PLYMOUTH
MEETING, Pa., June 24,
2024 /PRNewswire/ -- Harmony Biosciences (Nasdaq:
HRMY) today announced that the U.S. Food and Drug Administration
(FDA) has approved its supplemental New Drug Application (sNDA) for
WAKIX® (pitolisant) tablets for the treatment of
excessive daytime sleepiness (EDS) in pediatric patients 6 years of
age and older with narcolepsy. The FDA separated the submission
into two sNDAs for administrative purposes to issue an approval for
the treatment of EDS and a complete response for the treatment of
cataplexy in pediatric patients (6 to <18 years of age) with
narcolepsy.
The FDA granted priority review of the sNDA based on a Phase 3
study conducted by Bioprojet, which evaluated the safety and
efficacy of pitolisant in patients ages 6 to under 18 years with
narcolepsy, with or without cataplexy. Based on the results of this
study, Bioprojet received approval from the European
Medicines Agency last year extending the indication for WAKIX
to include the treatment of narcolepsy in children ages 6 years of
age and older, with or without cataplexy.
"Following the FDA's decision to grant priority review, we are
very pleased with the Agency's timely review and approval of WAKIX
for pediatric narcolepsy patients with excessive daytime
sleepiness," said Jeffrey M. Dayno,
M.D., President and Chief
Executive Officer of Harmony Biosciences. "EDS is the primary
symptom experienced by all patients with narcolepsy and this
approval for WAKIX, as the first-and-only FDA-approved
non-scheduled treatment option for narcolepsy, makes this important
treatment option available to pediatric patients 6 years and older
living with narcolepsy."
WAKIX was first approved by the FDA in August 2019 for the treatment of EDS in adult
patients with narcolepsy, followed by FDA approval for the
treatment of cataplexy in adult patients with narcolepsy in
October 2020. A first-in-class
treatment with a novel mechanism of action, WAKIX functions as a
selective histamine 3 (H₃) receptor antagonist/inverse agonist that
is believed to target the histamine system to promote
wakefulness.
Dayno added, "The unique mechanism of action of WAKIX and its
non-scheduled status are especially important for a pediatric
population that has had limited treatment options, all of which are
controlled substances. The unique features of pitolisant present an
exciting opportunity, and we are currently working on the
next-generation formulations that could potentially offer
additional benefits to patients, such as greater efficacy and new
indications, extend the WAKIX franchise, and strengthen our
leadership position in the treatment of rare sleep disorders."
"We plan to discuss with the Agency a path forward for a
cataplexy indication in pediatric narcolepsy patients based on the
strength of the existing data from Bioprojet's Phase 3 trial," said
Kumar Budur, M.D., M.S., Chief
Medical and Scientific Officer of Harmony Biosciences. "We
appreciate the FDA's recognition of the unmet medical need in this
patient population and their approval of the EDS indication, making
WAKIX available to every appropriate pediatric patient 6 years and
older living with narcolepsy."
"As a parent of a son who was diagnosed with narcolepsy in
childhood, who continues to work in advocacy for all people living
with narcolepsy of all ages, I applaud the FDA for approving WAKIX
in pediatric patients 6 years of age and older," said Monica Gow, Co-Founder and Executive Director of
Wake Up Narcolepsy. "This new approval offers a promising
non-scheduled treatment option for children with narcolepsy,
marking an important step forward in addressing the unmet medical
needs of these children."
About Narcolepsy
Narcolepsy is a rare, chronic,
debilitating neurological disease of sleep-wake state instability
that impacts approximately 170,000 Americans and is primarily
characterized by its cardinal symptom excessive daytime sleepiness
(EDS), with or without cataplexy – along with other manifestations
of REM sleep dysregulation (hallucinations and sleep paralysis),
which intrude into wakefulness. EDS is the inability to stay awake
and alert during the day and is the symptom that is present in all
people living with narcolepsy. In most patients, narcolepsy is
caused by the loss of hypocretin/orexin, a neuropeptide in the
brain that supports sleep-wake state stability. This disease
affects men and women equally, with typical symptom onset in
adolescence or young adulthood; however, it can take up to a decade
to be properly diagnosed.
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 (EDS) or cataplexy in adult
patients with narcolepsy and for the treatment of EDS in pediatric
patients 6 years of age and older with narcolepsy. 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 (EDS) or cataplexy in
adult patients with narcolepsy and for the treatment of excessive
daytime sleepiness (EDS) in pediatric patients 6 years of age and
older 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. WAKIX is
contraindicated in patients with severe hepatic impairment and not
recommended in patients with end-stage renal disease (ESRD).
Adverse Reactions
In the placebo-controlled clinical
trials conducted in adult 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.
In the placebo-controlled phase of the clinical trial conducted
in pediatric patients 6 years and older with narcolepsy with or
without cataplexy, the most common adverse reactions (≥5% and
greater than placebo) for WAKIX were headache (19%) and insomnia
(7%). The overall adverse reaction profile of WAKIX in the
pediatric clinical trial was similar to that seen in the adult
clinical trial program.
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.
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. WAKIX may reduce
the effectiveness of sensitive CYP3A4 substrates, including
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.
Use in Specific Populations
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
for treatment of excessive daytime sleepiness in pediatric patients
less than 6 years of age with narcolepsy.
The safety and effectiveness of WAKIX have not been established
for treatment of cataplexy in pediatric patients with
narcolepsy.
WAKIX is extensively metabolized by the liver. WAKIX is
contraindicated in patients with severe hepatic impairment. Dosage
adjustment is recommended 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
eGFR <60 mL/minute/1.73
m2.
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 plans to explore the therapeutic potential of
pitolisant in additional indications; our ongoing and planned
clinical trials; our ability to expand the scope of our license
agreements with Bioprojet Société Civile de Recherche
("Bioprojet"); 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 other product candidates; our estimates regarding expenses,
future revenue, capital requirements and additional financing
needs; our ability to identify, acquire and integrate 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 22, 2024, 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 Investor Contact:
Brennan Doyle
484-539-9700
bdoyle@harmonybiosciences.com
Harmony Biosciences Media Contact:
Cate McCanless
202-641-6086
cmccanless@harmonybiosciences.com
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