PLYMOUTH MEETING, Pa.,
Oct. 13, 2023 /PRNewswire/ -- Harmony
Biosciences Holdings, Inc. ("Harmony" or the "Company") (Nasdaq:
HRMY), a pharmaceutical company dedicated to developing and
commercializing innovative therapies for patients with rare
neurological diseases, today announced topline results from the
INTUNE study in patients with idiopathic hypersomnia (IH).
Kumar Budur, M.D., Chief Medical
Officer at Harmony Biosciences said, "We are very encouraged by the
magnitude of the response seen in the initial open-label treatment
period, where 83% of patients completing this phase responded with
an average 9.4 point improvement in the Epworth Sleepiness Scale
(ESS). Equally encouraging is the number of patients, almost 90%,
electing to continue into the long-term extension study, allowing
us to generate additional safety and efficacy data in this patient
population. Positive trends in other important outcomes like sleep
inertia add to the totality of evidence that pitolisant has a
clinical benefit for patients with IH."
The INTUNE study was a Phase 3 placebo-controlled, double-blind,
randomized withdrawal study. Approximately 83% of patients who
completed the 8-week open-label treatment period with pitolisant
were responders (as defined by a decrease on the ESS of ≥3 points)
and experienced a robust clinical response, with an average ESS
change from baseline of – 9.4 points. A positive trend favoring
pitolisant was observed during the 4-week double-blind randomized
withdrawal period, however no statistically significant difference
was observed between pitolisant and placebo groups on ESS, the
primary endpoint. Positive trends favoring pitolisant were also
observed across additional prespecified endpoints including the
IHSS, which approached statistical significance, as well as on the
SlQ. Further data analyses are being conducted. Approximately 88%
of patients in the study continued into a 12-month long-term
extension study, which is ongoing. The safety and tolerability
profile of pitolisant in adult patients with idiopathic hypersomnia
was consistent with the established safety profile and no new
safety signals were observed.
Dr. Budur added, "We are grateful to the patients, family
members and clinicians who participated in the INTUNE study. We
remain committed to the IH patient community and understand their
strong desire for a non-scheduled treatment option for IH.
Following a thorough review of the full data set, we will work
closely with the FDA to discuss next steps and a path forward for
pitolisant in IH."
Pitolisant is marketed as WAKIX® in the U.S. for the
treatment of EDS or cataplexy in adult patients with narcolepsy.
Pitolisant is not approved for IH and is currently being evaluated
as an investigational agent in adult patients with IH.
Conference Call Today at 8:30 a.m.
ET
We are hosting a conference call and webcast today
at 8:30 a.m. Eastern Time to discuss
the topline data from the Phase 3 INTUNE study. The live and replay
webcast of the call will be available on the investor relations
page of our website at https://ir.harmonybiosciences.com/. To
participate in the live call by phone, dial (800) 245-3047
(domestic) or +1 (203) 518-9765 (international), and reference
passcode HRMY1013.
About the INTUNE Study
The INTUNE study is a
placebo-controlled, double-blind, randomized withdrawal Phase 3
registrational trial conducted in adult patients with IH at 52
clinical trial sites across the U.S. A total of 213 patients were
enrolled and dosed in the study, of which 139 were randomized. The
primary objective was to evaluate the safety and efficacy of
pitolisant compared with placebo in treating EDS. The secondary
objectives were to assess the impact of pitolisant on other
important symptoms of IH, such as sleep inertia, daytime
functioning, and cognitive performance. The INTUNE study had two
periods: (1) an 8-week open-label period consisting of 3 weeks of
dose titration, 3 weeks of dose optimization and 2 weeks of stable
dose; followed by (2) a 4-week double-blind randomized withdrawal
(DBRW) period. During the open-label period, all patients were
treated with pitolisant. Treatment responders entered the DBRW
phase where half of them continued to receive stable dose
pitolisant whereas the other half received placebo. All efficacy
assessments were administered during the DBRW phase and analyzed to
compare the difference between the pitolisant group and the placebo
group from the end of stable dose period to the end of the 4-week
DBRW phase.
