Etranacogene dezaparvovec (AMT-061 phase 2b): Normal/near normal FIX activity and bleed cessation in hemophilia B

Annette Von Drygalski; Adam Giermasz; Giancarlo Castaman; Nigel S. Key; Susan Lattimore; Frank W.G. Leebeek; Wolfgang Miesbach; Michael Recht; Alison Long; Robert Gut; Eileen K. Sawyer; Steven W. Pipe

doi:10.1182/bloodadvances.2019000811

Etranacogene dezaparvovec (AMT-061 phase 2b): Normal/near normal FIX activity and bleed cessation in hemophilia B

Annette Von Drygalski, Adam Giermasz, Giancarlo Castaman, Nigel S. Key, Susan Lattimore, Frank W.G. Leebeek, Wolfgang Miesbach, Michael Recht, Alison Long, Robert Gut, Eileen K. Sawyer, Steven W. Pipe

Pediatrics

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Original language	English (US)
Pages (from-to)	3241-3247
Number of pages	7
Journal	Blood Advances
Volume	3
Issue number	21
DOIs	https://doi.org/10.1182/bloodadvances.2019000811
State	Published - Nov 12 2019

ASJC Scopus subject areas

Hematology

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10.1182/bloodadvances.2019000811

Cite this

Drygalski, A. V., Giermasz, A., Castaman, G., Key, N. S., Lattimore, S., Leebeek, F. W. G., Miesbach, W., Recht, M., Long, A., Gut, R., Sawyer, E. K., & Pipe, S. W. (2019). Etranacogene dezaparvovec (AMT-061 phase 2b): Normal/near normal FIX activity and bleed cessation in hemophilia B. Blood Advances, 3(21), 3241-3247. https://doi.org/10.1182/bloodadvances.2019000811

Etranacogene dezaparvovec (AMT-061 phase 2b) : Normal/near normal FIX activity and bleed cessation in hemophilia B. / Drygalski, Annette Von; Giermasz, Adam; Castaman, Giancarlo; Key, Nigel S.; Lattimore, Susan; Leebeek, Frank W.G.; Miesbach, Wolfgang; Recht, Michael; Long, Alison; Gut, Robert; Sawyer, Eileen K.; Pipe, Steven W.

In: Blood Advances, Vol. 3, No. 21, 12.11.2019, p. 3241-3247.

Research output: Contribution to journal › Article › peer-review

Drygalski, Annette Von ; Giermasz, Adam ; Castaman, Giancarlo ; Key, Nigel S. ; Lattimore, Susan ; Leebeek, Frank W.G. ; Miesbach, Wolfgang ; Recht, Michael ; Long, Alison ; Gut, Robert ; Sawyer, Eileen K. ; Pipe, Steven W. / Etranacogene dezaparvovec (AMT-061 phase 2b) : Normal/near normal FIX activity and bleed cessation in hemophilia B. In: Blood Advances. 2019 ; Vol. 3, No. 21. pp. 3241-3247.

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title = "Etranacogene dezaparvovec (AMT-061 phase 2b): Normal/near normal FIX activity and bleed cessation in hemophilia B",

author = "Drygalski, {Annette Von} and Adam Giermasz and Giancarlo Castaman and Key, {Nigel S.} and Susan Lattimore and Leebeek, {Frank W.G.} and Wolfgang Miesbach and Michael Recht and Alison Long and Robert Gut and Sawyer, {Eileen K.} and Pipe, {Steven W.}",

note = "Funding Information: To retain the favorable characteristics of AMT-060 but provide FIX activity in a range predicted to completely eliminate bleeding and preserve joint function, the AMT-060 FIX transgene cassette was modified with a single amino acid change (R338L) previously shown to result in a highly active FIX protein (etranacogene dezaparvo-vec [AMT-061]).5,16,17 This naturally occurring variant, termed FIX Padua, has been reported to have a FIX activity-to-protein ratio of ;6 in animal models and between 5 and 10 in humans.5,16,18 The change to human FIX (hFIX) Padua was expected to result in higher levels of FIX activity with the same dose of vector and thereby further alleviate the bleed risk and need for exogenous therapy for etranacogene dezaparvovec compared with AMT-060. The switch of transgene was not expected to influence other previously reported safety characteristics of AAV5-wt FIX at the established dose of 2 ⨯ 1013 genome copies (gc) per kilogram.2 This phase 2b study was proposed by uniQure and supported by the US Food and Drug Administration and the European Medicines Agency to Funding Information: Conflict-of-interest disclosure: A.V.D. has received honoraria for participating in scientific advisory board panels, consulting, and speaking engagements from uniQure, Biomarin, Novo Nordisk, Bayer, Bioverativ/Sanofi, Spark Therapeutics, HEMA Biologics, Pfizer, CSL Behring, Sanofi, Shire, and Takeda; receives research funding from Bioverativ/Sanofi, and Pfizer; and is a cofounder and a member of the Board of Directors of Hematherix LLC., a biotech company that is developing superFVa therapy for bleeding complications. A.G. received honoraria for advisory board meetings from uniQure, Bioverativ, Genentech/Roche, Biomarin, and Novo Nordisk; and speaker{\textquoteright}s fees from Bioverativ, Genentech/Roche, and Alexion. G.C. participated in the Advisory Board of uniQure; received fees as a speaker or to participate in Advisory Boards from Bayer, Shire/Takeda, CSL Behring, Sobi, Novo Nordisk, Roche, Werfen, Ablynx, and Kedrion; and received research grants directly to his institution from Pfizer, Sobi, and CSL Behring. N.S.K. has received consultant fees from uniQure for participation on the Steering Committee for this study. S.L. reports consultant fees from uniQure during the conduct of the study. F.W.G.L. has received unrestricted research grants from CSL Behring and Shire/Takeda; is a consultant for UniQure, Shire, and Novo Nordisk, of which the fees go to the university; and is a Data and Safety Monitoring Board member for a study by Roche. W.M. has received consultant fees from UniQure. B.V. during the conduct of the study; grants and personal fees from Novo Nordisk; and personal fees from Bayer, Shire, Biotest, Pfizer, Octapharma, LFB, CSL Behring, SOBI, Biogen, and BPL outside the submitted work. M.R. has received research support for his institution from Bioverativ, Genentech, Novo Nordisk, and Shire; reports consultant fees from Bio-verativ, CSL Behring, Genentech, Kedrion, Novo Nordisk, Pfizer, Shire, and uniQure; and is the immediate past chair, Board of Directors, American Thrombosis and Hemostasis Network. A.L., R.G., and E.K.S. are uniQure employees. S.W.P. has served as a consultant to ApcinteX, Bayer, Biomarin, Bioverativ, Catalyst Biosciences, CSL Behring, HEMA Biologics, Freeline, Novo Nordisk, Pfizer, Roche/Genentech, Sanofi, Shire, Spark Therapeutics, and uniQure.",

