) TRANSITION REPORT PURSUANT TO SECTION 13 OR 15 (d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from _________ to _________ Commission File Number 0-19034 ------- REGENERON PHARMACEUTICALS, INC. ------------------------------------------------------ (Exact name of registrant as specified in its charter) New York 13-3444607 ------------------------------- ------------------------------------ (State or other jurisdiction of (I.R.S. Employer Identification No.) incorporation or organization) 777 Old Saw Mill River Road Tarrytown, New York 10591-6707 ---------------------------------------- ---------- (Address of principal executive offices) (Zip code) (914) 347-7000 ---------------------------------------------------- (Registrant's telephone number, including area code) Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes X No ----- ----- Indicate the number of shares outstanding of each of the issuer's classes of common stock as of November 3, 1997: Class of Common Stock -
Sixth Circuit I.O.P
RECOMMENDED FOR FULL-TEXT PUBLICATION Pursuant to Sixth Circuit I.O.P. 32.1(b) File Name: 15a0199p.06 UNITED STATES COURT OF APPEALS FOR THE SIXTH CIRCUIT _________________ DINO RIKOS et al., ┐ Plaintiffs-Appellees, │ │ │ No. 14-4088 v. │ > │ THE PROCTER & GAMBLE COMPANY, │ Defendant-Appellant. │ ┘ Appeal from the United States District Court for the Southern District of Ohio at Cincinnati. No. 1:11-cv-00226—Timothy S. Black, District Judge. Argued: June 16, 2015 Decided and Filed: August 20, 2015 Before: MOORE and COOK, Circuit Judges; COHN, District Judge.* _________________ COUNSEL ARGUED: Brian J. Murray, JONES DAY, Chicago, Illinois, for Appellant. Timothy G. Blood, BLOOD HURST & O’REARDON, San Diego, California, for Appellees. ON BRIEF: Brian J. Murray, JONES DAY, Chicago, Illinois, D. Jeffrey Ireland, FARUKI IRELAND & COX P.L.L., Cincinnati, Ohio, Joanne Lichtman, BAKER & HOSTETLER LLP, Cleveland, Ohio, Chad A. Readler, Rachel Bloomekatz, JONES DAY, Columbus, Ohio, for Appellant. Timothy G. Blood, Leslie E. Hurst, Thomas J. O’Reardon II, BLOOD HURST & O’REARDON, San Diego, California, for Appellees. MOORE, J., delivered the opinion of the court in which COHN, D.J., joined. COHN, D.J. (pg. 37), delivered a separate concurring opinion. COOK, J. (pp. 38–40), delivered a separate dissenting opinion. *The Honorable Avern Cohn, United States District Judge for the Eastern District of Michigan, sitting by designation. 1 No. 14-4088 Rikos et al. v. The Procter & Gamble Co. Page 2 _________________ OPINION _________________ KAREN NELSON MOORE, Circuit Judge. The named plaintiffs-appellees (“Plaintiffs”) are three individuals who purchased Align, Procter & Gamble’s (“P&G”) probiotic nutritional supplement, and found that the product did not work as advertised—that is, it did not promote their digestive health. -
Congress Report
ValEncia spain CONGRESS REPORT a proDucT of This publicaTion is supporTED by Foreword from Contents Anna Teti, ECTS president Progress for rare diseases at ECTS 1 ECTS 2018 supports Camurati- The ECTS 2018 congress was again Engelmann patients’ association 7 exciting and successful. Around ECTS perspectives on clinical hot topics 9 1000 delegates attended the Omics moving forward to practical translation 11 meeting in Valencia, for teaching and learning in a ECTS Steven Boonen Award 14 relaxed and lively atmosphere. Our pre-congress day Screening for fracture risk in osteoporosis 17 was also very successful and included the Mellanby training course, the first ECTS/ICCBH workshop on ECTS and ASBMR debate screening for fracture risk 19 Rare Bone Diseases, the East meets West events, 10 Bone and ageing 21 very successful Working Gro ups and the ECTS Risk factors for bone disease 24 Academy events. Scientists were able to take advantage of the networking opportunities, clinicians could hear Clinical weight loss and bone 28 about the latest developments and best clinical Management of clinical vertebral fractures 30 practice, and young investigators could benefit from Exploring the human microbiome 33 contact with experienced colleagues and opinion New data on efficacy of osteoporosis therapies 36 leaders, including through our Meet the Expert Advances in regenerative medicine 40 sessions. ECTS aims at promoting crosstalk between Fish as a model of skeletal diseases 42 the generations and we believe this goal was fully New insights into bone and cartilage biology 44 achieved in Valencia, particularly as a result of the Cancer and bone 48 tremendous efforts of our ECTS Academy members. -
