- LIVTENCITY Is the First and Only Post-Transplant Anti-CMV
Treatment Approved in Japan That Targets/Inhibits UL97 Protein
Kinase1
- CMV Is One of the Most Common and Serious Post-transplant
Infections and Can Lead to Secondary Infections and Serious
Consequences, Including Loss of Transplanted Organ and Failure of
Graft2,3
Takeda (TSE:4502/NYSE:TAK) today announced that LIVTENCITY®
(maribavir) has been approved by the Japanese Ministry of Health,
Labour and Welfare (MHLW) for post-transplant cytomegalovirus (CMV)
infection/disease that is refractory to existing anti-CMV
therapies.4 LIVTENCITY is the first and only post-transplant
anti-CMV treatment approved in Japan that targets and inhibits
pUL97 kinase and its natural substrates.1
“We are pleased by the approval of LIVTENCITY in Japan, which
will provide the transplant community with a new option for
treatment of post-transplant CMV infection in patients refractory
to other therapies,” said Yasushi Kajii, Head, R&D Japan Region
at Takeda. “A diagnosis of CMV infection can be particularly
challenging for patients, and serious complications such as
increased organ rejection and hospitalization rates can occur, when
not successfully treated. We believe LIVTENCITY has the potential
to help address the challenges faced by people with post-transplant
CMV and transform the treatment landscape for patients in
Japan.”
The approval is primarily based on the results of the Phase 3
SOLSTICE trial (NCT02931539), which evaluated the safety and
efficacy of LIVTENCITY versus alternative antiviral treatments for
patients with CMV infection/disease refractory* to prior therapies
who underwent hematopoietic stem cell transplant (HSCT) or solid
organ transplant (SOT), and the Japanese Phase 3 open-label study
in patients with CMV infection, including those with refractory*
CMV infection who underwent HSCT or SOT (NCT05137717).
In the SOLSTICE trial (maribavir n=235, alternative treatments
n=117), maribavir showed statistically significant improvement when
compared to alternative antiviral treatments at the end of Week 8
for the primary endpoint of confirmed CMV viremia clearancea in
post-transplant (HSCT or SOT) adults with refractory* CMV
infection.5 Of the 234 patients included in the safety evaluation,
adverse reactions (related cases) were observed in 141 patients
(60.3%).5
An open-label, multicenter, single-arm study was conducted to
evaluate the efficacy and safety in Japanese patients in
post-transplant (HSCT or SOT) adultsc (41 randomized, including 3
subjects with CMV infection refractory* to the most recently
administered anti-CMV agent). The primary endpoint of CMV viremia
clearanceb at the end of Study Week 8 was achieved in 33.3% of
patients with refractory* CMV infection.4 Of 41 subjects included
in the safety evaluation, adverse reactions (related events) were
observed in 36.6% (15 subjects). 4
About LIVTENCITY LIVTENCITY (maribavir), an orally
administered (tablet) anti-CMV compound, is the first and only
antiviral agent that targets and inhibits the CMV-specific UL97
protein kinase and thus its natural substrates.1 As of June 2024,
LIVTENCITY is approved in more than 30 countries for
post-transplant CMV refractory* to prior therapies, including such
major markets as Japan, the United States, Canada, Australia, the
European Union and China.
LIVTENCITY Product Overview in Japan
Product Name
LIVTENCITY 200 mg tablets.
Generic Name
Maribavir
Indications
The post-transplant cytomegalovirus (CMV)
infection/disease that is refractory to existing anti-CMV
therapies.
Precautions concerning
indications
- This drug should be administered to post-transplant patients
with CMV infection/disease who have responded inadequately to other
therapies.
- Efficacy and safety have not been studied in patients with CMV
infection of the central nervous system and CMV retinitis. Based on
nonclinical studies, this drug is expected to cross the blood-brain
barrier but has low potential to enter the central nervous
system.
Dosage and Administration
Usually, the recommended dosage for
adultsc is 400 mg of maribavir to be administered orally twice
daily.
