PLYMOUTH
MEETING, Pa., April 11,
2024 /PRNewswire/ -- Harmony Biosciences Holdings,
Inc. (Nasdaq: HRMY) today announced an exclusive licensing
agreement with Bioprojet to develop, manufacture and commercialize
TPM-1116, a highly potent and selective oral orexin-2 receptor
(OX2R) agonist that will be evaluated for the treatment of
narcolepsy and other sleep/wake disorders. TPM-1116 represents a
new chemical series of OX2R agonists with the potential for a
best-in-class clinical profile.
Narcolepsy and other hypersomnolence disorders continue to be a
large market opportunity with significant unmet medical
need. The agreement will accelerate the development of
this orexin-2 receptor agonist and is expected to further
Harmony's leadership in the sleep/wake space, reinforcing its
commitment to advancing innovative treatments for patients living
with unmet medical needs, according to Jeffrey M. Dayno, M.D., Harmony Biosciences
President and CEO.
"Orexin agonism is an exciting area of sleep disorder research
and represents the next novel mechanism of action for the treatment
of narcolepsy since the launch of WAKIX. We also see potential
synergies between TPM-1116 and our lead product, WAKIX, and
new formulations of pitolisant, because of the interplay between
histamine and orexin in the hypothalamus," Dayno said. "We believe
TPM-1116, a new chemical series of orexin 2 agonist, could emerge
with a potential best-in-class clinical profile based on its
potency and selectivity, along with its strong preclinical safety
profile and potential for once daily dosing. We look forward
to working with Bioprojet and advancing the development program for
TPM-1116 as part of our growth strategy."
"We are pleased that this new project to develop a potentially
best-in-class orexin-2 receptor agonist will extend the productive
collaboration between Bioprojet and Harmony in the field of sleep
medicine beyond the successful commercialization of WAKIX in
narcolepsy and the discovery of novel formulations of pitolisant to
extend the pitolisant franchise," said Professor Jean-Charles Schwartz, Co-Founder of Bioprojet
and member of the French and European Academies of
Science.
Under the agreement, Harmony will pay Bioprojet an upfront
license fee of $25.5 million for the
exclusive right to develop, manufacture and commercialize TPM-1116
in the U.S. and Latin American territories. In addition, Harmony is
obligated to pay up to $127.5 million
upon achievement of development and regulatory milestones and up to
$240 million upon achievement of
sales-based milestones. Finally, Harmony will pay a royalty rate in
the mid-teens on sales of product in the licensed territories.
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.
About Bioprojet
Bioprojet is a pharmaceutical
company headquartered in Paris, France. Its activity is focused on the design,
synthesis and development of novel classes of drugs for unmet
medical needs, such as Pitolisant (Wakix®). Bioprojet is
commercially active in 7 western European countries through its own
organization and commercially covering the rest of the world
through distributors and licensees.
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.
Forward-Looking Statements
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 and our license for TPM-1116. 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
regarding pitolisant and TPM-1116; our ongoing and planned clinical
trials; our commercialization, marketing and manufacturing
capabilities and strategy; and failure to successfully execute our
strategy, including any delays in our planned future growth. 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:
Luis Sanay, CFA
445-235-8386
lsanay@harmonybiosciences.com
Harmony Biosciences Media Contact:
Cate McCanless
202-641-6086
cmccanless@harmonybiosciences.com
View original content to download
multimedia:https://www.prnewswire.com/news-releases/harmony-biosciences-announces-exclusive-agreement-to-develop-and-commercialize-tpm-1116-a-highly-potent-and-selective-oral-orexin-2-receptor-agonist-302113794.html
SOURCE Harmony Biosciences
