Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) today announced that the
company’s partner, Karuna Therapeutics, Inc. (NASDAQ: KRTX),
reported positive topline results from its Phase 3 EMERGENT-3 trial
evaluating the efficacy, safety, and tolerability of its lead
investigational therapy, KarXT (xanomeline-trospium) in adults with
schizophrenia. The trial met its primary endpoint, with KarXT
demonstrating a statistically significant and clinically meaningful
8.4-point reduction in Positive and Negative Syndrome Scale (PANSS)
total score compared to placebo (-20.6 KarXT vs. -12.2 placebo;
p<0.0001) at Week 5 (Cohen’s d effect size of 0.60). Consistent
with prior trials, KarXT demonstrated an early and sustained
statistically significant reduction of symptoms from Week 2
(p<0.05) through the end of the trial as assessed by PANSS total
score.
KarXT also demonstrated reductions in positive and negative
symptoms of schizophrenia as measured by PANSS positive, PANSS
negative, and PANSS negative Marder factor subscales – secondary
endpoints in the trial. KarXT demonstrated a clinically meaningful
and statistically significant 3.5-point reduction in PANSS positive
subscale compared to placebo at Week 5 (-7.1 KarXT vs. -3.6
placebo; p<0.0001). While not meeting the threshold for
statistical significance at Week 5, KarXT did demonstrate a
statistically significant reduction in PANSS negative subscale and
PANSS negative Marder factor subscale compared to placebo at Week 4
(p<0.05).
KarXT was generally well tolerated, with a side effect profile
substantially consistent with prior trials of KarXT. The overall
discontinuation rate in the trial was 33% (37% KarXT vs. 29%
placebo). The overall treatment emergent adverse event (TEAE) rates
for KarXT and placebo were 70% and 50%, respectively.
Discontinuation rates related to TEAEs were similar between
treatment arms (6% KarXT vs. 5% placebo), consistent with the
EMERGENT-1 and EMERGENT-2 trials. The only serious TEAE reported in
the KarXT arm was related to gastroesophageal reflux disease (acid
reflux) and deemed not to be related to study drug. There were no
serious TEAEs reported in the placebo group. The most common KarXT
TEAEs (>5%) were nausea, dyspepsia, vomiting, constipation,
headache, hypertension, diarrhea, and insomnia, which were all
rated mild or moderate in severity. There were no discontinuations
due to TEAEs of hypertension. Mean blood pressure measures were
similar between KarXT and placebo, and no syncopal events were
observed. Similar to prior trials, an increase in heart rate was
associated with KarXT treatment and decreased in magnitude by the
end of the trial. Measures of weight gain, somnolence, and
extrapyramidal symptoms of KarXT were similar to placebo,
consistent with prior trials of KarXT in schizophrenia.
The NDA submission for KarXT to the FDA in schizophrenia will
incorporate the efficacy and safety data from the three
placebo-controlled registrational trials, EMERGENT-1, EMERGENT-2,
and EMERGENT-3, in addition to long-term safety data from the
ongoing EMERGENT-4 and EMERGENT-5 trials. Karuna is on track to
submit an NDA to the FDA in mid-2023, with a potential launch in
the second half of 2024 in the United States, if approved.
Zai Lab is on track to initiate a bridging study for the
treatment of patients with schizophrenia in China in mid-2023.
About the EMERGENT-3 TrialThe Phase 3
EMERGENT-3 trial is a double-blind, placebo-controlled, five-week,
inpatient trial evaluating the efficacy, safety, and tolerability
of our lead investigational therapy, KarXT, compared to placebo in
adults with schizophrenia in the United States and Ukraine. The
primary endpoint was change from baseline in Positive and Negative
Syndrome Scale (PANSS) total score, a scale for measuring
schizophrenia symptom severity, of KarXT compared to placebo at
Week 5. Prespecified secondary endpoints included change from
baseline in PANSS positive, PANSS negative and PANSS negative
Marder factor subscale of KarXT compared to placebo at Week 5.
A total of 256 adults (between the ages of 18-65 years) with
schizophrenia enrolled in the trial. Enrolled patients had a
confirmed diagnosis of schizophrenia and were experiencing symptoms
of psychosis at the time of enrollment.
Patients were randomized 1:1 to receive either a flexible dose
of KarXT or placebo two times a day (BID) for five weeks. On Days
1-2, patients received a dose of 50/20 KarXT (50mg xanomeline/20mg
trospium) BID or matching placebo. On Day 3, patients escalated to
a dose of 100/20 BID, and on Day 8, patients had the option to
increase to 125/30 BID based on tolerability. In the trial, 79% of
patients on KarXT compared to 91% on placebo titrated to the
highest dose level (125/30 BID).
