Acceptance based on objective response rate
data from the Phase 2 LITESPARK-015 trial evaluating WELIREG in
certain patients with advanced PPGL
If approved, WELIREG would be the only
available therapy in the U.S. for eligible patients with advanced
PPGL
Merck (NYSE: MRK), known as MSD outside of the United States and
Canada, today announced the U.S. Food and Drug Administration (FDA)
has accepted for priority review a supplemental new drug
application (sNDA) seeking approval of WELIREG® (belzutifan),
Merck’s oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor,
for the treatment of adult and pediatric patients (12 years and
older) with advanced, unresectable, or metastatic pheochromocytoma
and paraganglioma (PPGL). The sNDA is based on objective response
rate (ORR) and duration of response (DOR) data from the Phase 2
LITESPARK-015 trial, which will be presented at an upcoming medical
meeting. The FDA has set a Prescription Drug User Fee Act (PDUFA),
or target action, date of May 26, 2025.
“Pheochromocytoma and paraganglioma are rare tumors that form in
and around the adrenal glands, and currently, there are no approved
therapies available in the U.S. for patients with this rare
disease,” said Dr. Marjorie Green, senior vice president and head
of oncology, global clinical development, Merck Research
Laboratories. “Today’s U.S. filing acceptance demonstrates our
commitment to advancing novel therapies, such as WELIREG, to help
treat patients with certain rare oncologic diseases. We look
forward to working with the FDA to potentially provide this
critical option to these patients who urgently need new innovative
therapies.”
WELIREG is the first and only HIF-2α inhibitor therapy approved
in the U.S. for the treatment of adult patients with von
Hippel-Lindau (VHL) disease who require therapy for associated
renal cell carcinoma (RCC), central nervous system
hemangioblastomas, or pancreatic neuroendocrine tumors (pNETs) not
requiring immediate surgery, based on results from the Phase 2
LITESPARK-004 trial. WELIREG is also approved for certain adult
patients with VHL disease-associated tumors in China and 16
additional countries around the world.
WELIREG is also approved in the U.S. and Canada for the
treatment of adult patients with advanced RCC following a
PD-1/PD-L1 inhibitor and a vascular endothelial growth factor
tyrosine kinase inhibitor (VEGF-TKI), based on results from the
Phase 3 LITESPARK-005 trial.
Merck is investigating WELIREG in rare oncologic diseases, RCC
and other tumor types through a broad clinical development program,
including in Phase 2 and 3 trials evaluating WELIREG as monotherapy
and in combination with other medicines.
About LITESPARK-015
LITESPARK-015 is an open-label, single-arm, multi-cohort Phase 2
trial (NCT04924075) evaluating the efficacy and safety of WELIREG
monotherapy in patients with advanced PPGL (Cohort A1), pNETs
(Cohort A2), VHL disease-associated tumors (Cohort B1), advanced
gastrointestinal stromal tumors (Cohort C), or advanced solid
tumors with HIF-2α-related genetic alterations (Cohort D). The
primary endpoint is ORR per Response Evaluation Criteria in Solid
Tumors version 1.1 (RECIST v1.1) as assessed by blinded independent
central review (BICR). Secondary endpoints include DOR, time to
response, disease control, progression-free survival, overall
survival and safety. The trial enrolled an estimated 322 patients
who received WELIREG 120 mg orally once daily.
About pheochromocytoma and paraganglioma
Pheochromocytoma and paraganglioma (PPGL) are rare adrenal
tumors that can be caused by certain genetic syndromes or
mutations. It is estimated that up to 2,000 new cases of PPGL are
diagnosed each year in the U.S., and up to 52,800 new cases are
diagnosed each year worldwide. Pheochromocytoma occur in the center
of the adrenal gland, whereas paraganglioma occur in nerve tissue
in the adrenal glands and near certain blood vessels and nerves. Up
to 25% of PPGL cases are metastatic at diagnosis.
About WELIREG® (belzutifan) 40 mg tablets, for oral
use
Indications in the U.S.
