Zevra Therapeutics, Inc. (NasdaqGS: ZVRA) (Zevra, or the
Company) a rare disease therapeutics company, today announced
top-line data from its placebo-controlled, double-blind Phase 2
clinical trial (NCT05668754) evaluating the safety and tolerability
of KP1077 (serdexmethylphenidate, or SDX) in patients with
idiopathic hypersomnia (IH). This proof-of-concept study was not
powered to demonstrate statistical significance. The
data gathered for several secondary and exploratory endpoints,
including the Epworth Sleepiness Scale (ESS), Idiopathic
Hypersomnia Severity Scale (IHSS) and Sleep Inertia Visual Analog
Scale (SIVAS) will inform the Phase 3 study design.
“Zevra’s Phase 2 trial evaluating KP1077 as a
treatment for IH demonstrated clinically meaningful impact and
encouraging outcomes on both clinical safety and efficacy,” stated
Christopher Drake, PhD, FAASM, DBSM, Principal Investigator of the
study. “During the open-label dose titration period,
patients showed robust improvements in IH symptom severity,
including excessive daytime sleepiness that were maintained during
the double-blind withdrawal period. At the end of the study,
patients randomized into the KP1077 treatment group also
demonstrated improvements in patient reported IH specific outcomes.
We look forward to presenting the final results of the Phase 2
trial at the upcoming SLEEP 2024 annual meeting.”
“We’re thankful to the patients in the Phase 2
clinical trial for their participation in advancing the
investigational treatment, KP1077, for IH,” said Neil McFarlane,
Chief Executive Officer of Zevra. “We believe KP1077 has strong
potential to alleviate the immense burden of key IH symptoms,
including excessive daytime sleepiness, sleep inertia and brain
fog, and could provide a differentiated treatment option for
patients underserved by currently available therapies. We would
also like to thank our IH-focused patient advocacy group partners
and supporters for making this clinical trial possible. Their
partnership in raising awareness for this study and supporting
trial enrollment has been crucial for its success.”
The positive top-line results of the Phase 2
trial support the safety and tolerability of KP1077 as measured by
the primary endpoint of the study. The study also successfully
fulfilled the objectives of providing key information for the
design of a potentially pivotal efficacy trial, and the results of
the secondary efficacy endpoints were supportive of initiating a
Phase 3 trial of KP1077.
KP1077 was shown to be well-tolerated at all
dose levels evaluated in the trial, including the highest dose of
320 mg daily, regardless of dosing regimen (once or twice daily).
The most common adverse events were insomnia, headache, anxiety,
nausea, and decreased appetite. Due to its unique pharmacokinetic
profile, adverse events were mostly mild in severity despite higher
overall exposure levels when compared to both immediate and
long-acting methylphenidate products currently used off-label for
the treatment of IH.
Topline results of the Phase 2 study
include:
- KP1077 produced
clinically meaningful improvement in excessive daytime sleepiness
(EDS), as assessed by change from baseline in the Epworth
Sleepiness Scale (ESS), that was maintained during both the
five-week open-label titration period and throughout the 2-week
double-blind withdrawal period for both dosing regimens.
- Patients
administered KP1077 showed benefits in change from baseline for the
IH Severity Scale (IHSS), Sleep Inertia Visual Analog Scale (SIVAS)
and Brain Fog severity Scale (BFS) at the end of the open-label
dose titration, and at the end of the double-blind withdrawal
period.
- The results from
the completed Phase 2 trial provide key information for the design
of a potentially pivotal Phase 3 trial of KP1077 in patients with
IH.
The Company plans to request an end-of-Phase 2
(EOP2) meeting with the U.S. Food and Drug Administration to seek
guidance on the Phase 3 clinical trial design.
About the KP1077 Phase 2
Trial
The Phase 2 clinical trial was a double-blind,
placebo-controlled, randomized-withdrawal, dose-optimizing,
multi-center study that evaluated the safety and efficacy of KP1077
for the treatment of IH. Part 1 of the trial consisted of a
five-week open-label dose titration phase during which patients
were optimized to one of four doses of KP1077 (80, 160, 240, or 320
mg/day). Part 2 of the trial entailed a two-week randomized,
double-blind, withdrawal phase, during which two-thirds of the
trial participants continued to receive their optimized dose while
the remaining one-third received placebo. Participants were
assigned into two evenly divided cohorts. The first cohort received
a single daily dose just before bedtime, and the second cohort
received half the daily dose shortly after awakening and the second
half prior to bedtime. Zevra enrolled 66 adult patients with IH in
24 centers in the U.S into the open-label titration phase of the
study and 50 of those patients continued into the double-blind
phase.