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doi = "10.1182/bloodadvances.2019000811",

language = "English (US)",

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pages = "3241--3247",

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T1 - Etranacogene dezaparvovec (AMT-061 phase 2b)

T2 - Normal/near normal FIX activity and bleed cessation in hemophilia B

AU - Drygalski, Annette Von

AU - Giermasz, Adam

AU - Castaman, Giancarlo

AU - Key, Nigel S.

AU - Lattimore, Susan

AU - Leebeek, Frank W.G.

AU - Miesbach, Wolfgang

AU - Recht, Michael

AU - Long, Alison

AU - Gut, Robert

AU - Sawyer, Eileen K.

AU - Pipe, Steven W.

N1 - Funding Information: To retain the favorable characteristics of AMT-060 but provide FIX activity in a range predicted to completely eliminate bleeding and preserve joint function, the AMT-060 FIX transgene cassette was modified with a single amino acid change (R338L) previously shown to result in a highly active FIX protein (etranacogene dezaparvo-vec [AMT-061]).5,16,17 This naturally occurring variant, termed FIX Padua, has been reported to have a FIX activity-to-protein ratio of ;6 in animal models and between 5 and 10 in humans.5,16,18 The change to human FIX (hFIX) Padua was expected to result in higher levels of FIX activity with the same dose of vector and thereby further alleviate the bleed risk and need for exogenous therapy for etranacogene dezaparvovec compared with AMT-060. The switch of transgene was not expected to influence other previously reported safety characteristics of AAV5-wt FIX at the established dose of 2 ⨯ 1013 genome copies (gc) per kilogram.2 This phase 2b study was proposed by uniQure and supported by the US Food and Drug Administration and the European Medicines Agency to Funding Information: Conflict-of-interest disclosure: A.V.D. has received honoraria for participating in scientific advisory board panels, consulting, and speaking engagements from uniQure, Biomarin, Novo Nordisk, Bayer, Bioverativ/Sanofi, Spark Therapeutics, HEMA Biologics, Pfizer, CSL Behring, Sanofi, Shire, and Takeda; receives research funding from Bioverativ/Sanofi, and Pfizer; and is a cofounder and a member of the Board of Directors of Hematherix LLC., a biotech company that is developing superFVa therapy for bleeding complications. A.G. received honoraria for advisory board meetings from uniQure, Bioverativ, Genentech/Roche, Biomarin, and Novo Nordisk; and speaker’s fees from Bioverativ, Genentech/Roche, and Alexion. G.C. participated in the Advisory Board of uniQure; received fees as a speaker or to participate in Advisory Boards from Bayer, Shire/Takeda, CSL Behring, Sobi, Novo Nordisk, Roche, Werfen, Ablynx, and Kedrion; and received research grants directly to his institution from Pfizer, Sobi, and CSL Behring. N.S.K. has received consultant fees from uniQure for participation on the Steering Committee for this study. S.L. reports consultant fees from uniQure during the conduct of the study. F.W.G.L. has received unrestricted research grants from CSL Behring and Shire/Takeda; is a consultant for UniQure, Shire, and Novo Nordisk, of which the fees go to the university; and is a Data and Safety Monitoring Board member for a study by Roche. W.M. has received consultant fees from UniQure. B.V. during the conduct of the study; grants and personal fees from Novo Nordisk; and personal fees from Bayer, Shire, Biotest, Pfizer, Octapharma, LFB, CSL Behring, SOBI, Biogen, and BPL outside the submitted work. M.R. has received research support for his institution from Bioverativ, Genentech, Novo Nordisk, and Shire; reports consultant fees from Bio-verativ, CSL Behring, Genentech, Kedrion, Novo Nordisk, Pfizer, Shire, and uniQure; and is the immediate past chair, Board of Directors, American Thrombosis and Hemostasis Network. A.L., R.G., and E.K.S. are uniQure employees. S.W.P. has served as a consultant to ApcinteX, Bayer, Biomarin, Bioverativ, Catalyst Biosciences, CSL Behring, HEMA Biologics, Freeline, Novo Nordisk, Pfizer, Roche/Genentech, Sanofi, Shire, Spark Therapeutics, and uniQure.

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