Certain von Hippel-Lindau (VHL) disease-associated tumors
WELIREG (belzutifan) is indicated for the treatment of adult
patients with von Hippel-Lindau (VHL) disease who require therapy
for associated renal cell carcinoma (RCC), central nervous system
(CNS) hemangioblastomas, or pancreatic neuroendocrine tumors
(pNET), not requiring immediate surgery.
Advanced Renal Cell Carcinoma (RCC)
WELIREG is indicated for the treatment of adult patients with
advanced renal cell carcinoma (RCC) following a programmed death
receptor-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor
and a vascular endothelial growth factor tyrosine kinase inhibitor
(VEGF-TKI).
Selected Safety Information for WELIREG
Warning: Embryo-Fetal Toxicity
Exposure to WELIREG during pregnancy can cause embryo-fetal
harm. Verify pregnancy status prior to the initiation of WELIREG.
Advise patients of these risks and the need for effective
non-hormonal contraception as WELIREG can render some hormonal
contraceptives ineffective.
Anemia
WELIREG can cause severe anemia that can require blood
transfusion. Monitor for anemia before initiation of, and
periodically throughout, treatment. Transfuse patients as
clinically indicated. For patients with hemoglobin <8 g/dL,
withhold WELIREG until ≥8 g/dL, then resume at the same or reduced
dose or permanently discontinue WELIREG, depending on the severity
of anemia. For life-threatening anemia or when urgent intervention
is indicated, withhold WELIREG until hemoglobin ≥8 g/dL, then
resume at a reduced dose or permanently discontinue WELIREG.
In LITESPARK-004 (N=61), decreased hemoglobin occurred in 93% of
patients with VHL disease and 7% had Grade 3 events. Median time to
onset of anemia was 31 days (range: 1 day to 8.4 months).
The safety of erythropoiesis-stimulating agents (ESAs) for
treatment of anemia in patients with VHL disease treated with
WELIREG has not been established.
In LITESPARK-005 (n=372), decreased hemoglobin occurred in 88%
of patients with advanced RCC and 29% had Grade 3 events. Median
time to onset of anemia was 29 days (range: 1 day to 16.6 months).
Of the patients with anemia, 22% received transfusions only, 20%
received ESAs only, and 12% received both transfusion and ESAs.
Hypoxia
WELIREG can cause severe hypoxia that may require
discontinuation, supplemental oxygen, or hospitalization.
Monitor oxygen saturation before initiation of, and periodically
throughout, treatment. For decreased oxygen saturation with
exercise (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg), consider
withholding WELIREG until pulse oximetry with exercise is greater
than 88%, then resume at the same or a reduced dose. For decreased
oxygen saturation at rest (e.g., pulse oximeter <88% or PaO2 ≤55
mm Hg) or when urgent intervention is indicated, withhold WELIREG
until resolved and resume at a reduced dose or discontinue. For
life-threatening or recurrent symptomatic hypoxia, permanently
discontinue WELIREG. Advise patients to report signs and symptoms
of hypoxia immediately to a healthcare provider.
In LITESPARK-004, hypoxia occurred in 1.6% of patients.
In LITESPARK-005, hypoxia occurred in 15% of patients and 10%
had Grade 3 events. Of the patients with hypoxia, 69% were treated
with oxygen therapy. Median time to onset of hypoxia was 30.5 days
(range: 1 day to 21.1 months).
Embryo-Fetal Toxicity
Based on findings in animals, WELIREG can cause fetal harm when
administered to a pregnant woman.
Advise pregnant women and females of reproductive potential of
the potential risk to the fetus. Advise females of reproductive
potential to use effective non-hormonal contraception during
treatment with WELIREG and for 1 week after the last dose. WELIREG
can render some hormonal contraceptives ineffective. Advise male
patients with female partners of reproductive potential to use
effective contraception during treatment with WELIREG and for 1
week after the last dose.
Adverse Reactions
In LITESPARK-004, serious adverse reactions occurred in 15% of
patients, including anemia, hypoxia, anaphylaxis reaction, retinal
detachment, and central retinal vein occlusion (1 patient
each).