The primary endpoint was the safety and
tolerability of KP1077. The major secondary efficacy endpoint was
the change in Epworth Sleepiness Scale (ESS) total score.
Additional secondary endpoints included the IH Severity Scale
(IHSS), the Sleep Inertia Visual Analog Scale (SIVAS), and a new
scale to assess the symptoms and severity of brain fog.
About Idiopathic Hypersomnia
(IH)
Idiopathic hypersomnia (IH) is a rare sleep
disorder characterized by excessive daytime sleepiness (EDS).
Patients with IH experience daytime lapses into sleep, or an
irrepressible need to sleep that persists even with adequate or
prolonged nighttime sleep. Additionally, those with IH have extreme
difficulty waking, otherwise known as sleep inertia, severe brain
fog, and often fall asleep unintentionally or at inappropriate
times. These symptoms of IH often lead to further, even more
debilitating problems such as memory lapses, difficulty maintaining
focus, and depression.
It is estimated, based on claims data, that
approximately 37,000 patients in the United States are currently
diagnosed with IH, although the total patient population may be
much larger due to some patients who have not yet been diagnosed,
have been misdiagnosed, or are not currently seeking treatment.
About KP1077
KP1077 (serdexmethylphenidate or SDX) is Zevra’s
proprietary prodrug of d-methylphenidate (d-MPH) and its sole
active pharmaceutical ingredient (API). KP1077 has been granted
Orphan Drug Designation by the U.S. Food and Drug
Administration (FDA) for the treatment of IH, and
the U.S. Drug Enforcement Agency (DEA) has classified
SDX, the sole API in KP1077, as a Schedule IV controlled substance
based on evidence suggesting SDX has a lower potential for abuse
when compared to d-MPH, a Schedule II controlled substance.
About Zevra Therapeutics
Zevra Therapeutics is a rare disease company
combining science, data, and patient needs to create
transformational therapies for diseases with limited or no
treatment options. Our mission is to bring life-changing
therapeutics to people living with rare diseases. With unique,
data-driven development and commercialization strategies, the
Company is overcoming complex drug development challenges to make
new therapies available to the rare disease community.
For more information, please
visit www.zevra.com or follow us on X (formerly
Twitter) and LinkedIn.
Caution Concerning Forward-Looking
Statements
This press release may contain forward-looking
statements within the meaning of the Private Securities Litigation
Reform Act of 1995. Forward-looking statements include all
statements that do not relate solely to historical or current
facts, including without limitation statements regarding the
promise and potential impact of our preclinical or clinical trial
data; the design, initiation, timing and results of any clinical
trials or readouts; interpretations of trial data outcomes on
clinical safety and efficacy; Zevra’s reports regarding or
presentation of trial data, including at conferences, or the timing
thereof; the promise and potential impact of any of our products or
product candidates for any specific disease indication or at any
dosage; Zevra’s plans to request an end-of-Phase 2 (EOP2) meeting;
the potential launch or commercialization of any of product
candidates or products, and our strategic and product development
objectives, including with respect to becoming a leading,
commercially focused rare disease company. Forward-looking
statements are based on information currently available to Zevra
and its current plans or expectations. They are subject to several
known and unknown uncertainties, risks, and other important factors
that may cause our actual results, performance, or achievements to
be materially different from any future results, performance, or
achievements expressed or implied by the forward-looking
statements. These and other important factors are described in
detail in the “Risk Factors” section of Zevra’s Annual Report on
Form 10-K for the year ended December 31, 2022, as updated in
Zevra’s Quarterly Report on Form 10-Q for the quarter ended
September 30, 2023, and Zevra’s other filings with the Securities
and Exchange Commission. While we may elect to update such
forward-looking statements at some point in the future, except as
required by law, we disclaim any obligation to do so, even if
subsequent events cause our views to change. Although we believe
the expectations reflected in such forward-looking statements are
reasonable, we cannot assure that such expectations will prove
correct. These forward-looking statements should not be relied upon
as representing our views as of any date after the date of this
press release. Zevra Contact
Nichol Ochsner+1 (732) 754-2545nochsner@zevra.com
Russo Partners Contacts
Adanna G. Alexander, Ph.D.+1 (646)
942-5603adanna.alexander@russopartnersllc.com
Ignacio Guerrero-Ros, Ph.D.+1 (646)
942-5604ignacio.guerrero-ros@russopartnersllc.com
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