Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the
U.S. Food and Drug Administration (FDA) has granted Breakthrough
Therapy Designation to Trodelvy® (sacituzumab govitecan-hziy) for
the treatment of adult patients with extensive-stage small cell
lung cancer (ES-SCLC) whose disease has progressed on or after
platinum-based chemotherapy.
The Breakthrough Therapy Designation is based on results from
the global Phase 2 TROPiCS-03 study ES-SCLC cohort, which showed
encouraging results with Trodelvy as a second-line treatment for
ES-SCLC. As recently presented at the IASLC 2024 World Conference
on Lung Cancer, Trodelvy demonstrated promising antitumor activity
in both platinum-resistant (PR) and platinum-sensitive (PS)
disease, and the safety profile was consistent with previous
Trodelvy studies. These data support further investigation of
Trodelvy in ES-SCLC and Gilead plans to initiate a Phase 3 clinical
trial in this patient population.
Lung cancer is the second most diagnosed cancer in the U.S., and
the leading cause of cancer-related deaths. Approximately 15% of
lung cancer cases are SCLC, with nearly 70% of patients with SCLC
diagnosed at extensive-stage, which occurs when the cancer has
spread to both lungs or beyond the lungs to lymph nodes or other
organs. For people with ES-SCLC whose disease does not respond to
current first-line standard of care (platinum-based chemotherapy or
immunotherapy), the prognosis is often poor, and treatment options
are limited. There is an urgent need for new and more effective
approaches to care that can improve survival and slow the
progression of the disease.
Breakthrough Therapy Designation is designed to expedite the
development and regulatory review of investigational treatments for
serious or life-threatening conditions that, based on preliminary
clinical evidence, have the potential to substantially improve
clinical outcomes compared with available therapy. This is the
second Breakthrough Therapy Designation for Trodelvy.
Trodelvy is the first and only approved Trop-2-directed
antibody-drug conjugate (ADC) that has demonstrated meaningful
survival advantages in two different types of metastatic breast
cancers. Across Phase 3 trials, we are exploring Trodelvy alone or
in combination with other agents across many diverse tumor types
and stages of disease. This includes collaborations with partners
in academia, industry and the global cancer community.
About Trodelvy
Trodelvy® (sacituzumab govitecan-hziy) is a first-in-class
Trop-2-directed antibody-drug conjugate. Trop-2 is a cell surface
antigen highly expressed in multiple tumor types, including in more
than 90% of breast and lung cancers. Trodelvy is intentionally
designed with a proprietary hydrolyzable linker attached to SN-38,
a topoisomerase I inhibitor payload. This unique combination
delivers potent activity to both Trop-2 expressing cells and the
tumor microenvironment through a bystander effect.
Trodelvy is currently approved in more than 50 countries for
second-line or later metastatic triple-negative breast cancer
(TNBC) patients and in more than 40 countries for certain patients
with pre-treated HR+/HER2- metastatic breast cancer.
Trodelvy is being investigated for use in other TNBC and
HR+/HER2- breast cancer populations, as well as a range of tumor
types where Trop-2 is highly expressed, including small cell lung
cancer and first-line metastatic non-small cell lung cancer where
Trodelvy has shown clinical activity through the TROPiCS-03
proof-of-concept study and the EVOKE-02 proof-of-concept study,
respectively. Trodelvy is also being studied in head and neck
cancer and gynecological cancers.
U.S. Indications for Trodelvy
In the United States, Trodelvy is indicated for the treatment of
adult patients with:
- Unresectable locally advanced or metastatic triple-negative
breast cancer (mTNBC) who have received two or more prior systemic
therapies, at least one of them for metastatic disease.
- Unresectable locally advanced or metastatic hormone receptor
(HR)-positive, human epidermal growth factor receptor 2
(HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who
have received endocrine-based therapy and at least two additional
systemic therapies in the metastatic setting.
U.S. Important Safety Information for Trodelvy
BOXED WARNING: NEUTROPENIA AND DIARRHEA
- Severe or life-threatening neutropenia may occur. Withhold
Trodelvy for absolute neutrophil count below 1500/mm3 or
neutropenic fever. Monitor blood cell counts periodically during
treatment. Consider G-CSF for secondary prophylaxis. Initiate
anti-infective treatment in patients with febrile neutropenia
without delay.
- Severe diarrhea may occur. Monitor patients with diarrhea
and give fluid and electrolytes as needed. At the onset of
diarrhea, evaluate for infectious causes and, if negative, promptly
initiate loperamide. If severe diarrhea occurs, withhold Trodelvy
until resolved to ≤Grade 1 and reduce subsequent doses.
CONTRAINDICATIONS
- Severe hypersensitivity reaction to Trodelvy.
WARNINGS AND PRECAUTIONS
Neutropenia: Severe, life-threatening, or fatal
neutropenia can occur and may require dose modification.
Neutropenia occurred in 64% of patients treated with Trodelvy.