WELIREG was permanently discontinued due to adverse reactions in
3.3% of patients for dizziness and opioid overdose (1.6% each).
Dosage interruptions due to an adverse reaction occurred in 39%
of patients. Those which required dosage interruption in >2% of
patients were fatigue, decreased hemoglobin, anemia, nausea,
abdominal pain, headache, and influenza-like illness.
Dose reductions due to an adverse reaction occurred in 13% of
patients. The most frequently reported adverse reaction which
required dose reduction was fatigue (7%).
The most common adverse reactions (≥25%), including laboratory
abnormalities, that occurred in patients who received WELIREG were
decreased hemoglobin (93%), fatigue (64%), increased creatinine
(64%), headache (39%), dizziness (38%), increased glucose (34%),
and nausea (31%).
In LITESPARK-005, serious adverse reactions occurred in 38% of
patients. The most frequently reported serious adverse reactions
were hypoxia (7%), anemia (5%), pneumonia (3.5%), hemorrhage (3%),
and pleural effusion (2.2%). Fatal adverse reactions occurred in
3.2% of patients who received WELIREG, including sepsis (0.5%) and
hemorrhage (0.5%).
WELIREG was permanently discontinued due to adverse reactions in
6% of patients. Adverse reactions which resulted in permanent
discontinuation (≥0.5%) were hypoxia (1.1%) and hemorrhage
(0.5%).
Dosage interruptions due to an adverse reaction occurred in 39%
of patients. Of the patients who received WELIREG, 28% were 65 to
74 years, and 10% were 75 years and over. Dose interruptions
occurred in 48% of patients ≥65 years of age and in 34% of younger
patients. Adverse reactions which required dosage interruption in
≥2% of patients were anemia (8%), hypoxia (5%), COVID-19 (4.3%),
fatigue (3.2%), and hemorrhage (2.2%).
Dose reductions due to an adverse reaction occurred in 13% of
patients. Dose reductions occurred in 18% of patients ≥65 years of
age and in 10% of younger patients. The most frequently reported
adverse reactions which required dose reduction (≥1.0%) were
hypoxia (5%) and anemia (3.2%).
The most common (≥25%) adverse reactions, including laboratory
abnormalities, were decreased hemoglobin (88%), fatigue (43%),
musculoskeletal pain (33%), increased creatinine (34%), decreased
lymphocytes (34%), increased alanine aminotransferase (32%),
decreased sodium (31%), increased potassium (29%), and increased
aspartate aminotransferase (27%).
Drug Interactions
Coadministration of WELIREG with inhibitors of UGT2B17 or
CYP2C19 increases plasma exposure of belzutifan, which may increase
the incidence and severity of adverse reactions. Monitor for anemia
and hypoxia and reduce the dosage of WELIREG as recommended.
Coadministration of WELIREG with CYP3A4 substrates decreases
concentrations of CYP3A4 substrates, which may reduce the efficacy
of these substrates or lead to therapeutic failures. Avoid
coadministration with sensitive CYP3A4 substrates. If
coadministration cannot be avoided, increase the sensitive CYP3A4
substrate dosage in accordance with its Prescribing Information.
Coadministration of WELIREG with hormonal contraceptives may lead
to contraceptive failure or an increase in breakthrough
bleeding.
Lactation
Because of the potential for serious adverse reactions in
breastfed children, advise women not to breastfeed during treatment
with WELIREG and for 1 week after the last dose.
Females and Males of Reproductive Potential
WELIREG can cause fetal harm when administered to a pregnant
woman. Verify the pregnancy status of females of reproductive
potential prior to initiating treatment with WELIREG.
Use of WELIREG may reduce the efficacy of hormonal
contraceptives. Advise females of reproductive potential to use
effective non-hormonal contraception during treatment with WELIREG
and for 1 week after the last dose. Advise males with female
partners of reproductive potential to use effective contraception
during treatment with WELIREG and for 1 week after the last
dose.
Based on findings in animals, WELIREG may impair fertility in
males and females of reproductive potential and the reversibility
of this effect is unknown.