About KarXTKarXT (xanomeline-trospium) is an
oral, investigational M1/M4-preferring muscarinic agonist in
development for the treatment of psychiatric and neurological
conditions, including schizophrenia and psychosis in Alzheimer’s
disease. KarXT is the first potential medicine of its kind with a
truly new and unique dual mechanism of action. Unlike current
therapies, KarXT does not rely on the dopaminergic or serotonergic
pathways, and it is designed to harness the therapeutic potential
of xanomeline while managing peripheral side effects through
trospium. This approach has the potential to provide a
differentiated therapy, and, if approved, to beneficially impact
the lives of millions of people with serious mental illness.
Zai Lab has an exclusive license agreement with Karuna
Therapeutics for the development, manufacturing, and
commercialization of KarXT in Greater China, including mainland
China (“China”), Hong Kong, Macau, and Taiwan (collectively
“Greater China”).
About SchizophreniaSchizophrenia is a
persistent and often disabling mental illness affecting how a
person thinks, feels, and behaves. It is characterized by positive
symptoms (hallucinations and delusions), negative symptoms
(difficulty enjoying life and withdrawal from others), and
cognitive impairment (deficits in memory, concentration, and
decision-making) – all of which can severely impact functioning,
with only 10% of people gainfully employed and many struggling to
meet adult milestones such as living independently. The life
expectancy of people living with schizophrenia is reduced by 10-20
years compared to the general population. Schizophrenia affects
more than 21 million people worldwide and is most commonly treated
with antipsychotics. Unfortunately, many people with schizophrenia
continue to experience limited efficacy or problematic side effects
while on antipsychotic therapy, and approximately 75% of patients
discontinue medication before 18 months. When schizophrenia
treatment is discontinued, it can lead to impacts on health
including relapse, hospitalization, and longer time to
remission.
More than 8 million people in China are living with
schizophrenia, yet fewer than half are receiving treatment, and
even fewer are obtaining adequate symptom improvement using the
current treatment of antipsychotics. Like patients globally, there
is a significant need for more effective therapies with improved
safety to treat serious psychiatric conditions for patients with
schizophrenia in Greater China.
About Zai LabZai Lab (NASDAQ: ZLAB; HKEX: 9688)
is an innovative, research-based, commercial-stage
biopharmaceutical company based in China and the United States
focused on bringing transformative medicines for oncology,
autoimmune disorders, infectious diseases, and neurological
disorders to patients in China and around the world. Our goal is to
leverage our competencies and resources to positively impact human
health worldwide.
For additional information about Zai Lab, please visit
www.zailaboratory.com or follow us at
www.twitter.com/ZaiLab_Global.
Forward-Looking StatementsThis press release
contains forward-looking statements relating to our collaboration
with Karuna Therapeutics, Inc., including specifically the results
from the pivotal Phase 3 EMERGENT-3 trial of KarXT in schizophrenia
and the potential to effectively treat patients in Greater China
with schizophrenia that are suffering from serious psychiatric
conditions. All statements, other than statements of historical
fact, included in this press release are forward-looking
statements, and can be identified by words such as “aim,”
“anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,”
“goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will,”
“would,” and other similar expressions. Such statements constitute
forward-looking statements within the meaning of the Private
Securities Litigation Reform Act of 1995. Forward-looking
statements are not guarantees or assurances of future performance.
Forward-looking statements are based on our expectations and
assumptions as of the date of this press release and are subject to
inherent uncertainties, risks, and changes in circumstances that
may differ materially from those contemplated by the
forward-looking statements. You should not place undue reliance on
these forward-looking statements. Actual results may differ
materially from those indicated by forward-looking statements as a
result of various important factors, including but not limited to
(1) the results of our clinical and pre-clinical development of our
product candidates, (2) the content and timing of decisions made by
the relevant regulatory authorities regarding regulatory approvals
of our product candidates, (3) the effects of the novel coronavirus
(COVID-19) pandemic, including any government actions or lockdown
measures taken in response, on our business and general economic,
regulatory, and political conditions, (4) risks related to doing
business in China, and (5) other factors identified in our most
recent annual and quarterly reports and in other reports we have
filed with the U.S. Securities and Exchange Commission. We
anticipate that subsequent events and developments will cause our
expectations and assumptions to change, and we undertake no
obligation to update or revise any forward-looking statements,
whether as a result of new information, future events, or
otherwise, except as may be required by law. These forward-looking
statements should not be relied upon as representing our views as
of any date subsequent to the date of this press release.
Our SEC filings can be found on our website at
www.zailaboratory.com and on the SEC’s website at www.sec.gov.
For more information, please contact:
Investor Relations: Lina Zhang+86 136 8257
6943lina.zhang@zailaboratory.com
Media: Jennifer Chang / Xiaoyu Chen+1 (917)
446-3140 / +86 185 0015 5011jennifer.chang@zailaboratory.com /
xiaoyu.chen@zailaboratory.com
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