(BUSINESS WIRE)--Takeda (TSE:4502/NYSE:TAK) announced that the U.S. Food and Drug Administration (FDA) approved
ORZEYFUL™ (oveporexton), an oral orexin receptor 2 (OX2R) agonist, for
the treatment of narcolepsy type 1 (NT1, narcolepsy with cataplexy) in
adults.* The persistent 24-hour nature of NT1 is driven by orexin
deficiency and can severely impact people’s lives. As a first-in-class
orexin treatment, ORZEYFUL is the only medicine indicated in the U.S. to
treat the disease holistically rather than individual symptoms.
“The FDA approval of ORZEYFUL marks a new chapter for the narcolepsy
type 1 community, as we introduce an entirely new class of medicine that
will potentially redefine how this disease is managed and how people
feel on treatment,” said Julie Kim, president and chief executive
officer of Takeda. “We are proud to have discovered and developed this
orexin treatment innovation and will bring it to adults living with NT1
as quickly as possible.”
NT1 is a rare, chronic neurological disease driven by a loss of
orexin and affects an estimated 120,000 people in the U.S. People with
NT1 experience excessive daytime sleepiness, cataplexy (sudden loss of
muscle tone), cognitive symptoms and disrupted nighttime sleep that can
severely impact multiple aspects of daily life, including work,
education and social interactions.
"For those of us living with narcolepsy type 1, symptoms reshape
everyday life and extend far beyond what most people understand about
the condition," said Julie Flygare, President and CEO at Project Sleep
and a person with NT1. "ORZEYFUL’s approval is a historic moment that
expands our treatment choices and gives me great hope for the future and
for our community."
“Until now, people have managed narcolepsy type 1 with treatments
that target symptom relief,” said Dr. Emmanuel Mignot, M.D., Ph.D.,
principal U.S. investigator in the ORZEYFUL Phase 3 program. “As the
first and only approved orexin therapy to treat the broad spectrum of
the disease, ORZEYFUL can enable a different kind of conversation in the
doctor’s office about treatment options.”
The approval is based on a comprehensive clinical program including
the global Phase 3 FirstLight (TAK-861-3001) and RadiantLight
(TAK-861-3002) studies that showed oveporexton offers statistically
significant improvements across the full range of symptoms of the
disease. These included improvements in excessive daytime sleepiness,
cataplexy and health-related quality of life. Oveporexton was generally
well-tolerated with a safety profile consistent across clinical studies
to date. The most common side effects include trouble sleeping
(insomnia), urinary urgency, urinary frequency and excessive saliva.
Learn more about the Phase 3 data results here.
"With this approval, we are turning scientific discovery into reality
for adults living with narcolepsy type 1," said Andy Plump, M.D.,
Ph.D., President, Research & Development, Takeda. "ORZEYFUL is just
the beginning. With orexin emerging as a powerful therapeutic pathway,
Takeda is unlocking the potential of this new class of medicine for
patients across a range of disorders.”
Next Steps for ORZEYFUL Availability
The controlled substance classification for ORZEYFUL is currently
under review by the Drug Enforcement Administration (DEA) and is
expected within 90 days. After the controlled substance classification
is determined, ORZEYFUL will be made available through a specialty
pharmacy to U.S. healthcare providers and adults living with NT1. To
sign up for updates visit ORZEYFUL.com.
The FDA approval is not expected to have a significant impact on the
full year consolidated financial forecast for the fiscal year ending
March 31, 2027.
*For information regarding the submission of the new drug application
for oveporexton to the U.S. FDA, please refer to Takeda’s press release
dated February 10, 2026, “U.S.
Food and Drug Administration Accepts New Drug Application and Grants
Priority Review for Takeda’s Oveporexton (TAK-861) as a Potential
First-in-Class Therapy for Narcolepsy Type 1”.
About ORZEYFUL (oveporexton)
ORZEYFUL (oveporexton) is an oral orexin receptor 2 (OX2R) agonist,
which selectively stimulates the OX2R to restore signaling and address
the underlying orexin deficiency associated with narcolepsy type 1
(NT1). By activating OX2Rs, ORZEYFUL promotes wakefulness and reduces
abnormal rapid eye movement (REM)-sleep like phenomena, including
cataplexy (sudden and temporary loss of muscle tone), to address a range
of daytime and nighttime symptoms as evaluated in clinical studies and
consistent with the approved label.
INDICATION
ORZEYFUL is indicated for the treatment of narcolepsy type 1 (narcolepsy with cataplexy) in adult patients.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
ORZEYFUL is contraindicated in patients taking strong CYP3A inhibitors.
WARNINGS AND PRECAUTIONS
Insomnia: In pooled phase 3 studies in patients with NT1, 60%,
55%, and 1% of patients in the ORZEYFUL 2 mg twice daily, ORZEYFUL 1 mg
twice daily, and placebo groups, respectively, developed insomnia.
