PLYMOUTH
MEETING, Pa., Dec. 7, 2023
/PRNewswire/ -- Harmony Biosciences Holdings, Inc. ("Harmony" or
the "Company") (Nasdaq: HRMY) today announced positive topline
results from its Phase 2 signal detection study evaluating the
safety and efficacy of pitolisant in adult patients with myotonic
dystrophy type 1 (DM1).
A clinically meaningful improvement was demonstrated on the
primary efficacy endpoint, the change from baseline to the end of
the double-blind period for excessive daytime sleepiness (EDS) as
measured by the Daytime Sleepiness Scale (DSS). A clinically
meaningful improvement was also demonstrated for fatigue, a
secondary efficacy endpoint measured by the Fatigue Severity Scale
(FSS). EDS and fatigue occur in up to 80-90% of patients with DM1
and impact daily functioning as much as muscular symptoms (myotonia
and muscle weakness).
"These strong topline results add to the body of evidence
supporting the effectiveness of pitolisant for improving EDS," said
Jeffrey M. Dayno, M.D., President and CEO of Harmony Biosciences. "In
addition, a positive signal for pitolisant has been demonstrated
for fatigue, suggesting it could be a potential new treatment
option for this symptom as well. We are encouraged by these
results, which underscore our commitment to translating innovative
science into therapeutic possibilities for patients living with
unmet medical needs."
Topline results include:
- Clinically meaningful improvements were demonstrated in EDS as
measured by DSS, Epworth Sleepiness Scale (ESS), and Clinical
Global Impression of Severity (CGI-S) of EDS.
On DSS, the mean change from baseline to end of
double-blind period was
-2.5 and -1.0 for the higher dose and lower dose pitolisant
treatment groups, respectively, compared to -0.2 for placebo.
On ESS, the mean change from baseline to end of
double-blind period was
-4.88 for the higher dose pitolisant treatment group compared to
-0.10 for placebo.
On CGI-S, the mean change from baseline to end
of double-blind period was
-0.9 for the higher dose pitolisant treatment group compared to
-0.1 for placebo.
- Clinically meaningful improvements were demonstrated for
fatigue as measured by the Fatigue Severity Scale (FSS).
On FSS, the mean change from baseline to end of
double-blind period was
-0.86 and -0.36 for the higher dose and lower dose pitolisant
treatment groups, respectively, compared to -0.13 for placebo.
- A clear and consistent dose-response was demonstrated with the
higher dose pitolisant group showing a greater response than the
lower dose group across the study endpoints.
- Safety and tolerability profile in adult patients with DM1 was
consistent with the established safety profile of pitolisant with
no new safety signals detected and no serious adverse events
reported.
"EDS is the most common non-muscular complaint in patients
living with DM1, being present in the majority of patients," said
Dr. Jean-Denis Brisson, Centre Intégré Universitaire De Santé
Et De Services Sociaux du Saguenay-Lac-Saint-Jean. "The positive
signals from this Phase 2 study are very encouraging, and
support pitolisant as a potential treatment option for DM1."
This Phase 2 signal detection study was a randomized,
double-blind, placebo-controlled study in adults ages 18-65 with
DM1. This study was not powered to demonstrate statistical
significance. Thirty patients were randomized at baseline to
receive lower dose pitolisant, higher dose pitolisant, or placebo
in a 1:1:1 treatment ratio titrated over three weeks, followed by
eight weeks of stable dosing.
"These positive signals for pitolisant are promising news for
the DM1 patient community, where 80-90 percent of the approximately
40,000 diagnosed DM1 patients in the U.S. experience significant
EDS and fatigue with no FDA-approved treatments available," said
Kumar Budur, M.D., M.S., Chief
Medical Officer at Harmony Biosciences. "The strong signals for
pitolisant reinforce our confidence in it as a potential treatment
option worthy of further study in patients with DM1."
The full dataset from this trial will include findings from
other secondary outcomes, including the Myotonic Dystrophy Health
Index (MDHI), cognitive functions, and the safety and effectiveness
of pitolisant from the ongoing Open-Label Extension (OLE) Phase.
Additional results from the trial will be shared early next year.
Detailed results will be presented at an upcoming medical meeting
and will be submitted for publication.
Pitolisant is marketed as WAKIX® in the U.S. and
is FDA approved to treat excessive daytime sleepiness or cataplexy
in adults with narcolepsy. Pitolisant is not approved for use in
patients with DM1 and is currently being evaluated as an
investigational agent in this patient population.
About Myotonic Dystrophy Type 1
Myotonic
dystrophy Type 1 (DM1) is the most common form of adult-onset
muscular dystrophy. It is a genetic disorder inherited in an
autosomal-dominant pattern. Latest estimates suggest a prevalence
of about one per 2,100 people with the genetic defect for DM1. This
equates to about 150,000 people in the U.S. with the genetic defect
for DM1. Estimates suggest there are 40,000 people currently
diagnosed with DM1 in the U.S., with up to 90% of them reporting
EDS and fatigue and over 60% of them experiencing cognitive
dysfunction.
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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