About Idiopathic Hypersomnia
Idiopathic Hypersomnia
(IH) is a rare and chronic neurological disease that is
characterized by excessive daytime sleepiness (EDS) despite
sufficient or even long sleep time. People living with IH
experience significant EDS along with the symptoms of sleep inertia
(prolonged difficulty waking up from sleep) and 'brain fog'
(impaired cognition, attention, and alertness). The cause of IH is
unknown, but it is likely due to alterations in areas of the brain
that stabilize states of sleep and wakefulness. IH is one of the
central disorders of hypersomnolence and, like narcolepsy, is a
debilitating sleep disorder that can result in significant
disruption in daily functioning. Approximately 80,000 people in
the U.S. are believed to be affected by IH, with 40,000
currently having been diagnosed. IH is a condition with high unmet
medical need.
About WAKIX® (pitolisant) Tablets
WAKIX, a
first-in-class medication, is approved by the U.S. Food and Drug
Administration for the treatment of excessive daytime sleepiness or
cataplexy in adult patients with narcolepsy and has been
commercially available in the U.S. since Q4 2019. It was granted
orphan drug designation for the treatment of narcolepsy in 2010,
and breakthrough therapy designation for the treatment of cataplexy
in 2018. WAKIX is a selective histamine 3 (H₃) receptor
antagonist/inverse agonist. The mechanism of action of WAKIX is
unclear; however, its efficacy could be mediated through its
activity at H₃ receptors, thereby increasing the synthesis and
release of histamine, a wake promoting neurotransmitter. WAKIX was
designed and developed by Bioprojet (France). Harmony has an exclusive license from
Bioprojet to develop, manufacture and commercialize pitolisant in
the United States.
Indications and Usage
WAKIX is indicated for the
treatment of excessive daytime sleepiness or cataplexy in adult
patients with narcolepsy.
Important Safety Information
Contraindications
WAKIX is contraindicated in patients
with known hypersensitivity to pitolisant or any component of the
formulation. Anaphylaxis has been reported. WAKIX is also
contraindicated in patients with severe hepatic impairment.
Warnings and Precautions
WAKIX prolongs the QT
interval; avoid use of WAKIX in patients with known QT prolongation
or in combination with other drugs known to prolong the QT
interval. Avoid use in patients with a history of cardiac
arrhythmias, as well as other circumstances that may increase the
risk of the occurrence of torsade de pointes or sudden death,
including symptomatic bradycardia, hypokalemia or hypomagnesemia,
and the presence of congenital prolongation of the QT interval.
The risk of QT prolongation may be greater in patients with
hepatic or renal impairment due to higher concentrations of
pitolisant; monitor these patients for increased QTc. Dosage
modification is recommended in patients with moderate hepatic
impairment and moderate or severe renal impairment (see full
prescribing information). WAKIX is not recommended in patients with
end-stage renal disease (ESRD).
Adverse Reactions
In the placebo-controlled clinical
trials conducted in patients with narcolepsy with or without
cataplexy, the most common adverse reactions (≥5% and at least
twice placebo) for WAKIX were insomnia (6%), nausea (6%), and
anxiety (5%). Other adverse reactions that occurred at ≥2% and more
frequently than in patients treated with placebo included headache,
upper respiratory tract infection, musculoskeletal pain, heart rate
increased, hallucinations, irritability, abdominal pain, sleep
disturbance, decreased appetite, cataplexy, dry mouth, and
rash.
Drug Interactions
Concomitant administration of WAKIX
with strong CYP2D6 inhibitors increases pitolisant exposure by
2.2-fold. Reduce the dose of WAKIX by half.
Concomitant use of WAKIX with strong CYP3A4 inducers decreases
exposure of pitolisant by 50%. Dosage adjustments may be required
(see full prescribing information).
H1 receptor antagonists that cross the blood-brain barrier may
reduce the effectiveness of WAKIX. Patients should avoid centrally
acting H1 receptor antagonists.
WAKIX is a borderline/weak inducer of CYP3A4. Therefore, reduced
effectiveness of sensitive CYP3A4 substrates may occur when used
concomitantly with WAKIX. The effectiveness of hormonal
contraceptives may be reduced when used with WAKIX and
effectiveness may be reduced for 21 days after discontinuation of
therapy.
Use in Specific Populations
WAKIX may reduce the
effectiveness of hormonal contraceptives. Patients using hormonal
contraception should be advised to use an alternative non-hormonal
contraceptive method during treatment with WAKIX and for at least
21 days after discontinuing treatment.
