PLYMOUTH MEETING, Pa.,
June 6, 2023 /PRNewswire/ -- Harmony
Biosciences Holdings, Inc. ("Harmony") (Nasdaq: HRMY), a
pharmaceutical company dedicated to developing and commercializing
innovative therapies for patients with rare neurological diseases,
today announced the presentation of safety and efficacy data from a
Phase 2 proof-of-concept study evaluating pitolisant for the
treatment of excessive daytime sleepiness (EDS) in people with
Prader-Willi syndrome (PWS) at the 37th Annual Meeting of the
Associated Professional Sleep Societies (APSS), known as "SLEEP
2023." The positive signal supports further development to
determine if pitolisant has the potential to address an unmet
medical need for people with PWS experiencing EDS.
Notably, both the high- and low-dose pitolisant treatment arms
demonstrated greater mean improvement from baseline in the Epworth
Sleepiness Scale for Children and Adolescents (ESS-CHAD, Parent / Caregiver version) scores in
the overall patient population when compared to placebo. A
dose-response was observed with a relatively higher response rate
occurring in the high dose pitolisant group compared to the low
dose pitolisant group. This proof-of-concept study was not powered
to demonstrate statistical significance and was designed for signal
detection.
Harmony is working with the U.S. FDA to discuss the results from
this study and to finalize the Phase 3 registrational study, which
it expects to initiate in 2H 2023.
"The positive signal from our Phase 2 study represents a
milestone in our quest to address the unmet medical need
surrounding excessive daytime sleepiness in Prader-Willi syndrome,
for which there is currently no approved treatment," said
Kumar Budur, M.D., M.S., Chief
Medical Officer at Harmony Biosciences. "Given the lack of existing
treatment options for people with Prader-Willi syndrome, these
findings represent a step forward in our efforts to improve the
quality of life of individuals living with this condition and our
commitment to rigorously pursuing promising new indications for
pitolisant beyond narcolepsy."
Among the 15,000 to 20,000 Americans living with PWS, more than
half of them experience symptoms of EDS. There is currently no
FDA-approved treatment for EDS management in people with PWS.
"Prader-Willi syndrome impacts and imposes challenges on people
living with the disease and their entire family making the
importance of new clinical advancements difficult to overstate,"
said Susan Hedstrom, Executive
Director, Foundation for Prader-Willi Research, and Paige Rivard, Chief Executive Officer,
Prader-Willi Syndrome Association | USA. "As advocates, we witness the remarkable
courage, determination, and love within the PWS community. By
moving forward clinical research and hastening innovation to
address current gaps in treatment, we are hopeful to one day reduce
the symptom burden for those living with PWS and their families so
they can continue living even more fulfilling lives."
Harmony will also present the Phase 2 data during the
Prader-Willi Syndrome Association | USA (PWSA | USA) National Convention in Orlando, Florida from June 21-24 as well as at the Foundation for
Prader-Willi Research 2023 Research Symposium and Family Conference
happening in Denver, Colorado from
October 5-7.
Poster 510: Primary Efficacy and Safety Results of a Phase 2
Double-Blind, Placebo-Controlled Proof of Concept, Signal Detection
Study of Pitolisant in Prader-Willi Syndrome
The Phase 2 clinical trial was a randomized, double-blind,
placebo-controlled study designed to assess the safety and efficacy
of pitolisant in people living with PWS. In the trial, eligible
patients who were genetically confirmed to have PWS with EDS were
enrolled in an 11-week double-blind treatment phase that included a
3-week titration phase and eight weeks of stable dosing.
Participants were then randomized (1:1:1) to receive low- or
high-dose pitolisant, or a matching placebo based on age (n=65).
The primary efficacy endpoint was change from baseline to week 11
in total score for the parent or caregiver version of
ESS-CHAD. Summary statistics for
the primary efficacy endpoint of change from baseline in total
ESS-CHAD score were applied.
Results from the study include:
- Pitolisant demonstrated a clinically meaningful change (defined
as a ≥ 2-point improvement on this scale) of 3.7 to 5.5 points
across all age groups in both the high- and low-dose treatment arms
with the strongest signal observed in the youngest age group
(children ages 6-11);
- In two of the three age groups (children and adults), there was
a clinically meaningful difference (minimum of 2 points) between
pitolisant and placebo, driven by the high dose pitolisant
treatment group;
- Most common adverse events included anxiety (11.9% pitolisant;
4.3% placebo), irritability (9.5% pitolisant; 4.3% placebo) and
headache (7.1% pitolisant; 4.3% placebo); and
- No Serious Adverse Events (SAE) were reported in the pitolisant
group, and one SAE (deep vein thrombosis) was reported in the
placebo group.
Pitolisant is marketed as WAKIX® in the U.S. and is
FDA approved to treat EDS or cataplexy in adult patients with
narcolepsy. Pitolisant is not approved for use in patients with PWS
and is currently being evaluated as an investigational agent in
this patient population.
About Prader-Willi Syndrome
PWS is an orphan/rare,
genetic neurological disorder with many of the symptoms resulting
from hypothalamic dysfunction. The hypothalamus is the part of the
brain that controls both sleep-wake state stability and signals
that mediate the balance between hunger and satiety, resulting in
two of the main symptoms in patients with PWS, EDS and hyperphagia
(an intense persistent sensation of hunger accompanied by food
preoccupations, an extreme drive to consume food, food-related
behavior problems, and a lack of normal satiety). Other features
include low muscle tone, short stature, behavioral problems, and
cognitive impairment. Approximately 15,000 to 20,000 people in the
U.S. live with PWS, and over half of them experience EDS.
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 impact of the COVID-19 pandemic, including any
current and future variants; 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 under our 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;
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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