Zevra Therapeutics, Inc. (NasdaqGS: ZVRA) (Zevra, or the Company),
a rare disease therapeutics company, today announced that final
positive results 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) were presented in a poster at SLEEP
2024, the 38th annual joint meeting of the American Academy of
Sleep Medicine and the Sleep Research Society, held in Houston, TX,
June 1-5, 2024. In addition, a second poster describing the
pharmacokinetics of SDX when administered in the morning and at
night was also presented.
“We are encouraged by the positive results of
the Phase 2 clinical trial, which serve as further support of
KP1077 as a strong candidate to treat patients struggling with
idiopathic hypersomnia,” said Adrian Quartel, MD, FFPM, Chief
Medical Officer of Zevra. “We believe that KP1077 has great
potential to provide a differentiated treatment option for patients
underserved by currently available therapies.”
This proof-of-concept study was designed to
demonstrate safety and tolerability and was not powered to
demonstrate statistical significance. However, the trial included
several important secondary and exploratory endpoints, such as
change in Epworth Sleepiness Scale (ESS) total score, 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. These data gathered from the secondary endpoints will
help inform the study design for a potential Phase 3 clinical trial
of KP1077.
“The results of the Phase 2 clinical trial
support the safety and tolerability of KP1077 as measured by the
primary endpoint of the study,” stated Christopher Drake, PhD,
FAASM, DBSM, Principal Investigator of the study. “The clinically
meaningful impact for both the safety and efficacy were well
demonstrated by patients showing significant improvements in IH
symptom severity such as sleep inertia, excessive daytime
sleepiness (EDS), and patient-reported IH-specific outcomes.”
Key Takeaways from Phase 2 Clinical
Trial of KP1077 for Idiopathic Hypersomnia:
- KP1077 was well
tolerated at all dose levels evaluated in the trial, including the
highest dose of 320 mg daily, regardless of the dosing regimen:
once daily (QD) or twice daily (BID).
- Adverse events
(AEs) were similar to other methylphenidate products
- Most common AEs
included insomnia, headache, anxiety, decreased appetite, and
nausea
- Most AEs
occurred during the titration period, were mild, and did not lead
to early discontinuation
- KP1077 produced
clinically meaningful improvements in EDS as assessed by change
from baseline in the ESS during both the 5-week open-label (OL)
titration period which was maintained during the 2-week
double-blind withdrawal period for both dosing regimens.
- Mean total ESS
scores decreased by approximately 9 points after 5 weeks of OL
treatment.
- At the end of 7
weeks of treatment, patients administered KP1077 showed clinically
meaningful benefits in change from baseline for the ESS, IHSS,
SIVAS, and Brain Fog Scale (BFS):
- Mean total ESS score decreased by
9.4 (QD) and 8.8 (BID)
- Mean total IHSS score decreased by
16.1 (QD) and 12.3 (BID)
- Mean SIVAS score decreased by 25.9
(QD) and 17.2 (BID)
- Mean total BFS symptom score
decreased by 23.8 (QD) and 22.3 (BID)
- The study
successfully fulfilled the objectives of providing key information
for the design of a pivotal efficacy trial, and the results of the
secondary efficacy endpoints were supportive of initiating a Phase
3 trial of KP1077.
Separately, the pharmacokinetics of morning and
nighttime dose of KP1077 was studied. These data are also being
presented in a poster at SLEEP 2024.
Key Takeaways from Pharmacokinetics of
Morning and Nighttime Doses of KP1077
Based on the Phase 2 trial results, the Company
believes that:
- Peak exposure of SDX-derived d-MPH
after a nighttime dose of SDX occurs during the next morning
leading to higher exposure at awakening compared to a morning
dose.
- The delay in
exposure is likely due to a longer intestinal transit time and
lower intestinal activity during the nighttime sleeping hours.
- The delay in
exposure supports nighttime dosing of SDX in patients with IH who
suffer from EDS and sleep inertia (difficulty waking up in the
morning).
The results from each study were discussed
during two poster presentations in Hall A3, Poster Presentation
Session P-13:
- Title: Safety and
Efficacy of KP1077 in a Phase 2, Double-blind, Randomized Trial in
Patients with Idiopathic HypersomniaDate/Time:
June 3, 2024, 10 a.m. to 11:45 a.m. CDT
- Title:
Pharmacokinetics of Morning and Nighttime Doses of KP1077, an
Investigational Treatment for Idiopathic
HypersomniaDate/Time: June 3, 2024, 10 a.m. to
11:45 a.m. CDT
Representatives from Zevra Therapeutics are also
available during exhibit hours at Booth #1421 for additional
discussion. Zevra proudly supports the Hypersomnia Foundation’s
mission to raise awareness, educate, and uplift the voices of those
living with idiopathic hypersomnia and was proud to participate in
the inaugural Idiopathic Hypersomnia Day (IH Day) on June 1, 2024.
IH Day, held in Houston during the Hypersomnia Foundation’s
BeyondSleepy Conference, served as the kickoff to Idiopathic
Hypersomnia Awareness Week, which runs through June 7, 2024.
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 5-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
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), and by the European
Commission, for the treatment of IH. 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. In addition, KP1077 has intellectual
property protection through 2037 and potentially beyond.
About Zevra TherapeuticsZevra
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.
Expanded access programs are made available by
Zevra Therapeutics and its affiliates and are subject to the
Company's Expanded Access Program (EAP) policy as published on its
website. Participation in these programs is subject to the laws and
regulations of each jurisdiction under which each respective
program is operated. Eligibility for participation in any such
program is at the treating physician's discretion.
For more information, please visit
www.zevra.com or follow us on X (formerly Twitter) and
LinkedIn.
About American Academy of Sleep
MedicineEstablished in 1975 as the Association of Sleep
Disorders Centers, the American Academy of Sleep Medicine (AASM) is
the only professional society dedicated exclusively to the medical
subspecialty of sleep medicine. As the leading voice in the sleep
field, the AASM sets standards and promotes excellence in sleep
medicine health care, education, and research. The AASM has a
combined membership of 11,000 accredited member sleep centers and
individual members, including physicians, scientists, and other
health care professionals.
About the Sleep Research
SocietyThe Sleep Research Society (SRS) is an organization
for scientific investigators who educate and research sleep and
circadian science. The SRS serves its members and the field of
sleep research through training and education, and by providing
forums for the collaboration and the exchange of ideas.
Cautionary Note 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 initiation, timing, design,
or results of any clinical trials or readouts, the potential
benefits of any of our products or product candidates for any
specific disease indication or at any dosage, and upcoming events
or Zevra’s participation at such events. 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, 2023, Zevra’s quarterly
report for the three months ended March 31, 2024, 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) 754-2545
nochsner@zevra.com
Russo Partners Contacts Adanna G. Alexander,
Ph.D. +1 (646) 942-5603 adanna.alexander@russopartnersllc.com
Ignacio Guerrero-Ros, Ph.D. +1 (646) 942-5604
ignacio.guerrero-ros@russopartnersllc.com
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