PLYMOUTH
MEETING, Pa., Oct. 5, 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 the presentation
of new secondary endpoint data, including improvements in
behavioral disturbances, from its Phase 2 signal-detection study
evaluating pitolisant for the treatment of excessive daytime
sleepiness (EDS) in Prader-Willi syndrome (PWS), at the 2023
Foundation for Prader-Willi Research (FPWR) Symposium and Family
Conference. The company also announced that it anticipates
initiating its Phase 3 registrational TEMPO study in Q4 2023.
The poster presentation of secondary outcomes data included
improvements in behavioral symptoms (as measured by the Aberrant
Behavioral Checklist-2), especially in the higher-dose pitolisant
group. Reductions in the caregiver rating of EDS severity were also
observed as were some improvements in hyperphagia, even though
baseline hyperphagia scores were in the normal to mild range. The
overall rate of adverse events was similar for pitolisant and
placebo, and the safety/tolerability profile was consistent with
the known profile for pitolisant.
"We recognize the urgency for innovative treatments that help
alleviate the profound unmet medical needs of individuals with PWS
and their dedicated caregivers," said Kumar
Budur, MD, Chief Medical Officer at Harmony Biosciences.
"This is particularly crucial given the absence of an FDA-approved
treatment for EDS in PWS, coupled with the prevalent and severe
behavioral symptoms associated with this condition. We are
encouraged by these findings from our Phase 2 signal-detection
study, which build upon the favorable primary study outcome and
provide additional hope to this community as we pursue a potential
new indication for pitolisant."
The results from the Phase 2 signal-detection study informed the
protocol design for the upcoming Phase 3 registrational TEMPO
study, a randomized, double-blind, placebo-controlled, multicenter,
global clinical study that will further assess the safety and
efficacy of pitolisant in patients with PWS, ages ≥ 6 years. This
study is expected to be initiated in Q4 2023. There are currently
15,000 – 20,000 people in the US living with PWS. More than half of
them experience EDS and the majority of them have behavioral
disturbances.
Poster: Secondary Outcomes from a Phase 2, Double-Blind,
Placebo-Controlled Signal-Detection, Proof-of-Concept Study of
Pitolisant in Prader-Willi Syndrome
The Phase 2 clinical trial was a randomized, double-blind,
placebo-controlled signal-detection, proof-of-concept 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 and who had 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
(n=65) were randomized (1:1:1) to receive lower- or higher-dose
pitolisant, or a matching placebo based on age.
Secondary/exploratory endpoints included change from baseline in
Caregiver Global Impression of Severity (CaGI-S) for EDS;
behavioral disturbance, as measured using the Aberrant Behavior
Checklist-2 (ABC-2); and Hyperphagia, assessed using the
Hyperphagia Questionnaire for Clinical Trials (HQ-CT) in
conjunction with the Food Safe Zone Questionnaire.
This proof-of-concept study was not powered to demonstrate
statistical significance and was designed for signal detection.
Key results include:
- Reductions in behavioral disturbances among the youngest age
group (6 to <12 years) were observed across all ABC-2 domains
especially in the higher-dose pitolisant group.
Irritability: higher-dose, -5.5; lower-dose,
-3.0; placebo, -1.5
Social withdrawal: higher-dose, -4.9; lower-dose, -1.6; placebo,
-3.1
Hyperactivity/noncompliance: higher-dose, -4.6; lower-dose, -0.9;
placebo, -3.0
Inappropriate speech: higher-dose, -2.0; lower-dose, -0.4; placebo,
-0.6
Stereotypic behavior: higher-dose, -1.0; lower-dose, -0.2; placebo,
-0.6
- Reductions in CaGI-S scores were greater for pitolisant
compared with placebo in the children (higher-dose, -1.1;
lower-dose, -1.0; placebo, -0.5) and adult (higher-dose, -1.0;
lower-dose, -2.0; placebo, -0.7) age groups.
A reduction of -1.0 or more was seen in the mean
change from baseline to week 11 in the children and adult
subgroups, meeting the clinical significance threshold per The
American Academy of Sleep Medicine (AASM).
- Some improvements in hyperphagia were noted in children
(higher-dose, -2.0; lower-dose, -2.5; placebo, 0.1) and adults
(higher-dose, -3.4; lower-dose, -3.0; placebo, -1.7) even though
baseline hyperphagia scores were in the normal/mild range.
Despite the trial not enriching for hyperphagia
and HQ-CT scores being relatively low at baseline, encouraging
trends toward improvements were seen compared with placebo,
especially in the children age group.
- There was an unusually large placebo response in the adolescent
age group, due to data from a single outlier, resulting in an
outsized impact on the magnitude of the placebo response not only
in the adolescent age group but also in the overall study
population.
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 and the
majority of them have behavioral disturbances.
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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