Immunfarmakológia Immunfarmakológia
Gergely: Immunfarmakológia Immunfarmakológia Prof Gergely Péter Az immunpatológiai betegségek döntő többsége gyulladásos, és ennek következtében általában szövetpusztulással járó betegség, melyben – jelenleg – a terápia alapvetően a gyulladás csökkentésére és/vagy megszűntetésére irányul. Vannak kizárólag gyulladásgátló gyógyszereink és vannak olyanok, amelyek az immunreakció(k) bénításával (=immunszuppresszió révén) vagy emellett vezetnek a gyulladás mérsékléséhez. Mind szerkezetileg, mind hatástanilag igen sokféle csoportba oszthatók, az alábbi felosztás elsősorban didaktikus célokat szolgál. 1. Nem-szteroid gyulladásgátlók (‘nonsteroidal antiinflammatory drugs’ NSAID) 2. Kortikoszteroidok 3. Allergia-elleni szerek (antiallergikumok) 4. Sejtoszlás-gátlók (citosztatikumok) 5. Nem citosztatikus hatású immunszuppresszív szerek 6. Egyéb gyulladásgátlók és immunmoduláns szerek 7. Biológiai terápia 1. Nem-szteroid gyulladásgátlók (NSAID) Ezeket a vegyületeket, melyek őse a szalicilsav (jelenleg, mint acetilszalicilsav ‘aszpirin’ használatos), igen kiterjedten alkalmazzák a reumatológiában, az onkológiában és az orvostudomány szinte minden ágában, ahol fájdalom- és lázcsillapításra van szükség. Egyes felmérések szerint a betegek egy ötöde szed valamilyen NSAID készítményt. Szerkezetük alapján a készítményeket több csoportba sorolhatjuk: szalicilátok (pl. acetilszalicilsav) pyrazolidinek (pl. fenilbutazon) ecetsav származékok (pl. indometacin) fenoxiecetsav származékok (pl. diclofenac, aceclofenac)) oxicamok (pl. piroxicam, meloxicam) propionsav -
In the United States District Court for the District of Delaware
Case 1:20-cv-00561-UNA Document 1 Filed 04/24/20 Page 1 of 27 PageID #: 1 IN THE UNITED STATES DISTRICT COURT FOR THE DISTRICT OF DELAWARE AMGEN INC. and AMGEN MANUFACTURING, LIMITED, C.A. No. ________ Plaintiffs, v. HOSPIRA, INC. and PFIZER INC., DEMAND FOR JURY TRIAL Defendants. COMPLAINT Plaintiffs Amgen Inc. and Amgen Manufacturing, Limited (collectively, “Plaintiffs”), by and through their undersigned attorneys, for their Complaint against Defendants Hospira, Inc. and Pfizer Inc. (collectively, “Defendants”) hereby allege as follows: THE PARTIES 1. Amgen Inc. is a corporation existing under the laws of the State of Delaware, with its principal place of business at One Amgen Center Drive, Thousand Oaks, California, 91320. Amgen Inc. discovers, develops, manufactures, and sells innovative therapeutic products based on advances in molecular biology, recombinant DNA technology, and chemistry. Founded in 1980, Amgen Inc. is a pioneer in the development of biological human therapeutics. Today, Amgen Inc. is one of the largest biotechnology companies in the world, fueled in part by the success of NEUPOGEN® (filgrastim). 2. Amgen Manufacturing, Limited (“AML”) is a corporation existing under the laws of Bermuda with its principal place of business in Juncos, Puerto Rico. AML manufactures and sells biologic medicines for treating particular diseases in humans. AML is a wholly-owned subsidiary of Amgen Inc. Case 1:20-cv-00561-UNA Document 1 Filed 04/24/20 Page 2 of 27 PageID #: 2 3. On information and belief, Hospira, Inc. (“Hospira”) is a corporation existing under the laws of the State of Delaware, with its principal place of business at 275 North Field Drive, Lake Forest, Illinois 60045. -
The Two Tontti Tudiul Lui Hi Ha Unit
THETWO TONTTI USTUDIUL 20170267753A1 LUI HI HA UNIT ( 19) United States (12 ) Patent Application Publication (10 ) Pub. No. : US 2017 /0267753 A1 Ehrenpreis (43 ) Pub . Date : Sep . 21 , 2017 ( 54 ) COMBINATION THERAPY FOR (52 ) U .S . CI. CO - ADMINISTRATION OF MONOCLONAL CPC .. .. CO7K 16 / 241 ( 2013 .01 ) ; A61K 39 / 3955 ANTIBODIES ( 2013 .01 ) ; A61K 31 /4706 ( 2013 .01 ) ; A61K 31 / 165 ( 2013 .01 ) ; CO7K 2317 /21 (2013 . 01 ) ; (71 ) Applicant: Eli D Ehrenpreis , Skokie , IL (US ) CO7K 2317/ 24 ( 2013. 01 ) ; A61K 2039/ 505 ( 2013 .01 ) (72 ) Inventor : Eli D Ehrenpreis, Skokie , IL (US ) (57 ) ABSTRACT Disclosed are methods for enhancing the efficacy of mono (21 ) Appl. No. : 15 /605 ,212 clonal antibody therapy , which entails co - administering a therapeutic monoclonal antibody , or a functional fragment (22 ) Filed : May 25 , 2017 thereof, and an effective amount of colchicine or hydroxy chloroquine , or a combination thereof, to a patient in need Related U . S . Application Data thereof . Also disclosed are methods of prolonging or increasing the time a monoclonal antibody remains in the (63 ) Continuation - in - part of application No . 