Investigational New Drug for Alzheimer’s Scheduled for First
Study in Humans--Vanderbilt Scientists Take
Investigational Drug Product From Bench To Clinical Trials in Humans
Newswise, February 13, 2017 — Vanderbilt University scientists
have received notification from the U.S. Food and Drug Administration (FDA)
that testing in humans may proceed for an investigational new drug after more
than 10 years of research by scientists at Vanderbilt University and Vanderbilt
University Medical Center.
It is relatively uncharted territory for an academic drug discovery group to
take a molecule from the laboratory setting to the clinical trials stage.
“The movement to the clinical phase of the research is the
result of tireless colleagues reaching across disciplines in pursuit of the
shared goal of hoping to someday improve the lives of individuals with
Alzheimer’s disease and possibly other brain disorders, such as schizophrenia,”
Provost and Vice Chancellor for Academic Affairs Susan R. Wente, Ph.D. said.
“This work exactly illustrates the critical role that basic
science conducted in partnership with a world-class medical center can play in
advancing knowledge in an attempt to fight a devastating disease.”
For Alzheimer’s disease, the aim is for the investigational drug to target
major pathologies of the disease and selectively activate a key receptor in the
brain. The Vanderbilt researchers believe that the current standard of care for
Alzheimer’s disease, cholinesterase inhibitors, has a different mechanism of
action.
They are hoping to establish through future clinical testing
that the molecule is broadly effective across a number of cognitive and
neuropsychiatric disorders, including schizophrenia.
“This is the first instance I am aware of where an academic drug discovery
group moved a molecule designed to hopefully treat a chronic brain disorder all
the way from early discovery to human trials without there being, at some point
along the way, a pharmaceutical partner,” said P. Jeffrey Conn, Ph.D., Lee E.
Limbird Professor of Pharmacology in the Vanderbilt University School of
Medicine and director of the Vanderbilt Center for Neuroscience Drug Discovery
(VCNDD).
“And that really is crossing what people refer to all of the time as the
‘Valley of Death,’ where good research discoveries have a hard time moving into
the clinical testing phase due to lack of funding,” he said.
“Importantly, at this early stage, the FDA has only granted
permission to assess potential safety of this investigational new drug in
healthy volunteers” said Conn.
“We cannot predict the outcome, but if these studies are
successful in demonstrating that the investigational drug can be safely
administered to humans, this would pave the way to allow filing of additional
applications with the FDA to seek permission to advance to testing for efficacy
in improving cognitive function in patients suffering from Alzheimer’s disease,
and possibly schizophrenia or other brain disorders.
“While we cannot predict the outcome of any future safety or
efficacy studies, this decision by FDA allowing clinical research to begin
represents a major milestone in allowing us to hopefully provide answers to
those critical questions in the future,” Conn said.
VCNDD Co-Director Craig W. Lindsley, Ph.D., director of Medicinal Chemistry and
William K. Warren, Jr. Professor of Medicine, said phase I testing will assess
drug safety and tolerability in healthy volunteer participants, a process that
could take a year.
If successful, the phase II and III studies would include
efficacy assessments in patients with Alzheimer’s disease and could take 3-5
years to complete.
“We are hoping to address what we see as an unmet medical need,” Lindsley said.
“For Alzheimer’s patients, the standard of care for
symptomatic treatment remains cholinesterase inhibitors, which are 25 years old
at this point. There hasn’t been any real scientific advancement in this field
in a long time.”
Lindsley and Conn credit The William K. Warren Foundation for its philanthropic
investments along the way to make clinical trials for this investigational drug
a reality.
“One of the most challenging things about doing this in an academic environment
is funding,” Lindsley said.
“Every step requires funding and if there is a delay or break
in funding, then everything sits idle and potentially innovative approaches for
patient care do not advance.”
“Being matched with the Warrens happened serendipitously. They have invested so
much in our programs, and it is wonderful to show them progress on their
investments,” he said.
“Without the financial support from the Warrens, this
investigational drug would not be poised to enter human clinical trials.”
The William K. Warren Foundation Chief Executive Officer John-Kelly Warren said
he is gratified that FDA has allowed for the investigational drug to proceed to
testing in human beings.
“Although this is an important sequential milestone, the only milestone that
matters to us is the hope that one day we will learn that this investigational
new drug has positively and safely changed the life of a patient suffering from
a brain disorder such as schizophrenia or Alzheimer’s disease,” Warren
said.
“That day will warrant a celebration felt in the heavens. Until then, we are
prepared to support the VCNDD research team until they can deliver the
necessary results,” he said.
A NIH National Cooperative Drug Discovery/Development grant funded the early
basic science and discovery of this investigational drug and the Alzheimer’s
Drug Discovery Foundation and Harrington Discovery Institute helped support
some of the key toxicity studies that FDA required, Conn said.
“The investigational new drug has the potential to improve cognitive functions
with fewer unwanted side effects.
“This could someday be an important advance for the treatment
of cognitive deficits in psychiatric disorders and Alzheimer’s disease,” said
Joshua Gordon, M.D., Ph.D., director of the National Institute of Mental
Health, which co-funded the research.
Conn and Lindsley said Vanderbilt’s “team science” approach included
contributions from the director of Translational Pharmacology and Development
for the VCNDD and Assistant Professor Carrie K. Jones, Ph.D., who coordinated
the IND drafting, submission, and subsequent development into Phase I, director
of Molecular Pharmacology for the VCNDD and Research Associate Professor of
Pharmacology Colleen Niswender, Ph.D., for the molecular pharmacology; Research
Assistant Professor of Pharmacology Jerri Rook, Ph.D., for the behavioral
studies; and Research Assistant Professor of Pharmacology Thomas Bridges,
Ph.D., and Research Assistant Professor of Pharmacology Anna Blobaum, Ph.D.,
for drug metabolism and pharmacokinetic profiling.
Paul Newhouse, M.D., director of the Center for Cognitive Medicine at VUMC and
Jim Turner Professor in Cognitive Disorders, is expected to lead the upcoming
clinical study funded in part by the Alzheimer’s Association and Alzheimer’s
Drug Discovery Foundation.
