Μελλοντικές κατευθύνσεις στην αγωγή της οστεοπόρωσης

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Kerrie Snow
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1 Μελλοντικές κατευθύνσεις στην αγωγή της οστεοπόρωσης Δρ Χρήστος Κ. Κοσμίδης Ορθοπεδικός

2 ΔΙΑΘΕΣΙΜΑ ΑΝΤΙΟΣΤΕΟΠΟΡΩΤΙΚΑ ΦΑΡΜΑΚΑ Διφωσφονικά Αλενδρονάτη Ρισεδρονάτη Ιμπανδρονάτη Ζολεδρονάτη Δενοσουμάμπη SERMs Ραλοξιφαίνη Μπαζεντοξιφαίνη Ρανελικό στρόντιο Τεριπαρατίδη PTH 1-84 Αντικαταβολικά Διπλής δράσεως Αναβολικά

3 Ασθενής με T-score < -3,0 και ταυτόχρονο ιστορικό κατάγματος ισχίου ή σπονδύλου ή 2 άλλων μη σπονδυλικών καταγμάτων, δύναται να αρχίσει αγωγή πρόληψης νέων καταγμάτων με τεριπαρατίδη (μεταξύ και άλλων επιλογών).

4 Abaloparatide ( PTHrP 1-34 πεπτίδιο, µε 13 κοινά αµινοξέα µε την Τεριπαρατίδη) ELADYNOS

5 Μελέτες

6 JAMA. 2016;316(7): Effect of Abalopara/de vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis A Randomized Clinical Trial Paul D. Miller, MD; Gary Haversley, PhD; Bente Juel Riis, MD; Gregory C. Williams, PhD; Edith Lau, MD; Luis Augusto Russo,MD, PhD; Peter Alexandersen, MD; Cris ano A. F. Zerbini, MD; Ming-yi Hu, PhD; Alan G. Harris, MD; Lorraine A. Fitzpatrick, MD; Felicia Cosman, MD; Claus Chris ansen, MD; for the ACTIVE Study Inves gators Postmenopausal women (mean age, 69 years [range, 49-86]) with bone mineral density (BMD) T score 2.5 and > 5.0 at the lumbar spine or femoral neck and radiological evidence 2 mild or 1 moderate lumbar or thoracic vertebral fracture or history of low-trauma nonvertebral fracture within the past 5 years were eligible. Postmenopausal women (>65 y) with fracture criteria and a T score 2.0 and > 5.0 or without fracture criteria and a T score 3.0 and > 5.0 could enroll. Blinded, daily subcutaneous injec ons of placebo (n = 821); abalopara de, 80 μg (n = 824); or open-label teripara de, 20 μg (n = 818) for 18 months.

7 Βιοχημικοί δείκτες

8 JAMA. 2016;316(7): Effect of Abalopara/de vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis A Randomized Clinical Trial

9 JAMA. 2016;316(7): Effect of Abalopara/de vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis A Randomized Clinical Trial

Endocrinology. 2016 Jan; 157(1): 141 149.

10 Endocrinology Jan; 157(1): Binding Selec/vity of Abalopara/de for PTH-Type-1-Receptor Conforma/ons and Effects on Downstream Signaling Gary Haversley, Thomas Dean, Braden A. Corbin, Hila Bahar, and Thomas J. Gardella corresponding author

11 Endocrinology Jan; 157(1): Binding Selec/vity of Abalopara/de for PTH-Type-1-Receptor Conforma/ons and Effects on Downstream Signaling Gary Haversley, Thomas Dean, Braden A. Corbin, Hila Bahar, and Thomas J. Gardella corresponding author

12 Endocrinology Jan; 157(1): Binding Selec/vity of Abalopara/de for PTH-Type-1-Receptor Conforma/ons and Effects on Downstream Signaling Gary Haversley, Thomas Dean, Braden A. Corbin, Hila Bahar, and Thomas J. Gardella corresponding author

