PLYMOUTH
MEETING, Pa., June 5, 2024
/PRNewswire/ -- Harmony Biosciences (Nasdaq: HRMY) presented data
from its Phase 2 signal detection study showing that pitolisant
reduced excessive daytime sleepiness (EDS) and fatigue in adults
with Myotonic dystrophy Type 1 (DM1).
"More than 80 percent of DM1 patients experience EDS and
fatigue, which patient-reported outcomes research has shown to be
nearly as debilitating as the primary symptoms of DM1, namely
myotonia and muscle weakness,"1 said
Kumar Budur, M.D., M.S., Chief
Medical and Scientific Officer of Harmony Biosciences. "The
findings from our signal detection study evaluating pitolisant,
which is believed to promote wakefulness through histamine, present
an exciting opportunity to develop new treatments for EDS and
fatigue in DM1, narcolepsy, and the other sleep/wake disorders we
are investigating through our lifecycle management programs that
will involve Next-Generation formulations of pitolisant."
Notably, there was greater mean improvement from baseline to
Week 11 in both EDS (as measured by the Daytime Sleepiness Scale)
and fatigue (as measured by the Fatigue Severity Scale) compared to
placebo. The overall disease burden also signaled greater
improvement for pitolisant compared to placebo, with the higher
dose pitolisant group showing a stronger efficacy signal. This
study was designed for signal detection and was not powered to
demonstrate statistical significance.
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.
"Given the potential opportunity of pitolisant for treating EDS
and fatigue in patients with DM1, we plan to progress our DM1
development program through a pivotal Phase 3 study using the
Next-Generation 2 (NG2) formulation of pitolisant, which is
designed to deliver an optimized pharmacokinetic profile and higher
dosage strength," Budur added. "The NG2 formulation could be
promising given the positive findings we observed across the EDS
and fatigue endpoints within the higher dose pitolisant treatment
arm. These efforts are integral to our broader life cycle
management programs, which, if successful, could benefit over
100,000 patients living with unmet medical needs."
Poster 378: Primary Efficacy and Safety Results of a Phase 2,
Double-Blind, Placebo-Controlled, Proof of Concept, Signal
Detection Study of Pitolisant in Myotonic Dystrophy
The Phase 2 signal detection study was a randomized,
double-blind, placebo-controlled study designed to evaluate the
efficacy and safety of pitolisant in the treatment of EDS and other
non-muscular symptoms in adults with DM1. Eligible patients were
confirmed to have DM1 and enrolled in an 11-week double-blind
treatment phase that included a 3-week titration period and an
8-week stable dose period. Participants were randomized to receive
higher or lower dose pitolisant, or a matching placebo.
The primary efficacy endpoint was the change from baseline to
Week 11 in Daytime Sleepiness Scale score. Additional efficacy
endpoints included the change from baseline to Week 11 in Epworth
Sleepiness Scale score, Fatigue Severity Scale score, Clinical
Global Impression of Severity (for EDS) score, and Myotonic
Dystrophy Health Index score.
Results from the study include:
- Mean improvement on the Daytime Sleepiness Scale (primary
endpoint) was greater for pitolisant. Compared with placebo, a
dose-response relationship was observed from baseline to Week
11:
-
- Higher Dose Pitolisant (n=8): -2.5
- Lower Dose Pitolisant (n=8): -1.0
- Placebo (n=9): -0.2
- Mean improvement on the other secondary efficacy endpoints
(EDS, fatigue, disease burden) was also greater for pitolisant
versus placebo, with higher dose pitolisant showing a stronger
efficacy signal from baseline to Week 11.
-
- Epworth Sleepiness Scale:
-
- Higher Dose Pitolisant (n=8): -4.9
- Lower Dose Pitolisant (n=9): 1.3
- Placebo (n=10): -0.1
- Fatigue Severity Scale:
-
- Higher Dose Pitolisant (n=8): -0.9
- Lower Dose Pitolisant (n=9): -0.4
- Placebo (n=10): -0.1
- Clinical Global Impression of Severity (for EDS):
-
- Higher Dose Pitolisant (n=8): -0.9
- Lower Dose Pitolisant (n=9): -0.2
- Placebo (n=10): -0.1
- Myotonic Dystrophy Health Index
-
- Higher Dose Pitolisant (n=8): -9.1
- Lower Dose Pitolisant (n=9): -2.9
- Placebo (n=10): 0.4
- The rate of adverse events was similar for pitolisant and
placebo. The safety and tolerability of pitolisant in patients with
DM1 were consistent with its known safety profile.
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 DM1 and is currently being evaluated as an
investigational agent in this patient population.
1 Heatwole C, Bode R, Johnson N, et al.
Patient-reported impact of symptoms in myotonic dystrophy type 1
(PRISM-1). Neurology. 2012; 79(4):348-57. Erratum in: Neurology.
2012; 79(13):1411.
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.
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 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 full
year 2024 net product revenue, expectations for the growth and
value of WAKIX, plans to submit an sNDA for pitolisant in
idiopathic hypersomnia; our future results of operations and
financial position, business strategy, products, prospective
products, product approvals, the plans and objectives of management
for future operations and future results of anticipated products.
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 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 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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