About Takeda’s SOLSTICE Trial The TAK-620-303 (SOLSTICE)
trial (NCT02931539, EudraCT 2015-004725-13) was a Phase 3 global,
multicenter, randomized, open-label, active-controlled trial to
assess the efficacy and safety of maribavir treatment compared to
investigator-assigned treatment (alternative antiviral therapies)
in 352 HSCT and SOT recipients with CMV infections that were
refractory* or resistant to one or a combination of the alternative
antiviral therapies: ganciclovir, valganciclovir, foscarnet, or
cidofovir. Adult patients underwent a 2-week screening period,
followed by randomization 2:1 to maribavir (n=235) (400 mg, twice
daily) or alternative antiviral treatments (n=117) (as dosed by the
investigator) for up to 8 weeks. After completion of the treatment
period, subjects entered a 12-week follow-up phase.5 The trial’s
primary efficacy endpoint was confirmed CMV viremia clearance a at
the end of Week 8. The key secondary endpoint was confirmed CMV
viremia clearance and CMV infection symptom control† at the end of
Study Week 8 with maintenance of this treatment effect through
Study Week 16.5
About Cytomegalovirus (CMV) CMV is a beta herpesvirus
that commonly infects humans; serologic evidence of prior infection
can be found in 40-100% of various adult populations.6 CMV
typically resides latent and asymptomatic in the body but may
reactivate during periods of immunosuppression. Serious disease may
occur in individuals with compromised immune systems, which
includes patients who receive immunosuppressants associated with
various types of transplants including HSCT or SOT.5,7 Out of the
estimated 200,000 adult transplants per year globally, CMV is one
of the most common viral infections experienced by transplant
recipients, with an estimated incidence rate between 16-56% in SOT
recipients and 30-80% in HSCT recipients.7,8
In transplant recipients, reactivation of CMV infection can lead
to secondary infections and serious consequences, including graft
loss and, in extreme cases, can be fatal.2,3,5
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.
LIVTENCITY Safety Information Contraindications
Contraindications include Hypersensitivity to the active substance
or to any of the excipients and co‑administration with ganciclovir
or valganciclovir.
Special warnings and precautions for use Some maribavir
pUL97 resistance-associated substitutions confer cross-resistance
to ganciclovir and valganciclovir. CMV DNA levels should be
monitored, and resistance mutations should be investigated in
patients who do not respond to treatment. Treatment should be
discontinued if maribavir resistance mutations are detected.
LIVTENCITY is not expected to be effective in treating CMV CNS
infections (e.g. meningo‑encephalitis).
LIVTENCITY has the potential to increase the concentrations of
immunosuppressants that are cytochrome P450 (CYP)3A/P-gp substrates
with narrow therapeutic margins (including tacrolimus,
cyclosporine, sirolimus and everolimus). The plasma levels of these
immunosuppressants must be frequently monitored throughout
treatment with LIVTENCITY, especially following initiation and
after discontinuation of LIVTENCITY, and doses should be adjusted,
as needed.
The concomitant use of LIVTENCITY and certain medicinal products
may result in known or potentially significant medicinal product
interactions, some of which may lead to:
- possible clinically significant adverse reactions from greater
exposure of concomitant medicinal products.
- reduced therapeutic effect of LIVTENCITY.
Sodium content: This medicinal product contains less than 1 mmol
sodium (23 mg) per tablet, that is to say essentially
‘sodium‑free’.
Pregnancy & Breast-feeding: LIVTENCITY is not recommended
during pregnancy and in women of childbearing potential not using
contraception. Breast‑feeding should be discontinued during
treatment with LIVTENCITY.
Interactions Effect of other
medicinal products on maribavir: Co-administration of maribavir with
strong cytochrome P450 3A (CYP3A) inducers rifampicin, rifabutin or
St. John’s wort is not recommended. If co-administration of
maribavir with other strong or moderate CYP3A inducers (e.g.,
carbamazepine, efavirenz, phenobarbital and phenytoin) cannot be
avoided, the maribavir dose should be increased to 1 200 mg twice
daily. No dose adjustment is needed when maribavir is
co‑administered with CYP3A inhibitors.
Effect of maribavir on other medicinal
products: If dose adjustments
of concomitant medicinal products are made due to treatment with
maribavir, doses should be readjusted after treatment with
maribavir is completed.
Co-administration of maribavir with valganciclovir and
ganciclovir is contraindicated.
Concomitant administration of maribavir and medicinal products
that are sensitive substrates of CYP1A2 with a narrow therapeutic
window (e.g., tizanidine and theophylline) should be avoided due to
the risk for lack of efficacy of CYP1A2 substrates.
When the immunosuppressants tacrolimus, cyclosporine, everolimus
or sirolimus are co-administered with maribavir, immunosuppressant
levels should be frequently monitored throughout treatment with
maribavir, especially following initiation and after
discontinuation of maribavir and dose adjusted, when needed.