13 Endocrinology Jan; 157(1): Binding Selec/vity of Abalopara/de for PTH-Type-1-Receptor Conforma/ons and Effects on Downstream Signaling Gary Haversley, Thomas Dean, Braden A. Corbin, Hila Bahar, and Thomas J. Gardella corresponding author The hypothesis tested here was that ABL compared with PTH (1 34) binds with rela/vely greater selec/vity to the RG of the PTHR1 vs the R0 conforma on and thus mediates more transient cell signaling responses. This hypothesis was based on results of studies in animals (3, 4) and in humans (2), which suggest that daily injec on of ABL is more effec ve at inducing net bone-anabolic responses in vivo than is daily injec on of PTH (1 34), as such a favoring of bone-forma/on vs bone-resorp/on/calcemic effects is associated with intermipent as opposed to con/nuous PTH ligand exposure. We found that ABL indeed exhibited greater selec vity for the RG receptor conforma on than did PTH (1 34). ABL thus bound to RG with an affinity similar to that of PTH (1 34) while it bound to R0 with a considerably lower affinity. The high RG selec/vity (lower R0 affinity) observed for ABL was associated with more transient camp signaling responses compared with the responses induced by PTH. The effect was especially drama c when compared with the responses induced by the long-ac ng analog, LA-PTH, which binds with par cularly high affinity to the R0 conforma on (11). The findings are thus consistent with our hypothesis that the more favorable effects on bone metabolism seen with ABL compared with PTH (1 34) in preclinical and clinical studies arise, at least in part, from a more selec ve binding of the analog to the RG PTHR1 conforma on.

14 Οστική πυκνότητα

15 JAMA. 2016;316(7): Effect of Abalopara/de vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis A Randomized Clinical Trial

16 JAMA. 2016;316(7): Effect of Abalopara/de vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis A Randomized Clinical Trial

17 JAMA. 2016;316(7): Effect of Abalopara/de vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis A Randomized Clinical Trial

18 Κατάγματα

19 JAMA. 2016;316(7): Effect of Abalopara/de vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis A Randomized Clinical Trial

20 Ανεπιθύμητες ενέργειες

21 JAMA. 2016;316(7): Effect of Abalopara/de vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis A Randomized Clinical Trial

22 Eighteen Months of Treatment With Subcutaneous Abaloparatide Followed by 6 Months of Treatment With Alendronate in Postmenopausal Women With Osteoporosis Results of the ACTIVExtend Trial Felicia Cosman, MD, Paul D. Miller, MD, Gregory C. Williams, PhD, Gary Hattersley, PhD, Ming-yi Hu, PhD, Ivo Valter, MD, Lorraine A. Fitzpatrick, MD, Bente Juel Riis, MD, Claus Christiansen, MD, John P. Bilezikian, MD, Dennis Black, PhD Mayo Clinic Proceedings ςολυµε 92, Ισσυε 2, Παγεσ (Φεβρυαρψ 2017) ΔΟΙ: /ϕ.µαψοχπ

Φιγυρε 1 Mayo Clinic Proceedings 2017 92,

23 Φιγυρε 1 Mayo Clinic Proceedings , ΔΟΙ: ( /ϕ.µαψοχπ )

24 Φιγυρε 4 LS Total Hip FN Mayo Clinic Proceedings , ΔΟΙ: ( /ϕ.µαψοχπ )

Φιγυρε 2 Mayo Clinic Proceedings 2017 92,

25 Φιγυρε 2 Mayo Clinic Proceedings , ΔΟΙ: ( /ϕ.µαψοχπ )

26 Φιγυρε 3 Mayo Clinic Proceedings , ΔΟΙ: ( /ϕ.µαψοχπ )