Grade 3-4 neutropenia occurred in 49% of patients. Febrile
neutropenia occurred in 6%. Neutropenic colitis occurred in 1.4%.
Withhold Trodelvy for absolute neutrophil count below 1500/mm3 on
Day 1 of any cycle or neutrophil count below 1000/mm3 on Day 8 of
any cycle. Withhold Trodelvy for neutropenic fever. Administer
G-CSF as clinically indicated or indicated in Table 1 of USPI.
Diarrhea: Diarrhea occurred in 64% of all patients
treated with Trodelvy. Grade 3-4 diarrhea occurred in 11% of
patients. One patient had intestinal perforation following
diarrhea. Diarrhea that led to dehydration and subsequent acute
kidney injury occurred in 0.7% of all patients. Withhold Trodelvy
for Grade 3-4 diarrhea and resume when resolved to ≤Grade 1. At
onset, evaluate for infectious causes and if negative, promptly
initiate loperamide, 4 mg initially followed by 2 mg with every
episode of diarrhea for a maximum of 16 mg daily. Discontinue
loperamide 12 hours after diarrhea resolves. Additional supportive
measures (e.g., fluid and electrolyte substitution) may also be
employed as clinically indicated. Patients who exhibit an excessive
cholinergic response to treatment can receive appropriate
premedication (e.g., atropine) for subsequent treatments.
Hypersensitivity and Infusion-Related Reactions: Serious
hypersensitivity reactions including life-threatening anaphylactic
reactions have occurred with Trodelvy. Severe signs and symptoms
included cardiac arrest, hypotension, wheezing, angioedema,
swelling, pneumonitis, and skin reactions. Hypersensitivity
reactions within 24 hours of dosing occurred in 35% of patients.
Grade 3-4 hypersensitivity occurred in 2% of patients. The
incidence of hypersensitivity reactions leading to permanent
discontinuation of Trodelvy was 0.2%. The incidence of anaphylactic
reactions was 0.2%. Pre-infusion medication is recommended. Have
medications and emergency equipment to treat such reactions
available for immediate use. Observe patients closely for
hypersensitivity and infusion-related reactions during each
infusion and for at least 30 minutes after completion of each
infusion. Permanently discontinue Trodelvy for Grade 4
infusion-related reactions.
Nausea and Vomiting: Nausea occurred in 64% of all
patients treated with Trodelvy and Grade 3-4 nausea occurred in 3%
of these patients. Vomiting occurred in 35% of patients and Grade
3-4 vomiting occurred in 2% of these patients. Premedicate with a
two or three drug combination regimen (e.g., dexamethasone with
either a 5-HT3 receptor antagonist or an NK1 receptor antagonist as
well as other drugs as indicated) for prevention of
chemotherapy-induced nausea and vomiting (CINV). Withhold Trodelvy
doses for Grade 3 nausea or Grade 3-4 vomiting and resume with
additional supportive measures when resolved to Grade ≤1.
Additional antiemetics and other supportive measures may also be
employed as clinically indicated. All patients should be given
take-home medications with clear instructions for prevention and
treatment of nausea and vomiting.
Increased Risk of Adverse Reactions in Patients with Reduced
UGT1A1 Activity: Patients homozygous for the uridine
diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at
increased risk for neutropenia, febrile neutropenia, and anemia and
may be at increased risk for other adverse reactions with Trodelvy.
The incidence of Grade 3-4 neutropenia was 58% in patients
homozygous for the UGT1A1*28, 49% in patients heterozygous for the
UGT1A1*28 allele, and 43% in patients homozygous for the wild-type
allele. The incidence of Grade 3-4 anemia was 21% in patients
homozygous for the UGT1A1*28 allele, 10% in patients heterozygous
for the UGT1A1*28 allele, and 9% in patients homozygous for the
wild-type allele. Closely monitor patients with known reduced
UGT1A1 activity for adverse reactions. Withhold or permanently
discontinue Trodelvy based on clinical assessment of the onset,
duration and severity of the observed adverse reactions in patients
with evidence of acute early-onset or unusually severe adverse
reactions, which may indicate reduced UGT1A1 function.
Embryo-Fetal Toxicity: Based on its mechanism of action,
Trodelvy can cause teratogenicity and/or embryo-fetal lethality
when administered to a pregnant woman. Trodelvy contains a
genotoxic component, SN-38, and targets rapidly dividing cells.
Advise pregnant women and females of reproductive potential of the
potential risk to a fetus. Advise females of reproductive potential
to use effective contraception during treatment with Trodelvy and
for 6 months after the last dose. Advise male patients with female
partners of reproductive potential to use effective contraception
during treatment with Trodelvy and for 3 months after the last
dose.