Caution should be exercised when maribavir and sensitive P-gp
substrates (e.g., digoxin, dabigatran) are co‑administered. Serum
digoxin concentrations should be monitored, and dose of digoxin may
need to be reduced, as needed (see Table 1).
Co‑administration of maribavir with sensitive BCRP substrates
such as rosuvastatin, is expected to increase their exposure and
lead to undesirable effects.
Adverse Reactions
Very common
(≥1/10)
Taste disturbance, Diarrhoea, Nausea,
Vomiting, Fatigue
Common
(≥1/100 to <1/10)
Headache, Abdominal pain upper, Decreased
appetite, Immunosuppressant drug level increased, Weight
decreased
The most commonly reported serious adverse reactions were
diarrhoea (2%) and nausea, weight decreased, fatigue,
immunosuppressant drug level increased, and vomiting (all occurring
at < 1%).
Please consult the LIVTENCITY (maribavir) approved label
before prescribing, particularly in relation to dosing and
treatment monitoring.
For Japan, please consult the LIVTENCITY Japan Package
Insert.
For the European Union, please consult the Summary of
Products Characteristics (SmPC).
For China, please consult the LIVTENCITY China Package
Leaflet.
For full U.S. Prescribing Information, including the approved
indication and important safety information, please visit:
https://content.takeda.com/?contenttype=pi&product=liv&language=eng&country=usa&documentnumber=1
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” 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; competitive pressures
and developments; changes to applicable laws and regulations,
including global health care reforms; 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, on Takeda and
its customers and suppliers, including foreign governments in
countries in which Takeda operates, or on other facets of its
business; the timing and impact of post-merger integration efforts
with acquired companies; the ability to divest assets that are not
core to Takeda’s operations and the timing of any such
divestment(s); 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.
* Including a subgroup with genotypic resistance to alternative
antiviral treatments. a Defined as confirmed CMV DNA concentration
below the lower limit of quantification (<LLOQ; i.e., <137
IU/mL) in two consecutive samples separated by at least five days.
b Defined as confirmed CMV DNA concentration below the lower limit
of quantification (<LLOQ; i.e., <34.5 IU/mL) in two
consecutive samples separated by at least five days. c Defined as
> 15 years old † CMV infection symptom control was defined as
resolution or improvement of tissue-invasive disease or CMV
syndrome for symptomatic patients at baseline, or no new symptoms
for patients who were asymptomatic at baseline.
References
- Avram S, et al. Novel drug targets in 2021. Nature Reviews Drug
Discovery. 2022;21(5):328-328.
- Ramanan P, Razonable RR. Cytomegalovirus infections in solid
organ transplantation: a review. Infection & Chemotherapy.
2013;45(3):260
- Camargo JF, Komanduri KV. Emerging concepts in cytomegalovirus
infection following hematopoietic stem cell transplantation.
Hematol Oncol Stem Cell Ther. 2017;10(4):233-238.
doi:10.1016/j.hemonc.2017.05.001
- LIVTENCITY Package Insert in Japan.
- Avery R, Alain S, Alexander BD, et al. SOLSTICE Trial
Investigators. Maribavir for refractory cytomegalovirus infections
with or without resistance post-transplant: results from a phase 3
randomized clinical trial. Clin Infect Dis. 2022;75(4):690–701.
doi:10.1093/cid/ciab988
- de la Hoz RE, Stephanie G, Sherlock C. Diagnosis and treatment
approaches to CMV infections in adult patients. J Clin Virol.
2002;25(Suppl 1):S1-S12. doi:10.1016/s1386-6532(02)00091-4
- Azevedo LS, Pierrotti LC, Abdala E, et al. Cytomegalovirus
infection in transplant recipients. Clinics (Sao Paolo).
2015;70(7):515-523. doi:10.6061/clinics/2015(07)09
- Styczynski J. Who is the patient at risk of CMV recurrence: a
review of the current scientific evidence with a focus on
hematopoietic cell transplantation. Infect Dis Ther. 2018;(7):1-16.
doi:10.1007/s40121-017-0180-z
View source
version on businesswire.com: https://www.businesswire.com/news/home/20240624910432/en/
International Media Rand Walton
rand.walton@takeda.com
Japan Media Shigeyuki Matsui
shigeyuki.matsui@takeda.com
Takeda Pharmaceutical (NYSE:TAK)
Historical Stock Chart
From May 2024 to Jun 2024
Takeda Pharmaceutical (NYSE:TAK)
Historical Stock Chart
From Jun 2023 to Jun 2024