27 The study was funded by Radius Health. Dr Bone is a consultant for Amgen. Dr Genant is a cofounder and senior consultant for Synarc. American Society for Bone and Mineral Research. September 10, 2017, Denver, Colorado. Abstract To further evaluate abalopara de's effects in that type of maintenance sežng, the ACTIVExtend trial, which began a month aÿer the original 18 months, involved pa ents in both groups who were switched to treatments of alendronate 70 mg weekly for 2 years, including 581 in the original placebo group and 558 in the original abalopara de group. Over the course of the combined trials 43 months five of 544 evaluable women (0.9%) in the abalopara de group had at least one new vertebral fracture compared with 32 of 568 (5.6%) in the placebo group, represen ng an 84% rela/ve risk reduc/on (P <.001). In terms of nonvertebral fractures, the abalopara de group had a 39% risk reduc/on in the ACTIVExtend results, with 27 fractures (5%) compared with 45 (8%) in the placebo group (P =.03).

28 U.S. Department of Health and Human Services FDA U.S. FOOD & DRUG ADMINISTRATION TYMLOS (abalopara/de) Radius Health, Inc. Approval date: April 28, 2017

29 Radius Health Announces that the Committee for Medicinal Products for Human Use (CHMP) Has Issued a Second Day-180 List of Outstanding Issues in its Regulatory Review of Eladynos (Abaloparatide-SC), a Bone Building Agent for the Treatment of Postmenopausal Women with Osteoporosis at High Risk for Fracture Radius Health anticipates an opinion from the CHMP regarding the MAA for Eladynos (abaloparatide-sc) before year-end WALTHAM, Mass., July 21, 2017 (GLOBE NEWSWIRE) -- Radius Health, Inc. (Nasdaq:RDUS), a science-driven fully integrated biopharmaceutical company that is committed to developing and commercializing innovative therapeutics in the areas of osteoporosis, oncology and endocrine diseases, today announced that on July 21, 2017 the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), issued a second Day-180 List of Outstanding Issues and requested additional data analyses related to the safety and efficacy of abaloparatide-sc in the process of their ongoing regulatory review. Radius expects the CHMP to issue an opinion regarding the MAA for abaloparatide-sc prior to the end of 2017.

30 ;

31 Romosozumab Μονοκλωνικό αντίσωμα, αναστολέας της σκληροστίνης EVENITY

Romosozumab Exerts a Dual Effect on Bone, Increasing Bone Forma on and Decreasing Bone Resorp on 1-3 1. Cosman F, et al.

32 Romosozumab Exerts a Dual Effect on Bone, Increasing Bone Forma on and Decreasing Bone Resorp on Cosman F, et al. N Engl J Med (In press). 2. McClung MR, et al. N Engl J Med. 2014;370: Baron R. Nat Med. 2013;19:

33 Romosozumab development Phase 3 program in bone loss disorders EU Registra/on studies in osteoporosis STRUCTURE FRAME BRIDGE ARCH (NCT ) 1 (NCT ) 2 (NCT ) 3 (NCT ) pa/ents (postmenopausal women) pa/ents (postmenopausal women) 245 pa/ents (men) pa/ents (postmenopausal women) Treatment 12 months romosozumab 12 months romosozumab followed by 12 months denosumab 12 months romosozumab 12 months romosozumab followed by alendronate Comparator 12 months teripara:de 12 months placebo followed by 12 months denosumab 12 months placebo Alendronate 1 ary Endpoint % change from baseline in DXA BMD at the hip through month 12 Incidence of new vertebral fracture - 12 and 24 months % change from baseline in DXA BMD at the lumbar spine at month 12 Incidence of clinical fracture (event driven) + incidence of new vertebral fractures at month 24 Study comple/on hvps://clinicaltrials.gov/ct2/show/nct ?term=romosozumab&rank=13;2. hvps://clinicaltrials.gov/ct2/show/nct ?term=romosozumab&rank=15; 3. hvps://clinicaltrials.gov/ct2/show/nct ?term=romosozumab&rank=5 ; 4. hvps://clinicaltrials.gov/ct2/show/nct ?term=romosozumab&rank=4;