Pediatric Use
Safety and effectiveness of WELIREG in pediatric patients under
18 years of age have not been established.
Merck’s focus on cancer
Every day, we follow the science as we work to discover
innovations that can help patients, no matter what stage of cancer
they have. As a leading oncology company, we are pursuing research
where scientific opportunity and medical need converge, underpinned
by our diverse pipeline of more than 25 novel mechanisms. With one
of the largest clinical development programs across more than 30
tumor types, we strive to advance breakthrough science that will
shape the future of oncology. By addressing barriers to clinical
trial participation, screening and treatment, we work with urgency
to reduce disparities and help ensure patients have access to
high-quality cancer care. Our unwavering commitment is what will
bring us closer to our goal of bringing life to more patients with
cancer. For more information, visit
https://www.merck.com/research/oncology.
About Merck
At Merck, known as MSD outside of the United States and Canada,
we are unified around our purpose: We use the power of leading-edge
science to save and improve lives around the world. For more than
130 years, we have brought hope to humanity through the development
of important medicines and vaccines. We aspire to be the premier
research-intensive biopharmaceutical company in the world – and
today, we are at the forefront of research to deliver innovative
health solutions that advance the prevention and treatment of
diseases in people and animals. We foster a diverse and inclusive
global workforce and operate responsibly every day to enable a
safe, sustainable and healthy future for all people and
communities. For more information, visit www.merck.com and connect
with us X (formerly Twitter), Facebook, Instagram, YouTube and
LinkedIn.
Forward-Looking Statement of Merck & Co., Inc., Rahway,
N.J., USA
This news release of Merck & Co., Inc., Rahway, N.J., USA
(the “company”) includes “forward-looking statements” within the
meaning of the safe harbor provisions of the U.S. Private
Securities Litigation Reform Act of 1995. These statements are
based upon the current beliefs and expectations of the company’s
management and are subject to significant risks and uncertainties.
There can be no guarantees with respect to pipeline candidates that
the candidates will receive the necessary regulatory approvals or
that they will prove to be commercially successful. If underlying
assumptions prove inaccurate or risks or uncertainties materialize,
actual results may differ materially from those set forth in the
forward-looking statements.
Risks and uncertainties include but are not limited to, general
industry conditions and competition; general economic factors,
including interest rate and currency exchange rate fluctuations;
the impact of pharmaceutical industry regulation and health care
legislation in the United States and internationally; global trends
toward health care cost containment; technological advances, new
products and patents attained by competitors; challenges inherent
in new product development, including obtaining regulatory
approval; the company’s ability to accurately predict future market
conditions; manufacturing difficulties or delays; financial
instability of international economies and sovereign risk;
dependence on the effectiveness of the company’s patents and other
protections for innovation products; and the exposure to
litigation, including patent litigation, and/or regulatory
actions.
The company undertakes no obligation to publicly update any
forward-looking statement, whether as a result of new information,
future events or otherwise. Additional factors that could cause
results to differ materially from those described in the
forward-looking statements can be found in the company’s Annual
Report on Form 10-K for the year ended December 31, 2023 and the
company’s other filings with the Securities and Exchange Commission
(SEC) available at the SEC’s Internet site (www.sec.gov).
Please see Prescribing Information, including information for
the Boxed Warning about embryo-fetal toxicity, for WELIREG
(belzutifan) at
https://www.merck.com/product/usa/pi_circulars/w/welireg/welireg_pi.pdf
and Medication Guide for WELIREG at
https://www.merck.com/product/usa/pi_circulars/w/welireg/welireg_mg.pdf.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20250127087005/en/
Media Contacts: Julie Cunningham (617) 519-6264 Michael McArdle
(908) 447-9453 Investor Contacts: Peter Dannenbaum (732) 594-1579
Steven Graziano (732) 594-1583
Merck (NYSE:MRK)
Historical Stock Chart
From Feb 2025 to Mar 2025
Merck (NYSE:MRK)
Historical Stock Chart
From Mar 2024 to Mar 2025
