FDA confirms the favorable benefit-risk
profile of WAKIX
Harmony Biosciences focused on continuing to
advance its pipeline assets across three rare CNS franchises;
anticipates at least one new product or indication launch annually
over the next five years
PLYMOUTH
MEETING, Pa., June 25,
2024 /PRNewswire/ -- Harmony Biosciences Holdings,
Inc. (Nasdaq: HRMY), today announced that the U.S. Food and Drug
Administration denied the Citizen Petition filed by a short seller
claiming that WAKIX is not safe and effective for the
treatment of excessive daytime sleepiness (EDS) and cataplexy in
adults with narcolepsy. The Agency's decision to reject the
Petition was anticipated and confirms the Company's long-held
position that the allegations in the Petition were unfounded and
without merit.
In its denial, the FDA rejected all three requests from the
Petitioner including withdrawal for all indications, immediate
alert distribution ('Dear HCP Letter') to prescribers, and
transitioning to a Compassionate Use Program with a REMS protocol,
and stated "the FDA determined that WAKIX has a favorable
benefit-risk profile under its approved conditions of use, and your
Petition did not provide information that changes that
assessment."1
The FDA denied the Petition after approving the supplemental New
Drug Application (sNDA) for WAKIX on June
21, 2024, which expanded the indication for WAKIX to include
the treatment of EDS in pediatric patients 6 years of age and older
with narcolepsy. The denial letter states, "the FDA has carefully
considered the information submitted in the Petition, other data
available to the Agency, and relevant published literature. Based
on our review of these materials and for the reasons stated, the
Petition is denied."2
Harmony Biosciences stated:
"We are pleased with the FDA's decision
to deny the short seller Petition filed in March 2023, which tried to cast doubt on a safe
and effective treatment while deliberately attempting to impact our
stock price for profit. We appreciate the Agency's careful review
of the unfounded claims in the Petition and its definitive action
to deny the claims and resolve any potential doubt about the
favorable benefit-risk profile of WAKIX.
Looking ahead, we confirm our outlook that WAKIX
represents a billion-dollar plus market opportunity in adult
narcolepsy alone, and we are well on our way to achieving further
growth in the pitolisant franchise. We are also on track toward
filing an sNDA for WAKIX in idiopathic hypersomnia later this year
(2H 2024). In anticipation of the confirmation of the favorable
benefit-risk profile of WAKIX, we have already been working on the
next-generation formulations of pitolisant to address unmet medical
needs. These formulations are designed to provide meaningful
improvement, such as an enhanced pharmacokinetic (PK) profile and
higher dosage range to drive greater efficacy. These innovations
are expected to generate new IP to extend the pitolisant
franchise out beyond 2040.
Beyond WAKIX, we have expanded our pipeline and
diversified our portfolio resulting in three promising orphan rare
CNS franchises in advanced stages of development, each with the
potential to generate $1 billion to
$2 billion in peak sales. These
franchises are protected by patents extending into the late 2030s
to mid-2040s. As we continue to execute our growth strategy, we are
now poised to lead as a patient-centered CNS biotechnology company,
providing innovative treatments for patients with unmet medical
needs while driving substantial and durable value creation. Our
pipeline consists of eight assets being studied across 13
development programs within these three CNS franchises. Three of
our development programs are in Phase 3 trials and we have two
Phase 3 ready assets that we are working on. With this late-stage
pipeline, we anticipate launching at least one new product or
indication annually over the next five years and have the potential
to bring new treatment options to hundreds of thousands of people
living with rare diseases."
The FDA's detailed response letter can be found at the following
link:
https://downloads.regulations.gov/FDA-2023-P-1273-0005/attachment_1.pdf.
1 FDA Response Letter, Docket No: FDA-2023-P-1273,
Page 12, Paragraph 3, Sentence 3.
2 FDA Response Letter, Docket No: FDA-2023-P-1273, Page
1, Paragraph 3, Sentence 1-2.
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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