There is a pregnancy exposure registry that monitors pregnancy
outcomes in women who are exposed to WAKIX during pregnancy.
Patients should be encouraged to enroll in the WAKIX pregnancy
registry if they become pregnant. To enroll or obtain information
from the registry, patients can call 1-800-833-7460. The safety and
effectiveness of WAKIX have not been established in patients less
than 18 years of age.
WAKIX is extensively metabolized by the liver. WAKIX is
contraindicated in patients with severe hepatic impairment. Dosage
adjustment is required in patients with moderate hepatic
impairment.
WAKIX is not recommended in patients with end-stage renal
disease. Dosage adjustment of WAKIX is recommended in patients with
moderate or severe renal impairment.
Dosage reduction is recommended in patients known to be poor
CYP2D6 metabolizers; these patients have higher concentrations of
WAKIX than normal CYP2D6 metabolizers.
Please see the Full Prescribing Information for WAKIX
for more information.
To report suspected adverse reactions, contact Harmony
Biosciences at 1-800-833-7460 or the FDA at 1-800-FDA-1088
or www.fda.gov/medwatch.
About Harmony Biosciences
At Harmony Biosciences, we
specialize in developing and delivering treatments for rare
neurological diseases that others often overlook. We believe that
where empathy and innovation meet, a better life can begin for
people living with neurological diseases. Established by Paragon
Biosciences, LLC, in 2017 and headquartered in Plymouth Meeting, PA, our team of experts from
a wide variety of disciplines and experiences is driven by our
shared conviction that innovative science translates into
therapeutic possibilities for our patients, who are at the heart of
everything we do. For more information, please
visit www.harmonybiosciences.com.
Forward Looking Statement
This press release contains
forward-looking statements within the meaning of the Private
Securities Litigation Reform Act of 1995. All statements contained
in this press release that do not relate to matters of historical
fact should be considered forward-looking statements, including
statements regarding our product WAKIX. These statements are
neither promises nor guarantees, but involve known and unknown
risks, uncertainties 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, including,
but not limited to, the following: our commercialization efforts
and strategy for WAKIX; the rate and degree of market acceptance
and clinical utility of WAKIX, pitolisant in additional
indications, if approved, and any other product candidates we may
develop or acquire, if approved; our research and development
plans, including our development activities with Bioprojet, and
plans to explore the therapeutic potential of pitolisant in
additional indications; our ongoing and planned clinical trials;
the availability of favorable insurance coverage and reimbursement
for WAKIX; the timing of and our ability to obtain regulatory
approvals for pitolisant for other indications as well as any of
our product candidates, including those we are developing with
Bioprojet; our failure to achieve the potential benefits of the
2022 LCA with Bioprojet; our estimates regarding expenses, future
revenue, capital requirements and needs for additional financing;
our ability to identify additional products or product candidates
with significant commercial potential that are consistent with our
commercial objectives; our commercialization, marketing and
manufacturing capabilities and strategy; significant competition in
our industry; our intellectual property position; loss or
retirement of key members of management; failure to successfully
execute our growth strategy, including any delays in our planned
future growth; our failure to maintain effective internal controls;
the impact of government laws and regulations; volatility and
fluctuations in the price of our common stock; the significant
costs and required management time as a result of operating as a
public company; the fact that the price of Harmony's common stock
may be volatile and fluctuate substantially; statements related to
our intended share repurchases and repurchase timeframe and the
significant costs and required management time as a result of
operating as a public company. These and other important factors
discussed under the caption "Risk Factors" in our Annual Report on
Form 10-K filed with the Securities and Exchange Commission (the
"SEC") on February 21, 2023, and our
other filings with the SEC could cause actual results to differ
materially from those indicated by the forward-looking statements
made in this press release. Any such forward-looking statements
represent management's estimates as of the date of this press
release. While we may elect to update such forward-looking
statements at some point in the future, we disclaim any obligation
to do so, even if subsequent events cause our views to change.
Harmony Biosciences Media Contact:
Cate McCanless
202-641-6086
cmccanless@harmonybiosciences.com
Harmony Biosciences Investor Contact:
Luis Sanay, CFA
445-235-8386
lsanay@harmonybiosciences.com
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