ADVERSE REACTIONS
In the pooled safety population, the most common (≥ 25%) adverse
reactions including laboratory abnormalities were decreased
leukocyte count (84%), decreased neutrophil count (75%), decreased
hemoglobin (69%), diarrhea (64%), nausea (64%), decreased
lymphocyte count (63%), fatigue (51%), alopecia (45%), constipation
(37%), increased glucose (37%), decreased albumin (35%), vomiting
(35%), decreased appetite (30%), decreased creatinine clearance
(28%), increased alkaline phosphatase (28%), decreased magnesium
(27%), decreased potassium (26%), and decreased sodium (26%).
In the ASCENT study (locally advanced or metastatic
triple-negative breast cancer), the most common adverse reactions
(incidence ≥25%) were fatigue, diarrhea, nausea, alopecia,
constipation, vomiting, abdominal pain, and decreased appetite. The
most frequent serious adverse reactions (SAR) (>1%) were
neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were
reported in 27% of patients, and 5% discontinued therapy due to
adverse reactions. The most common Grade 3-4 lab abnormalities
(incidence ≥25%) in the ASCENT study were reduced neutrophils,
leukocytes, and lymphocytes.
In the TROPiCS-02 study (locally advanced or metastatic
HR-positive, HER2-negative breast cancer), the most common adverse
reactions (incidence ≥25%) were diarrhea, fatigue, nausea,
alopecia, and constipation. The most frequent serious adverse
reactions (SAR) (>1%) were diarrhea (5%), febrile neutropenia
(4%), neutropenia (3%), abdominal pain, colitis, neutropenic
colitis, pneumonia, and vomiting (each 2%). SAR were reported in
28% of patients, and 6% discontinued therapy due to adverse
reactions. The most common Grade 3-4 lab abnormalities (incidence
≥25%) in the TROPiCS-02 study were reduced neutrophils and
leukocytes.
DRUG INTERACTIONS
UGT1A1 Inhibitors: Concomitant administration of Trodelvy
with inhibitors of UGT1A1 may increase the incidence of adverse
reactions due to potential increase in systemic exposure to SN-38.
Avoid administering UGT1A1 inhibitors with Trodelvy.
UGT1A1 Inducers: Exposure to SN-38 may be reduced in
patients concomitantly receiving UGT1A1 enzyme inducers. Avoid
administering UGT1A1 inducers with Trodelvy.
Please see full Prescribing Information,
including BOXED WARNING.
About Gilead Sciences
Gilead Sciences, Inc. is a biopharmaceutical company that has
pursued and achieved breakthroughs in medicine for more than three
decades, with the goal of creating a healthier world for all
people. The company is committed to advancing innovative medicines
to prevent and treat life-threatening diseases, including HIV,
viral hepatitis, COVID-19, cancer, and inflammation. Gilead
operates in more than 35 countries worldwide, with headquarters in
Foster City, Calif.
Forward-Looking
Statement
This press release includes forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of 1995
that are subject to risks, uncertainties and other factors,
including Gilead’s ability to initiate, progress or complete
clinical trials or studies within currently anticipated timelines
or at all, and the possibility of unfavorable results from ongoing
and additional clinical trials or studies, including those
involving Trodelvy (such as TROPiCS-03); uncertainties relating to
regulatory applications and related filing and approval timelines,
including potential applications for programs and/or indications
currently under evaluation; the possibility that Gilead may make a
strategic decision to discontinue development of these programs
and, as a result, these programs may never be successfully
commercialized for the indications currently under evaluation; and
any assumptions underlying any of the foregoing. These and other
risks, uncertainties and factors are described in detail in
Gilead’s Quarterly Report on Form 10-Q for the quarter ended
September 30, 2024, as filed with the U.S. Securities and Exchange
Commission. These risks, uncertainties and other factors could
cause actual results to differ materially from those referred to in
the forward-looking statements. All statements other than
statements of historical fact are statements that could be deemed
forward-looking statements. The reader is cautioned that any such
forward-looking statements are not guarantees of future performance
and involve risks and uncertainties and is cautioned not to place
undue reliance on these forward-looking statements. All
forward-looking statements are based on information currently
available to Gilead, and Gilead assumes no obligation and disclaims
any intent to update any such forward-looking statements.
Trodelvy, Gilead and the Gilead logo are
trademarks of Gilead Sciences, Inc., or its related companies.
U.S. Prescribing Information for Trodelvy,
including BOXED WARNING, is available at www.gilead.com.
For more information about Gilead, please visit
the company’s website at www.gilead.com, follow Gilead on X/Twitter
(@GileadSciences) and LinkedIn (@Gilead-Sciences).
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version on businesswire.com: https://www.businesswire.com/news/home/20241216528668/en/
Blair Baumwell, Media public_affairs@gilead.com
Jacquie Ross, Investors investor_relations@gilead.com
Gilead Sciences (NASDAQ:GILD)
過去 株価チャート
から 12 2024 まで 1 2025
Gilead Sciences (NASDAQ:GILD)
過去 株価チャート
から 1 2024 まで 1 2025
