KarXT Demonstrated Statistically Significant
and Clinically Meaningful Improvement in Total PANSS Score at All
Time Points Over Five Weeks and was Well-Tolerated Compared to
Placebo
Improvement in Total PANSS Score at Five
Weeks was 11.6 Points Compared to Placebo (p<0.0001)
No Evidence of Somnolence, Extrapyramidal
Side Effects or Weight Gain Relative to Placebo
Data Support Advancing KarXT to Phase 3 and
Continued Development in Other CNS Disorders
Conference Call and Webcast to Take Place
Today at 8:30 a.m. EST
Karuna Therapeutics, Inc. (Nasdaq: KRTX), a clinical-stage
biopharmaceutical company committed to developing novel therapies
with the potential to transform the lives of people with disabling
and potentially fatal neuropsychiatric disorders and pain, today
announced results from its Phase 2 clinical trial of KarXT for the
treatment of acute psychosis in patients with schizophrenia. In the
clinical trial, KarXT demonstrated a statistically significant and
clinically meaningful 11.6 point mean reduction in total Positive
and Negative Syndrome Scale (PANSS) score compared to placebo
(p<0.0001) and also demonstrated good overall tolerability. A
statistically significant reduction in the secondary endpoints of
PANSS-Positive and PANSS-Negative scores were also observed
(p<0.001).
KarXT was well tolerated in the Phase 2 trial, with similar
discontinuation rates between KarXT (20%) and placebo (21%). The
number of discontinuations due to treatment emergent adverse events
(AEs) were equal in the KarXT and placebo arms (N=2 in each
group).
KarXT is an oral coformulation of xanomeline (a novel muscarinic
receptor agonist) and trospium (a muscarinic receptor antagonist)
designed to treat psychosis and related symptoms through
preferential stimulation of muscarinic receptors in the central
nervous system (CNS). This combination has the potential to be a
new option for treating the difficult symptoms of debilitating CNS
disorders, such as schizophrenia, without subjecting patients to
the problematic side effects associated with current antipsychotic
standard of care therapies.
“The results of the Phase 2 trial are impressive and encouraging
because they indicate that KarXT, if approved, could represent a
game-changing therapeutic advance in the treatment of patients with
schizophrenia,” said Jeffrey Lieberman, M.D., professor and
chairman of the Department of Psychiatry, Columbia University,
College of Physicians and Surgeons and a member of Karuna’s
scientific advisory board. “The effectiveness of antipsychotics has
been limited by the frequent and serious side effects of first- and
second-generation drugs which are difficult for many patients to
tolerate, are potentially harmful, and lead to high rates of
discontinuation and relapse. In addition to its novel mechanism of
action, KarXT could be a new therapeutic option that has the
potential to offer robust efficacy devoid of weight gain, metabolic
effects and extrapyramidal side effects.”
In the clinical trial, patients demonstrated a clinically
meaningful and statistically significant 11.6 point mean reduction
over placebo in total PANSS score, the trial’s primary efficacy
endpoint. The magnitude of the improvement with KarXT compares
favorably to meta-analyses of published clinicals trials of
currently approved antipsychotic medicines which reported an
average difference of nine to ten points in PANSS score versus
placebo. Historically, changes as small as five points have
supported the approval of current antipsychotics.
Overall, KarXT was well tolerated in the clinical trial, with
similar discontinuation rates of patients on KarXT, 20%, and
placebo, 21%. The number of discontinuations due to treatment
emergent AEs were equal in the KarXT and placebo arms (N=2 in each
group). The overall AE rate of patients on KarXT was 54% vs. 43% on
placebo, with the most common AEs being constipation, nausea, dry
mouth, dyspepsia, and vomiting. The tolerability of KarXT was also
reflected in the trial’s high rate of dose escalation. In the
trial, 91% of KarXT treated patients escalated to the increased
dose which was similar to the escalation rate with placebo.
Occurrences of somnolence, weight gain, and extrapyramidal symptoms
were also similar to placebo. One serious adverse event (SAE) was
experienced in the drug treatment arm, in which the patient
discontinued treatment and subsequently sought hospital care for
worsening psychosis, meeting the regulatory definition of an
SAE.
“The schizophrenia treatment landscape has remained rather
stagnant for decades with therapeutic options relying on
discoveries dating back to the 1950s,” said Steve Paul, M.D., chief
executive officer, president, and chairman of Karuna. “KarXT and
its novel muscarinic receptor mechanism of action represent the
potential to become a true advancement in how schizophrenia is
treated, allowing patients relief from their debilitating psychotic
symptoms without experiencing some of the very troubling side
effects associated with current treatments.”