34 Μελέτες

35 FRAME Phase 3 Study Design FRActure study in postmenopausal women with osteoporosis E N R O L L M E N T 1:1 N = 7,180 Month 0* Spine x-rays DXA BTMs Double-blind Romosozumab 210 mg SC QM (N = 3,589) Placebo SC QM (N = 3,591) 6 Open-label Denosumab 60 mg SC Q6M Denosumab 60 mg SC Q6M to 1,000 mg calcium daily 600 to 800 IU vitamin D daily E X T E N S I O N 12 months *A loading dose of 50,000-60,000 IU vitamin D was given to subjects with a baseline serum vitamin D 25(OH)D level of 40 ng/ml. Cosman F, et al. N Engl J Med DOI: /NEJMoa Inclusion: Postmenopausal women age 55 to 90 years BMD T-score -2.5 at the total hip or femoral neck Exclusion: BMD T-score -3.5 at the total hip or femoral neck History of hip fracture, or any severe or more than 2 moderate vertebral fractures Recent osteoporosis therapy (washout period varied by agent) Co-Primary Endpoints: Subject incidence of new vertebral fracture through 12 and 24 months Secondary Fracture Endpoints: Clinical, nonvertebral, and other fracture categories through 12 and 24 months

N Engl J Med 2016;375:1532-43. Romosozumab Treatment in Postmenopausal Women with Osteoporosis F. Cosman, D.B. Crivenden, J.D. Adachi, N. Binkley, E.

36 N Engl J Med 2016;375: Romosozumab Treatment in Postmenopausal Women with Osteoporosis F. Cosman, D.B. Crivenden, J.D. Adachi, N. Binkley, E. Czerwinski, S. Ferrari, L.C. Ho auer, E. Lau, E.M. Lewiecki, A. Miyauchi, C.A.F. Zerbini, C.E. Milmont, L. Chen, J. Maddox, P.D. Meisner, C. Libana, and A. Grauer

37 Βιοχημικοί δείκτες

38 N Engl J Med 2016;375: Romosozumab Treatment in Postmenopausal Women with Osteoporosis F. Cosman, D.B. Crivenden, J.D. Adachi, N. Binkley, E. Czerwinski, S. Ferrari, L.C. Ho auer, E. Lau, E.M. Lewiecki, A. Miyauchi, C.A.F. Zerbini, C.E. Milmont, L. Chen, J. Maddox, P.D. Meisner, C. Libana, and A. Grauer

39 Οστική πυκνότητα

40 N Engl J Med 2016;375: Romosozumab Treatment in Postmenopausal Women with Osteoporosis F. Cosman, D.B. Crivenden, J.D. Adachi, N. Binkley, E. Czerwinski, S. Ferrari, L.C. Ho auer, E. Lau, E.M. Lewiecki, A. Miyauchi, C.A.F. Zerbini, C.E. Milmont, L. Chen, J. Maddox, P.D. Meisner, C. Libana, and A. Grauer

41 Κατάγματα

42 N Engl J Med 2016;375: Romosozumab Treatment in Postmenopausal Women with Osteoporosis F. Cosman, D.B. Crivenden, J.D. Adachi, N. Binkley, E. Czerwinski, S. Ferrari, L.C. Ho auer, E. Lau, E.M. Lewiecki, A. Miyauchi, C.A.F. Zerbini, C.E. Milmont, L. Chen, J. Maddox, P.D. Meisner, C. Libana, and A. Grauer

43 N Engl J Med 2016;375: Romosozumab Treatment in Postmenopausal Women with Osteoporosis F. Cosman, D.B. Crivenden, J.D. Adachi, N. Binkley, E. Czerwinski, S. Ferrari, L.C. Ho auer, E. Lau, E.M. Lewiecki, A. Miyauchi, C.A.F. Zerbini, C.E. Milmont, L. Chen, J. Maddox, P.D. Meisner, C. Libana, and A. Grauer

$Subject Incidence of Nonvertebral Fracture in La n America vs Rest-of-World Through Month 12 n/n1 = number of subjects with fractures/number$