14 / 947 , 193 , circulation of a patient, which entails co - administering a filed on Nov. 20 , 2015 . therapeutic monoclonal antibody , or a functional fragment ( 60 ) Provisional application No . 62/ 082, 682 , filed on Nov . of the monoclonal antibody , and an effective amount of 21 , 2014 . colchicine or hydroxychloroquine , or a combination thereof, to a patient in need thereof, wherein the time themonoclonal antibody remains in the circulation ( e . g . , blood serum ) of the Publication Classification patient is increased relative to the same regimen of admin (51 ) Int . -
Romosozumab Monoclonal Antibody- Sclerostin
ROMOSOZUMAB MONOCLONAL ANTIBODY- SCLEROSTIN JOSEPH M. LANE, MD HOSPITAL FOR SPECIAL SURGERY Weill Cornell Medicine NEW YORK, NY Disclosure Joseph M. Lane, MD CollPlant, Inc: Stock Options Merck: Research Support On Foundation: Consultant/Board Member Radius Health, Inc: Consultant Terumo BCT Consultant NIH Study Section Research Grants OSTEOPOROSIS Fragility (Iow energy) Fractures Hip Fracture Mortality (1 year) Female ~ 24% Male ~ 30% 70% Lose One Level Function ANTIRESORPTION Bisphosphonates ↓R ↓F Denosumab ↓R SERMS ↓R Only spine ANABOLIC Teriparatide ↑F Late ↑R Abaloparatide ↑F Late ↑R ROM0S0ZUMAB ↑F ↓R ROMOSOZUMAB SCLEROSTIN MONOCLONAL ANTIBODY WHAT DO WE KNOW ABOUT SCLEROSTIN? Odd diseases Wnt Bone Pathway SCLEROSTIOSIS Inactivating Mutation SOST (codes for sclerostin) van Buchan Disease less severe ↑ Bone Mass ↓ Fractures SCLEROSTIN Secreted By Osteocyte (low mechanical load) Binds to LRP 5/6 Inactivates Wnt Pathway Ceases Osteoblastic Bone Formation Shah AD et al. Int J Womens Health, 2015. Pre-Clinical Data Romosozumab Genetic Deficiency Sclerostin Rodents ↑Bone Mass ↑ Bone Formation Trabecular Cortical Normal Bone Quality ↑Bone Strength Normal Mineralization Lack of Brittleness Sclerostin Monoclonal Antibody Animals ↑ Trabecular/Cortical Thickness ↓ Cortical Porosity Corrected Ovariectomy ↑ Bone Density LS, FN, Prox Tib, Distal Radius RANKL INHIBITOR AMPLIFIED GAIN Comparison of Changes in Areal And Volumetric BMD 12 Months Romo vs Teriparatide Romo Teriparatide 210mg qm 20ug/d Areal BMD (DXA) L-Spine 12.3%* 6.9%* Total Hip 3.9%* 0.8% Integral V-metric BMD (QCT) 17.7% * L-Spine 4.1% 12.9%* Total Hip 1.2% * p<.05 Genant JBMR 2017 Comparison of Changes in Estimated Bone Strength Finite Element Analyses Romo Teriparatide 210mg qm 20μg/d Estimated Bone Strength FEA by QCT 27.3%* 18.5% L-Spine 12.3%* 3.6%* 18.5% Total Hip -0.7% * p<.05 Keaveny JBMR 2017 Romosozumab vs. -
Surprises in the Industry's Most Profitable Companies
June 20, 2008 Surprises in the industry's most profitable companies Evaluate Vantage An analysis of the industry’s most profitable companies last year throws up some surprising names within the top ten – ViroPharma tops the league table with a net income margin of 47%, generating all its profits from sales of anti-bacterial agent Vancocin. Interestingly, two Indian generic firms feature, Sun Pharmaceutical Industries and Glenmark Pharmaceuticals, perhaps dispelling the notion that margins from selling generics are always low. Of the big pharma players, only those US groups with mature product portfolios, namely Pfizer, Merck & Co and Amgen, make it into the list. However, looking at forecast margins for the current year, the table below also reveals that Merck & Co drops out of the top ten, impacted by significantly lower sales from its cholesterol franchise. Alcon replaces Merck, suggesting one good reason why Novartis recently decided to fork out $11bn to acquire a 25% stake in the eye-care company. This analysis from EvaluatePharma is based on dividing normalised net income (excluding exceptional items) by the total revenues, to generate a net margin percentage. It only includes companies that have reported two consecutive years of profit, with incomes in excess of $50m in both 2007 and 2008. 2007 - top 10 companies Net Margin Net Income - Normalised ($m) Total Revenues ($m) 2007 2006 2007 2007 ViroPharma 47% 66 95 204 Sun Pharmaceutical Industries 44% 159 371 837 Gilead Sciences 38% 1,204 1,615 4,230 Biovail 35% 428 293 843 OSI Pharmaceuticals