Xenon Pharmaceuticals Announces Topline Results from Phase 2 Proof-of-Concept X-NOVA Clinical Trial of XEN1101 in Major Depressive Disorder (MDD)
27 November 2023 - 11:00PM
Xenon Pharmaceuticals Inc. (Nasdaq:XENE), a neurology-focused
biopharmaceutical company, today reported topline results from the
randomized, double-blind, placebo-controlled, Phase 2
proof-of-concept X-NOVA clinical trial, which evaluated the
clinical efficacy, safety, and tolerability of 10 mg and
20 mg of XEN1101 in 168 patients with moderate to severe major
depressive disorder, or MDD.
Summary of Efficacy Data
- The primary endpoint of the study
was a change in the Montgomery-Åsberg Depression Rating Scale, or
MADRS, at week 6. The mean reduction was 13.90 in the placebo
group, 15.61 in the XEN1101 10 mg group and 16.94 in the
XEN1101 20 mg group. A clear dose response and a clinically
meaningful, but not statistically significant, 3.04 difference
between placebo and the XEN1101 20 mg group (p=0.135) was
observed.
- Statistical significance was
achieved on the pre-specified endpoint of the Hamilton Depression
Rating Scale, or HAM-D17, at week 6 with a mean reduction of 10.18
in the placebo group and 13.26 in the XEN1101 20 mg group
(p=0.042).
- Statistical significance was
achieved on the key secondary endpoint of a change in the
Snaith-Hamilton Pleasure Scale, or SHAPS, measuring anhedonia at
week 6 with a reduction of 5.30 in the placebo group and 7.77 in
the XEN1101 20 mg group (p=0.046).
- Statistical significance was
achieved in MADRS at week 1 with a mean reduction of 4.88 in the
placebo group and 7.54 in the XEN1101 20 mg group (p=0.047)
demonstrating early onset of efficacy.
- Statistical significance was
achieved in reporting of at least minimally improved symptoms of
depression as assessed by physicians using the Clinical Global
Impression of Improvement (CGI-I) (p=0.004) in the XEN1101
20 mg group compared to placebo.
Summary of Safety and Tolerability Data
- XEN1101 was well tolerated with
similar rates of adverse events reported across all treatment
arms.
- The most commonly reported
treatment-emergent adverse events (TEAEs) in the XEN1101 20 mg
group included dizziness (17.9%), somnolence (10.7%), headache
(8.9%) and disturbance in attention (8.9%), as compared to the
placebo group which reported dizziness (7.3%), somnolence (1.8%),
headache (12.7%) and disturbance in attention (0%).
- Rates of discontinuation were
similar across all treatment arms and rates of discontinuation due
to TEAEs were low with three patients in the XEN1101 20 mg
group (5.4%), as compared to two patients in the placebo group
(3.6%).
- No serious adverse events (SAEs)
were reported in the two XEN1101 treatment groups and there were
two patients (3.6%) in the placebo group who experienced a
treatment-emergent SAE.
- XEN1101 was not associated with
clinically meaningful weight gain or sexual dysfunction.
Dr. Christopher Kenney, Xenon’s Chief Medical
Officer, stated, “We are encouraged by the data we have generated
with XEN1101 in this proof-of-concept study where we see clinically
meaningful, dose-dependent drug activity and early onset of
efficacy in depression. Importantly, XEN1101 was well tolerated in
this patient population, with a low incidence of treatment-emergent
adverse events, and no serious adverse events in either dose
group. These data also support our belief that XEN1101,
through its unique Kv7 mechanism of action, has the potential to
play an important role in addressing anhedonia, a common
co-morbidity in depression. Overall, there continues to be a strong
need for new treatment options for MDD, and we believe XEN1101 has
attractive qualities such as a novel mechanism, early onset of
action and an overall favorable tolerability and safety
profile.”
Ian Mortimer, Xenon’s President and Chief
Executive Officer stated, “Based on the totality of data from this
study, including clinically meaningful drug activity in depression
and anhedonia, we are actively exploring the future development of
XEN1101 in MDD and potentially other indications as we believe this
mechanism has potential broad applicability.”