Prior to ORZEYFUL treatment initiation, inform patients about the risk
of insomnia at initiation of treatment. If insomnia persists beyond 7
days and significantly impacts daytime functioning or quality of life,
consider ORZEYFUL dosage reduction or discontinuation.
Urinary Frequency and Urgency: ORZEYFUL may cause or worsen urinary frequency and urgency. In pooled phase 3 studies in patients with NT1:
- 58%, 53%, and 5% of patients in the ORZEYFUL 2 mg twice daily,
ORZEYFUL 1 mg twice daily, and placebo groups, respectively, developed
urinary frequency.
- 16%, 15%, and 1% of patients in the ORZEYFUL 2 mg twice daily,
ORZEYFUL 1 mg twice daily, and placebo groups, respectively, developed
urinary urgency.
These lower urinary tract symptoms are consistent with ORZEYFUL’s
mechanism of action through agonism of the orexin receptor 2 (OX2R) on
central micturition pathways. Prior to initiation of ORZEYFUL treatment,
inform patients about the risk of urinary frequency and urgency and
screen for lower urinary tract symptoms. Monitor ORZEYFUL-treated
patients with a history of overactive bladder for worsening urinary
tract symptoms.
Creatine Phosphokinase Elevations: In pooled phase 3 studies
in patients with NT1, asymptomatic creatine phosphokinase elevations
>5x ULN were observed in 11% (21/196) of ORZEYFUL-treated patients
and 5% (4/76) of placebo treated patients. Two of these cases were
characterized by markedly elevated CPK and transaminase levels; both
patients discontinued treatment. None of the cases were associated with
myoglobinuria or renal impairment. Advise patients to report unexplained
muscle pain, weakness, or dark urine, particularly when engaging in
vigorous physical activity or taking concomitant drugs associated with
myotoxicity.
ADVERSE REACTIONS
The most common adverse reactions (incidence ≥5% and greater than
placebo) reported in phase 3 studies with ORZEYFUL were insomnia,
pollakiuria, micturition urgency, and salivary hypersecretion.
DRUG INTERACTIONS
- Concomitant use with strong or moderate CYP3A inhibitors increases
oveporexton exposures, which may increase the risk of
ORZEYFUL-associated adverse reactions
- Concomitant use of strong and moderate CYP3A inducers can increase
oveporexton metabolism and decrease plasma levels of oveporexton, which
may decrease the effectiveness of ORZEYFUL
USE IN SPECIFIC POPULATIONS
Pregnancy: There is a pregnancy exposure registry that
monitors pregnancy outcomes in women who are exposed to ORZEYFUL during
pregnancy. Patients should be encouraged to enroll in the ORZEYFUL
pregnancy registry if they become pregnant. To enroll or obtain
information from the registry, patients can call 1-877-371-0309.
Available data from clinical trials with ORZEYFUL use during pregnancy
are insufficient to identify a drug-associated risk of major birth
defects, miscarriage, or other adverse maternal or fetal outcomes.
Lactation: There are no data available on the presence of
oveporexton in human milk, the effects on the breastfed infant, or the
effects on milk production. Animal studies indicate that oveporexton was
present in the milk of lactating rats. When a drug is present in animal
milk, it is likely that the drug will be present in human milk.
Hepatic Impairment: Avoid use of ORZEYFUL in patients with severe hepatic impairment (Child-Pugh C), as it has not been studied in this population.
Renal Impairment: Avoid use of ORZEYFUL in patients with severe renal
impairment on dialysis (eGFR <15 mL/minute), as it has not been
studied in this population.
DRUG ABUSE AND DEPENDENCE
ORZEYFUL contains oveporexton. Controlled substance schedule to be
determined after review by the Drug Enforcement Administration.
ORZEYFUL has potential for abuse and misuse. Carefully evaluate
patients for a recent history of drug abuse, especially those with a
history of CNS stimulant, and follow such patients closely, observing
them for signs of misuse or abuse of ORZEYFUL.
Important Note: Prescribing Information is subject to change pending DEA scheduling and final label publication.
Please click for Full Prescribing Information.
About Takeda’s Orexin Franchise
Takeda is the leader in orexin science with a tailored portfolio of
investigational orexin agonists in pre-clinical and clinical stages for
multiple-sleep wake disorders and other indications where orexin plays a
role including respiration, mood and metabolism. ORZEYFUL (oveporexton)
is the lead orexin receptor 2 (OX2R) agonist asset in Takeda’s orexin
franchise and has been approved by regulatory bodies in China and the
United States for the treatment of narcolepsy type 1 (NT1). The company
is also investigating other oral orexin agonists, including TAK-360
being investigated for the treatment of NT1, narcolepsy type 2 (NT2) and
idiopathic hypersomnia (IH), as well as TAK-495.