Muscarinic acetylcholine receptors emerged in the 1990s as a
promising alternative target to dopamine-receptor based treatments
for treating psychosis, but adverse side effects limited their
development as a therapeutic option. It is believed that these side
effects were the result of the stimulation of muscarinic receptors
in peripheral tissues. Karuna addressed this issue by combining
xanomeline, a novel muscarinic receptor agonist that preferentially
stimulates M1 and M4 muscarinic receptors, with trospium, an
approved muscarinic receptor antagonist that does not measurably
cross the blood-brain barrier, confining its effects to peripheral
tissues. The resulting therapeutic, known as KarXT, was designed to
activate muscarinic receptors in the CNS while avoiding the side
effects associated with activating muscarinic receptors in
peripheral tissues.
“We are extremely pleased with these results, as the 11.6-point
PANSS score separation from placebo far exceeded the five-point
minimum improvement that has historically supported approval of
current antipsychotics,” said Stephen Brannan, M.D., chief medical
officer of Karuna. “With this information, and following our
anticipated end-of-Phase 2 meeting with the FDA in the second
quarter of 2020, we will work to initiate a Phase 3 clinical trial
of KarXT in patients with schizophrenia by the end of 2020. We also
plan to further analyze these results to better understand the
potential of KarXT in patients with schizophrenia experiencing
negative and cognitive symptoms, and to explore other CNS disorders
that could benefit from this approach, such as psychosis in
Alzheimer’s disease as well as the management of pain.”
About the Trial
The Phase 2, randomized, double-blind, placebo-controlled,
inpatient trial enrolled 182 adult patients, age 18 to 60, who had
been diagnosed with DSM-5 schizophrenia and were experiencing acute
psychosis. Patients were washed-out of antipsychotic medicines and
randomized 1:1 to receive either KarXT or placebo for five weeks.
The primary outcome measure of the trial was the change from
baseline on the total PANSS score on KarXT vs. placebo treatment at
week five.
KarXT was dosed as xanomeline 50 mg/trospium 20 mg twice a day
for two days and then increased to xanomeline 100 mg/trospium 20 mg
starting on day three. Beginning on day eight, if KarXT was well
tolerated, an option was given to escalate the dose of KarXT to
xanomeline 125 mg/trospium 30 mg twice a day. If a patient
escalated to the highest dose, the dose could be decreased back to
xanomeline 100 mg/trospium 20 mg twice per day, based on
tolerability, if needed. No dose changes were allowed during the
last two weeks of the trial.
About Schizophrenia
Schizophrenia is a chronic, disabling disorder typically
diagnosed in late teenage years or early adulthood. Characterized
by recurring episodes of psychosis requiring long-term treatment
with antipsychotic drugs in most patients, it affects more than 21
million people worldwide and 2.7 million Americans (0.5% - 1.0% of
U.S. population).
At least one-third of patients with schizophrenia fail to
respond to current treatments, with 74% of patients discontinuing
within 18 months of initiation. People with schizophrenia have a
10- to 15-year reduction in life expectancy and struggle to
maintain meaningful interpersonal relationships. The World Health
Organization ranks psychosis as the third-most disabling medical
condition in the world.
Conference Call and Webcast Information
Karuna will hold a webcast and conference call this morning at
8:30 a.m. EST to provide results from its Phase 2 clinical trial of
KarXT for the treatment of acute psychosis in patients with
schizophrenia. The dial-in numbers are 1-855-548-1216 for domestic
callers and 1-409-216-6318 for international callers. The
conference ID number for the live call will be 9498519. A live
webcast of the conference call will also be available on the
investor relations page of the Karuna Therapeutics corporate
website at www.karunatx.com. After the live webcast, the event will
remain archived on the Karuna Therapeutics website for three
months.
About Karuna
Karuna is a clinical-stage biopharmaceutical company committed
to developing and delivering first-in-class therapies with the
potential to transform the lives of people with CNS disorders –
which remain among the most disabling and potentially fatal
disorders worldwide. Galvanized by the understanding that today’s
neuropsychiatric and pain management patients deserve better,
Karuna’s mission is to harness the untapped potential of the
brain’s complex biology in pursuit of novel therapeutic pathways
that will advance the standard of care. For more information,
please visit karunatx.com.
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version on businesswire.com: https://www.businesswire.com/news/home/20191118005243/en/
Investor Contact: Chris Brinzey Westwicke, an ICR Company
+1 339 970-2843 chris.brinzey@westwicke.com
Media Contact: Jenn Gordon GlobalHealthPR +1 202 587-2580
jgordon@globalhealthpr.com
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