44 Subject Incidence of Nonvertebral Fracture in La n America vs Rest-of-World Through Month 12 n/n1 = number of subjects with fractures/number of subjects in the full analysis set. *Regions excluding La n America grouped post hoc. Cosman F, et al. N Engl J Med. 2016, 375(16):

45 Ανεπιθύμητες ενέργειες

46 N Engl J Med 2016;375: Romosozumab Treatment in Postmenopausal Women with Osteoporosis F. Cosman, D.B. Crivenden, J.D. Adachi, N. Binkley, E. Czerwinski, S. Ferrari, L.C. Ho auer, E. Lau, E.M. Lewiecki, A. Miyauchi, C.A.F. Zerbini, C.E. Milmont, L. Chen, J. Maddox, P.D. Meisner, C. Libana, and A. Grauer

47 2 Cases of Posi vely Adjudicated Osteonecrosis of the Jaw (ONJ) Cosman F, et al. N Engl J Med. 2016, 375(16):

48 1 Case of Posi vely Adjudicated Atypical Femoral Fractures (AFF) Cosman F, et al. N Engl J Med. 2016, 375(16):

49 Lancet, Published online July 26, 2017 Romosozumab (scleros/n monoclonal an/body) versus teripara/de in postmenopausal women with osteoporosis transi/oning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial Bente L Langdahl, Cesar Libana:, Daria B CriCenden, Michael A Bolognese, Jacques P Brown, Nadia S Daizadeh, Eva Dokoupilova, Klaus Engelke, Joel S Finkelstein, Harry K Genant, Stefan Goemaere, Lars Hyldstrup, Esteban Jodar-Gimeno, Tony M Keaveny, David Kendler, Peter Lakatos, Judy Maddox, Jorge Malouf, Fabio E Massari, Jose Fernando Molina, Maria Rosa Ulla, Andreas Grauer We enrolled women (aged 55 to 90 years) with postmenopausal osteoporosis who had taken an oral bisphosphonate for at least 3 years before screening and alendronate the year before screening; an areal BMD T score of 2 5 or lower at the total hip, femoral neck, or lumbar spine; and a history of fracture. Pa/ents were randomly assigned (1:1) via an interac/ve voice response system to receive subcutaneous romosozumab (210 mg once monthly) or subcutaneous teripara/de (20 μg once daily) for 12 months.

50 Βιοχημικοί δείκτες

51 Lancet, Published online July 26, 2017 Romosozumab (scleros/n monoclonal an/body) versus teripara/de in postmenopausal women with osteoporosis transi/oning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial Bente L Langdahl, Cesar Libana:, Daria B CriCenden, Michael A Bolognese, Jacques P Brown, Nadia S Daizadeh, Eva Dokoupilova, Klaus Engelke, Joel S Finkelstein, Harry K Genant, Stefan Goemaere, Lars Hyldstrup, Esteban Jodar-Gimeno, Tony M Keaveny, David Kendler, Peter Lakatos, Judy Maddox, Jorge Malouf, Fabio E Massari, Jose Fernando Molina, Maria Rosa Ulla, Andreas Grauer

52 Οστική πυκνότητα ποιότητα - αντοχή

53 Lancet, Published online July 26, 2017 Romosozumab (scleros/n monoclonal an/body) versus teripara/de in postmenopausal women with osteoporosis transi/oning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial Bente L Langdahl, Cesar Libana:, Daria B CriCenden, Michael A Bolognese, Jacques P Brown, Nadia S Daizadeh, Eva Dokoupilova, Klaus Engelke, Joel S Finkelstein, Harry K Genant, Stefan Goemaere, Lars Hyldstrup, Esteban Jodar-Gimeno, Tony M Keaveny, David Kendler, Peter Lakatos, Judy Maddox, Jorge Malouf, Fabio E Massari, Jose Fernando Molina, Maria Rosa Ulla, Andreas Grauer BMD

