Karuna Doses First Subject in Tolerability Proof-of-Concept Study

BOSTON–(BUSINESS WIRE)–Karuna
Pharmaceuticals, a company focused on targeting muscarinic receptors
for the treatment of central nervous system (CNS) disorders including
schizophrenia and Alzheimer’s disease, today announced the dosing of the
first subject in a tolerability proof-of-concept study of its
proprietary lead product KarXT (xanomeline
plus trospium chloride). The study, which
will be conducted in up to 70 healthy individuals, aims to evaluate the
tolerability of KarXT compared to xanomeline alone.
Exclusively licensed to Karuna, xanomeline is a novel, muscarinic
acetylcholine receptor agonist that has demonstrated robust efficacy in
treating schizophrenia and psychosis in Alzheimer’s disease; however, it
has also been associated with tolerability issues that have hindered its
development. In a double-blind, placebo-controlled, monotherapy study in
people with schizophrenia, a statistically significant, 24-point
reduction over placebo was observed on the Positive and Negative
Syndrome Scale (PANSS), a standard tool used to measure symptom severity
in people with schizophrenia. By selectively targeting muscarinic
receptors in the CNS with the KarXT approach, Karuna aims to reduce the
peripheral cholinergic side effects previously seen with xanomeline
alone.
“In clinical studies, xanomeline has shown robust efficacy in people
with schizophrenia and in people with Alzheimer’s disease, demonstrating
the immense potential of targeting the M1/M4 muscarinic acetylcholine
receptors; however, the muscarinic field has been stymied by
tolerability concerns caused by activation of muscarinic receptors in
peripheral tissues,” said Andrew Miller, Ph.D., Karuna’s Chief Executive
Officer. “By combining xanomeline with trospium chloride, we aim to
unlock the therapeutic potential of M1/M4 agonists and address the
significant unmet need in treating these disorders.”
The randomized, double-blind, multiple-dose study will dose up to 70
healthy volunteers aged 18 to 60 for in-clinic treatment over the course
of nine days. Following a two-day run-in period with trospium alone,
subjects will receive xanomeline with either trospium chloride or
placebo. Top-line results are expected by the end of 2016.
About Karuna
Karuna is a clinical-stage drug development
company targeting muscarinic receptors for the treatment of central
nervous system (CNS) disorders. Karuna’s lead program, KarXT,
is a product candidate consisting of xanomeline,
a novel muscarinic acetylcholine receptor agonist that has demonstrated
efficacy in placebo-controlled human trials in schizophrenia and
Alzheimer’s disease, and trospium
chloride, an FDA-approved and well-established muscarinic receptor
antagonist that has been shown not to enter the CNS.
Schizophrenia is a severe and chronic mental health disorder that
affects more than 21 million people worldwide. The disease is
characterized by profound disruptions in thinking, affecting language,
perception and the sense of self, and it typically includes psychotic
episodes. Antipsychotics are the mainstay therapy for the treatment of
schizophrenia; however, significant unmet needs remain due to the
limited efficacy and potential serious side effects associated with
current antipsychotic medications.
Alzheimer’s disease is a chronic, progressive, neurodegenerative
disorder characterized by loss of memory and other important mental
functions. The type, severity, sequence and progression of mental
changes vary widely, and it represents an enormous burden on victims of
the disease and their families. Alzheimer’s is the most common form of
dementia in people over the age of 65, and it is estimated to affect
more than 5 million Americans. It is the sixth leading cause of death in
the United States, and there is currently no cure.
Karuna’s Board of Directors includes Ben Shapiro, M.D., former Executive
Vice President of Research for Merck & PureTech Health Non-Executive
Director; Edmund Harrigan, M.D., former Senior Vice President for
Worldwide Safety and Regulatory, Head of Worldwide Business Development
at Pfizer; and Atul Pande, M.D., Former Senior Vice President, Head of
Neuroscience and Senior Advisor, Pharmaceutical R&D at GlaxoSmithKline &
PureTech Health Senior Advisor. Karuna’s Chief Clinical Advisor is Alan
Breier, M.D., the former Chief Medical Officer at Eli Lilly. Karuna has
a worldwide exclusive license for xanomeline and has a patent portfolio
more broadly covering selective muscarinic targeting enabled by the
KarXT approach. For more information, visit www.karunapharma.com.
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