About Takeda
Takeda is focused on creating better health for people and a brighter
future for the world. We aim to discover and deliver life-transforming
treatments in our core therapeutic and business areas, including
gastrointestinal and inflammation, rare diseases, plasma-derived
therapies, oncology, neuroscience and vaccines. Together with our
partners, we aim to improve the patient experience and advance a new
frontier of treatment options through our dynamic and diverse pipeline.
As a leading values-based, R&D-driven biopharmaceutical company
headquartered in Japan, we are guided by our commitment to patients, our
people and the planet. Our employees in approximately 80 countries and
regions are driven by our purpose and are grounded in the values that
have defined us for more than two centuries. For more information, visit
www.takeda.com.
Important Notice
For the purposes of this notice, “press release” means this document,
any oral presentation, any question-and-answer session and any written
or oral material discussed or distributed by Takeda Pharmaceutical
Company Limited (“Takeda”) regarding this release. This press release
(including any oral briefing and any question-and-answer in connection
with it) is not intended to, and does not constitute, represent or form
part of any offer, invitation or solicitation of any offer to purchase,
otherwise acquire, subscribe for, exchange, sell or otherwise dispose
of, any securities or the solicitation of any vote or approval in any
jurisdiction. No shares or other securities are being offered to the
public by means of this press release. No offering of securities shall
be made in the United States except pursuant to registration under the
U.S. Securities Act of 1933, as amended, or an exemption therefrom. This
press release is being given (together with any further information
which may be provided to the recipient) on the condition that it is for
use by the recipient for information purposes only (and not for the
evaluation of any investment, acquisition, disposal or any other
transaction). Any failure to comply with these restrictions may
constitute a violation of applicable securities laws.
The companies in which Takeda directly and indirectly owns
investments are separate entities. In this press release, “Takeda” is
sometimes used for convenience where references are made to Takeda and
its subsidiaries in general. Likewise, the words “we”, “us” and “our”
are also used to refer to subsidiaries in general or to those who work
for them. These expressions are also used where no useful purpose is
served by identifying the particular company or companies.
Forward-Looking Statements
This press release and any materials distributed in connection with this
press release may contain forward-looking statements, beliefs or
opinions regarding Takeda’s future business, future position and results
of operations, including estimates, forecasts, targets and plans for
Takeda. Without limitation, forward-looking statements often include
words such as “targets”, “plans”, “believes”, “hopes”, “continues”,
“expects”, “aims”, “intends”, “ensures”, “will”, “may”, “should”,
“would”, “could”, “anticipates”, “estimates”, “projects”, “forecasts”,
“outlook” or similar expressions or the negative thereof. These
forward-looking statements are based on assumptions about many important
factors, including the following, which could cause actual results to
differ materially from those expressed or implied by the forward-looking
statements: the economic circumstances surrounding Takeda’s global
business, including general economic conditions in Japan and the United
States and with respect to international trade relations; competitive
pressures and developments; changes to applicable laws and regulations,
including tax, tariff and other trade-related rules; challenges inherent
in new product development, including uncertainty of clinical success
and decisions of regulatory authorities and the timing thereof;
uncertainty of commercial success for new and existing products;
manufacturing difficulties or delays; fluctuations in interest and
currency exchange rates; claims or concerns regarding the safety or
efficacy of marketed products or product candidates; the impact of
health crises, like the novel coronavirus pandemic; the success of our
environmental sustainability efforts, in enabling us to reduce our
greenhouse gas emissions or meet our other environmental goals; the
extent to which our efforts to increase efficiency, productivity or
cost-savings, such as the integration of digital technologies, including
artificial intelligence, in our business or other initiatives to
restructure our operations will lead to the expected benefits; and other
factors identified in Takeda’s most recent Annual Report on Form 20-F
and Takeda’s other reports filed with the U.S. Securities and Exchange
Commission, available on Takeda’s website at: https://www.takeda.com/investors/sec-filings-and-security-reports/ or at www.sec.gov.
Takeda does not undertake to update any of the forward-looking
statements contained in this press release or any other forward-looking
statements it may make, except as required by law or stock exchange
rule. Past performance is not an indicator of future results and the
results or statements of Takeda in this press release may not be
indicative of, and are not an estimate, forecast, guarantee or
projection of Takeda’s future results.
Medical Information
This press release contains information about products that may not
be available in all countries, or may be available under different
trademarks, for different indications, in different dosages, or in
different strengths. Nothing contained herein should be considered a
solicitation, promotion or advertisement for any prescription drugs
including the ones under development.
View source version on businesswire.com: https://www.businesswire.com/news/home/20260805760759/en/