54 Lancet, Published online July 26, 2017 Romosozumab (scleros/n monoclonal an/body) versus teripara/de in postmenopausal women with osteoporosis transi/oning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial Bente L Langdahl, Cesar Libana:, Daria B CriCenden, Michael A Bolognese, Jacques P Brown, Nadia S Daizadeh, Eva Dokoupilova, Klaus Engelke, Joel S Finkelstein, Harry K Genant, Stefan Goemaere, Lars Hyldstrup, Esteban Jodar-Gimeno, Tony M Keaveny, David Kendler, Peter Lakatos, Judy Maddox, Jorge Malouf, Fabio E Massari, Jose Fernando Molina, Maria Rosa Ulla, Andreas Grauer QCT

55 Lancet, Published online July 26, 2017 Romosozumab (scleros/n monoclonal an/body) versus teripara/de in postmenopausal women with osteoporosis transi/oning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial Bente L Langdahl, Cesar Libana:, Daria B CriCenden, Michael A Bolognese, Jacques P Brown, Nadia S Daizadeh, Eva Dokoupilova, Klaus Engelke, Joel S Finkelstein, Harry K Genant, Stefan Goemaere, Lars Hyldstrup, Esteban Jodar-Gimeno, Tony M Keaveny, David Kendler, Peter Lakatos, Judy Maddox, Jorge Malouf, Fabio E Massari, Jose Fernando Molina, Maria Rosa Ulla, Andreas Grauer

56 Journal of Bone and Mineral Research, Vol. 32, No. 9, September 2017, pp Greater Gains in Spine and Hip Strength for Romosozumab Compared With Teripara/de in Postmenopausal Women With Low Bone Mass Tony M Keaveny, Daria B Crivenden, Michael A Bolognese, Harry K Genant, Klaus Engelke, Beatriz Oliveri, Jacques P Brown, Bente L Langdahl, Chris Yan, Andreas Grauer, and Cesar Libana

57 Journal of Bone and Mineral Research, Vol. 32, No. 9, September 2017, pp Greater Gains in Spine and Hip Strength for Romosozumab Compared With Teripara/de in Postmenopausal Women With Low Bone Mass Tony M Keaveny, Daria B Crivenden, Michael A Bolognese, Harry K Genant, Klaus Engelke, Beatriz Oliveri, Jacques P Brown, Bente L Langdahl, Chris Yan, Andreas Grauer, and Cesar Libana

58 The new england journal of medicine September 11, 2017 DOI: /NEJMoa Romosozumab or Alendronate for Fracture Preven/on in Women with Osteoporosis Kenneth G. Saag, M.D., Jeffrey Petersen, M.D., Maria Luisa Brandi, M.D., Andrew C. Karaplis, M.D., Ph.D., Mažas Lorentzon, M.D., Ph.D., Thierry Thomas, M.D., Ph.D., Judy Maddox, D.O., Michelle Fan, Ph.D., Paul D. Meisner, Pharm.D., and Andreas Grauer, M.D. We enrolled 4093 postmenopausal women...with osteoporosis and a fragility fracture......and randomly assigned them in a 1:1 ra o to receive......monthly subcutaneous romosozumab (210 mg).....or weekly oral alendronate (70 mg)......in a blinded fashion for 12 months, followed by open-label alendronate in both groups.

59 The new england journal of medicine September 11, 2017 DOI: /NEJMoa Romosozumab or Alendronate for Fracture Preven/on in Women with Osteoporosis Kenneth G. Saag, M.D., Jeffrey Petersen, M.D., Maria Luisa Brandi, M.D., Andrew C. Karaplis, M.D., Ph.D., Mažas Lorentzon, M.D., Ph.D., Thierry Thomas, M.D., Ph.D., Judy Maddox, D.O., Michelle Fan, Ph.D., Paul D. Meisner, Pharm.D., and Andreas Grauer, M.D.