Mr. Mortimer continued, “We believe that the
data from this study in depression further build upon XEN1101’s
compelling product profile in our ongoing Phase 3 development in
epilepsy. Data to date support XEN1101’s potential to combine many
key features important in treating epilepsy including compelling
efficacy in focal onset seizures, rapid efficacy as demonstrated by
statistically significant seizure reduction at week 1, a novel
mechanism of action with no titration required and other ease of
use attributes. We believe the new clinical data we have generated
through X-NOVA further support the potential of XEN1101 to have a
highly differentiated profile in the treatment of epilepsy given
the significant co-morbidity of depression in epilepsy patients. We
are excited to share the data generated in X-NOVA with
epileptologists and neurologists at the upcoming American Epilepsy
Society meeting in December.”
About the Phase 2 X-NOVA Clinical Trial in
MDD
The Phase 2 proof-of-concept X-NOVA clinical
trial evaluated the clinical efficacy, safety and tolerability of
10 mg or 20 mg of XEN1101 administered as monotherapy
with food in patients with MDD. Designed as a randomized,
double-blind, placebo-controlled, multicenter clinical study, the
primary objective was to assess the efficacy of XEN1101 compared to
placebo on improvement of depressive symptoms in subjects diagnosed
with moderate to severe MDD, using the MADRS score change through
week six. The X-NOVA study included a total of 168 randomized
subjects, 167 treated subjects in the safety population, and 164
subjects in the modified intent to treat population for the
efficacy analyses. The mean MADRS total scores at baseline were
34.2 for the XEN1101 10 mg group, 33.1 for the XEN1101
20 mg group and 34.5 for the placebo group, representing
patients with moderate to severe MDD. Other baseline demographic
characteristics were also similar across treatment arms.
Webcast/Conference Call
Information
Xenon will host a conference call and webcast today at 8:30 am
Eastern Time to discuss the Phase 2 X-NOVA results. You may view
the live webcast using this link, which can also be accessed on the
Investors section of the Xenon website. Participants who wish
to dial in to the live conference call should pre-register using
this link to obtain your unique PIN code. A replay of the webcast
will be available on the website approximately one hour after the
conclusion of the event and will be archived for approximately one
month.
About Xenon Pharmaceuticals
Inc.
Xenon Pharmaceuticals (NASDAQ:XENE) is a
clinical stage biopharmaceutical company committed to developing
innovative therapeutics to improve the lives of patients with
neurological disorders. We are advancing a novel product pipeline
of neurology therapies to address areas of high unmet medical need,
with a focus on epilepsy. For more information, please visit
www.xenon-pharma.com.
Safe Harbor Statement
This press release contains forward-looking
statements within the meaning of Section 27A of the Securities Act
of 1933, as amended, and Section 21E of the Securities Exchange Act
of 1934, as amended, and the Private Securities Litigation Reform
Act of 1995 and Canadian securities laws. These forward-looking
statements are not based on historical fact, and include statements
regarding the potential efficacy, safety profile, future
development plans, addressable market, regulatory success and
commercial potential of our product candidates; the efficacy of our
clinical trial designs; our ability to successfully develop and
achieve milestones in our XEN1101 and other development programs;
our ability to successfully develop and obtain regulatory approval
of XEN1101 and our other product candidates; and our intent to
explore future development of XEN1101 in MDD and potentially other
indications. These forward-looking statements are based on current
assumptions that involve risks, uncertainties and other factors
that may cause the actual results, events, or developments to be
materially different from those expressed or implied by such
forward-looking statements. These risks and uncertainties, many of
which are beyond our control, include, but are not limited to:
clinical trials may not demonstrate safety and efficacy of any of
our or our collaborators’ product candidates; promising results
from pre-clinical development activities or early clinical trial
results may not be replicated in later clinical trials; our
assumptions regarding our planned expenditures and sufficiency of
our cash to fund operations may be incorrect; our ongoing discovery
and pre-clinical efforts may not yield additional product
candidates; any of our or our collaborators’ product candidates,
including XEN1101, may fail in development, may not receive
required regulatory approvals, or may be delayed to a point where
they are not commercially viable; we may not achieve additional
milestones in our proprietary or partnered programs; regulatory
agencies may impose additional requirements or delay the initiation
of clinical trials; the impact of competition; the impact of
expanded product development and clinical activities on operating
expenses; the impact of new or changing laws and regulations; the
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obligation to update these forward-looking statements, and readers
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owner.
Investor/Media Contact:Jodi Regts Xenon
Pharmaceuticals Inc. Phone: 604.484.3353 Email:
investors@xenon-pharma.com
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