The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer’s disease patients

Matthew E. Kennedy; Andrew W. Stamford; Xia Chen; Kathleen Cox; Jared N. Cumming; Marissa F. Dockendorf; Michael Egan; Larry Ereshefsky; Robert A. Hodgson; Lynn A. Hyde; Stanford Jhee; Huub J. Kleijn; Reshma Kuvelkar; Wei Li; Britta A. Mattson; Hong Mei; John Palcza; Jack D. Scott; Michael Tanen; Matthew D. Troyer; Jack L. Tseng; Julie A. Stone; Eric M. Parker; Mark S. Forman

doi:10.1126/scitranslmed.aad9704

Research ArticleAlzheimer’s Disease

The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer’s disease patients

Matthew E. Kennedy¹,*,
Andrew W. Stamford²,*,
Xia Chen¹,
Kathleen Cox³,
Jared N. Cumming²,
Marissa F. Dockendorf³,
Michael Egan⁴,
Larry Ereshefsky⁵,
Robert A. Hodgson¹,†,
Lynn A. Hyde¹,
Stanford Jhee⁵,
Huub J. Kleijn³,‡,
Reshma Kuvelkar¹,
Wei Li²,
Britta A. Mattson⁶,
Hong Mei³,
John Palcza⁷,
Jack D. Scott²,
Michael Tanen⁸,
Matthew D. Troyer⁹,§,
Jack L. Tseng⁹,¶,
Julie A. Stone³,
Eric M. Parker¹,* and
Mark S. Forman⁹,*

¹Department of Neuroscience, Merck Research Laboratories, Kenilworth, NJ 07033, USA.
²Department of Global Chemistry, Merck Research Laboratories, Kenilworth, NJ 07033, USA.
³Department of Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories, Kenilworth, NJ 07033, USA.
⁴Department of Clinical Research, Merck Research Laboratories, Kenilworth, NJ 07033, USA.
⁵PAREXEL, Glendale, CA 91206, USA.
⁶Department of Safety Assessment, Merck Research Laboratories, West Point, PA 19446, USA.
⁷Department of Biostatistics, Merck Research Laboratories, Kenilworth, NJ 07033, USA.
⁸Translational Biomarkers Department, Merck Research Laboratories, Kenilworth, NJ 07033, USA.
⁹Department of Translational Medicine, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

↵*Corresponding author. Email: matthew.kennedy{at}merck.com (M.E.K.); andy.stamford1{at}gmail.com (A.W.S.); ericmcparker{at}comcast.net (E.M.P.); mark.forman{at}merck.com (M.S.F.)

↵† Present address: Charles River Laboratories, Wilmington, MA 01887, USA.
↵‡ Present address: Quantitative Solutions, Oss, Netherlands.
↵§ Present address: Medivation, San Francisco, CA 94105, USA.
↵¶ Present address: Purdue Pharma, Stamford, CT 06901, USA.

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Science Translational Medicine 02 Nov 2016:
Vol. 8, Issue 363, pp. 363ra150
DOI: 10.1126/scitranslmed.aad9704

Matthew E. Kennedy

1Department of Neuroscience, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

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For correspondence: matthew.kennedy@merck.com andy.stamford1@gmail.com ericmcparker@comcast.net mark.forman@merck.com

Andrew W. Stamford

2Department of Global Chemistry, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

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For correspondence: matthew.kennedy@merck.com andy.stamford1@gmail.com ericmcparker@comcast.net mark.forman@merck.com

Xia Chen

1Department of Neuroscience, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

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Kathleen Cox

3Department of Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

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Jared N. Cumming

2Department of Global Chemistry, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

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Marissa F. Dockendorf

3Department of Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

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Michael Egan

4Department of Clinical Research, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

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Larry Ereshefsky

5PAREXEL, Glendale, CA 91206, USA.

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Robert A. Hodgson

1Department of Neuroscience, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

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Lynn A. Hyde

1Department of Neuroscience, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

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Stanford Jhee

5PAREXEL, Glendale, CA 91206, USA.

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Huub J. Kleijn

3Department of Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

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Reshma Kuvelkar

1Department of Neuroscience, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

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Wei Li

2Department of Global Chemistry, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

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Britta A. Mattson

6Department of Safety Assessment, Merck Research Laboratories, West Point, PA 19446, USA.

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Hong Mei

3Department of Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

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John Palcza

7Department of Biostatistics, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

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Jack D. Scott

2Department of Global Chemistry, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

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Michael Tanen

8Translational Biomarkers Department, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

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Matthew D. Troyer

9Department of Translational Medicine, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

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Jack L. Tseng

9Department of Translational Medicine, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

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Julie A. Stone

3Department of Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

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Eric M. Parker

1Department of Neuroscience, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

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For correspondence: matthew.kennedy@merck.com andy.stamford1@gmail.com ericmcparker@comcast.net mark.forman@merck.com

Mark S. Forman

9Department of Translational Medicine, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

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For correspondence: matthew.kennedy@merck.com andy.stamford1@gmail.com ericmcparker@comcast.net mark.forman@merck.com

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The BACE1 inhibitor verubecestat safely reduces β-amyloid deposition in rats, monkeys, healthy human subjects, and patients with Alzheimer’s disease.

The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer’s disease patients

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