60 Βιοχημικοί δείκτες

61 The new england journal of medicine September 11, 2017 DOI: /NEJMoa Romosozumab or Alendronate for Fracture Preven/on in Women with Osteoporosis Kenneth G. Saag, M.D., Jeffrey Petersen, M.D., Maria Luisa Brandi, M.D., Andrew C. Karaplis, M.D., Ph.D., Mažas Lorentzon, M.D., Ph.D., Thierry Thomas, M.D., Ph.D., Judy Maddox, D.O., Michelle Fan, Ph.D., Paul D. Meisner, Pharm.D., and Andreas Grauer, M.D.

62 Οστική πυκνότητα

63 The new england journal of medicine September 11, 2017 DOI: /NEJMoa Romosozumab or Alendronate for Fracture Preven/on in Women with Osteoporosis Kenneth G. Saag, M.D., Jeffrey Petersen, M.D., Maria Luisa Brandi, M.D., Andrew C. Karaplis, M.D., Ph.D., Mažas Lorentzon, M.D., Ph.D., Thierry Thomas, M.D., Ph.D., Judy Maddox, D.O., Michelle Fan, Ph.D., Paul D. Meisner, Pharm.D., and Andreas Grauer, M.D.

64 Κατάγματα

65 The new england journal of medicine September 11, 2017 DOI: /NEJMoa Romosozumab or Alendronate for Fracture Preven/on in Women with Osteoporosis Kenneth G. Saag, M.D., Jeffrey Petersen, M.D., Maria Luisa Brandi, M.D., Andrew C. Karaplis, M.D., Ph.D., Mažas Lorentzon, M.D., Ph.D., Thierry Thomas, M.D., Ph.D., Judy Maddox, D.O., Michelle Fan, Ph.D., Paul D. Meisner, Pharm.D., and Andreas Grauer, M.D.

66 The new england journal of medicine September 11, 2017 DOI: /NEJMoa Romosozumab or Alendronate for Fracture Preven/on in Women with Osteoporosis Kenneth G. Saag, M.D., Jeffrey Petersen, M.D., Maria Luisa Brandi, M.D., Andrew C. Karaplis, M.D., Ph.D., Mažas Lorentzon, M.D., Ph.D., Thierry Thomas, M.D., Ph.D., Judy Maddox, D.O., Michelle Fan, Ph.D., Paul D. Meisner, Pharm.D., and Andreas Grauer, M.D.

67 Ανεπιθύμητες ενέργειες

The new england journal of medicine September 11, 2017 DOI: 10.1056/NEJMoa1708322 Romosozumab or Alendronate for Fracture Preven/on in Women with Osteoporosis Kenneth G. Saag, M.D., Jeffrey Petersen, M.

68 The new england journal of medicine September 11, 2017 DOI: /NEJMoa Romosozumab or Alendronate for Fracture Preven/on in Women with Osteoporosis Kenneth G. Saag, M.D., Jeffrey Petersen, M.D., Maria Luisa Brandi, M.D., Andrew C. Karaplis, M.D., Ph.D., Mažas Lorentzon, M.D., Ph.D., Thierry Thomas, M.D., Ph.D., Judy Maddox, D.O., Michelle Fan, Ph.D., Paul D. Meisner, Pharm.D., and Andreas Grauer, M.D.

69 Jul 21, 2016 Jul 16, 2017 Amgen and UCB Submit Biologics License Application for Romosozumab to the FDA Amgen and UCB Receive Complete Response Letter from U.S. FDA for Evenity (romosozumab) BLA The orig inal submission included data from the pivotal Phase 3 placebo - controlled FRAME study of postmenopausal women with osteoporosis. With the availability of data from the Phase 3 active-comparator ARCH study, the Agency has asked that the efficacy and safety data from the study be integrated into the application. The resubmission will also include the efficacy and safety data from the BRIDGE study, the Phase 3 trial evaluating Evenity in men with osteoporosis, which has also been requested. This request will be addressed in the form of a resubmission, which is an extension of the current review.

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Supplementary appendix

Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Langdahl BL, Libanati C, Crittenden DB, et