UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
Form 6-K
REPORT OF FOREIGN PRIVATE ISSUER PURSUANT TO RULE 13a-16 OR
15d-16
UNDER THE SECURITIES EXCHANGE ACT OF 1934
For the
month of April 2020
Commission
File Number 001-15170
GlaxoSmithKline plc
(Translation
of registrant's name into English)
980 Great West Road, Brentford, Middlesex, TW8 9GS
(Address
of principal executive office)
Indicate
by check mark whether the registrant files or will file annual
reports under cover of Form 20-F or Form 40-F.
Form
20-F . . . .X. . . . Form 40-F . . . . . . . .
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by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(1): ____
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by check mark if the registrant is submitting the Form 6-K in paper
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Issued: 29 April 2020, London UK - LSE announcement
FDA approves Zejula (niraparib) as the only once-daily PARP
inhibitor in first-line monotherapy maintenance treatment for women
with platinum-responsive advanced ovarian cancer regardless of
biomarker status
●
Zejula is the only oral
monotherapy available as first-line maintenance treatment for women
regardless of BRCA mutational status, addressing a high unmet
need in ovarian cancer
● New individualised starting dose based on the
patient's baseline weight and/or platelet count approved for
first-line maintenance treatment; lower rates of haematological
adverse events were observed with the individualised dosing
group
●
The supplemental New
Drug Application was approved under the FDA's Real-Time Oncology
Review pilot program
GlaxoSmithKline plc (LSE/NYSE: GSK) today announced the US Food and
Drug Administration (FDA) approved the company's supplemental New
Drug Application (sNDA) for Zejula (niraparib), an oral,
once-daily poly (ADP-ribose) polymerase (PARP) inhibitor, as a
monotherapy maintenance treatment for women with advanced
epithelial ovarian, fallopian tube, or primary peritoneal cancer
who are in a complete or partial response to first-line
platinum-based chemotherapy, regardless of biomarker
status. Until now, only 20% of women with ovarian cancer,
those with a BRCA mutation (BRCAm), were eligible to be treated with a PARP
inhibitor as monotherapy in the first-line maintenance
setting.[i]
Dr. Hal
Barron, Chief Scientific Officer and President R&D, GSK,
said: "Women with advanced
ovarian cancer have a five-year survival rate of less than 50%.
This expanded indication means that many more women with this
devastating disease can receive earlier treatment with Zejula,
which can extend the time it takes for their cancer to
progress."
Zejula is the only once-daily PARP inhibitor approved in the US as
monotherapy for women with advanced ovarian cancer beyond those
with BRCAm disease in the first-line and recurrent
maintenance treatment settings, as well as late-line primary
treatment settings.
This new indication is supported by data from the phase III PRIMA
study (ENGOT-OV26/GOG-3012), which enrolled
patients with newly
diagnosed advanced ovarian cancer
following a complete or partial response to platinum-based
chemotherapy regardless of
biomarker status. The
PRIMA study enrolled women who had higher risk of disease
progression, a population with high unmet needs and limited
treatment options.
Dr. Bradley Monk, PRIMA investigator, US Oncology, University of
Arizona College of Medicine, Phoenix Creighton University School of
Medicine at St. Joseph's Hospital Phoenix, said: "PRIMA was
designed for patients with ovarian cancer who have a high unmet
need. The positive data observed regardless of biomarker status in
this study is extremely encouraging and suggests benefit beyond
the BRCAm population. This approval is an
important step forward in the treatment of ovarian cancer. In my
opinion, maintenance treatment with niraparib should be considered
an option for appropriate patients who responded to first-line
platinum-based chemotherapy versus active
surveillance."
The primary endpoint in the PRIMA study was progression-free
survival (PFS) analysed sequentially, first in the homologous
recombination deficient (HRd) population, then in the overall
population. The PRIMA study significantly improved PFS for patients
treated with Zejula, regardless of biomarker status. In the HRd
population, Zejula resulted in a 57% reduction in the risk of
disease progression or death vs. placebo (HR 0.43; 95% CI, 0.31 to
0.59; p<0.0001), and a 38% reduction in the risk of disease
progression or death vs. placebo in the overall population (HR
0.62; 95% CI, 0.50 to 0.76; p<0.0001).
Zejula's safety profile, as demonstrated by the PRIMA results, was
consistent with clinical trial experience. The most common grade 3
or higher adverse events with Zejula included thrombocytopenia
(39%), anaemia (31%) and neutropenia (21%).
At initiation of the PRIMA study, patients received a fixed
starting dose of 300 mg of Zejula once-daily. The study was later
amended to incorporate an individualised starting dose of either
200 mg or 300 mg of Zejula once-daily based on the patient's
baseline weight and/or platelet count. Lower rates of grade 3 and 4
haematologic treatment-emergent adverse events were observed with
an individualised starting dose, compared to the overall
population, including thrombocytopenia (21% compared to 39%),
anaemia (23% compared to 31%) and neutropenia (15% compared to
21%).
The Zejula US prescribing information has been updated to include
the individualised starting dose of 200 mg or 300
mg once-daily based on patients' baseline weight and/or
platelet count for the first-line maintenance treatment indication.
The starting dose for recurrent ovarian cancer and late-line
treatment settings is 300 mg once-daily.
"It's so important for patients with ovarian cancer to have
treatment options, and this approval is positive news for our
community," said Audra Moran, President and CEO, Ovarian Cancer
Research Alliance. "PARP inhibitors represent a major advancement
in the fight against ovarian cancer, and having a new first-line
maintenance option for platinum-responsive advanced ovarian cancer
patients - regardless of BRCA mutation status - is especially exciting. We
are determined to keep funding research and partnering with
scientists who are on the frontline of finding new treatments like
this one to help those impacted by this
disease."
PRIMA study results were previously presented at the 2019 European
Society for Medical Oncology (ESMO) Congress and published in
the New
England Journal of Medicine.
Zejula is not approved for use in first-line maintenance treatment
outside the US.
About Ovarian Cancer
In the US, ovarian cancer impacts nearly 222,000 women
annually,[ii] and
it is the fifth most frequent cause of cancer death among
women.[iii] Despite
high response rates to platinum-based chemotherapy in the
front-line setting, approximately 85% of patients will experience
disease recurrence.[iv] Once
the disease recurs, it is rarely curable, with decreasing time
intervals to each subsequent recurrence.
About Zejula (niraparib)
Niraparib is an oral, once-daily PARP inhibitor that is currently
being evaluated in multiple pivotal trials. GSK is building a
robust niraparib clinical development programme by assessing
activity across multiple tumour types and by evaluating several
potential combinations of niraparib with other therapeutics. The
ongoing development programme for niraparib includes several
combination studies, including a phase III study as a first-line
triplet maintenance treatment in ovarian cancer
(FIRST).
GSK in Oncology
GSK is focused on maximising patient survival through
transformational medicines. GSK's pipeline is focused on
immuno-oncology, cell therapy, cancer epigenetics and synthetic
lethality. Our goal is to achieve a sustainable flow of new
treatments based on a diversified portfolio of investigational
medicines utilising modalities such as small molecules, antibodies,
antibody drug conjugates and cell therapy, either alone or in
combination.
Indications and Important Safety Information for
ZEJULA
Indications
ZEJULA is indicated:
●
for the maintenance treatment of adult
patients with advanced epithelial ovarian, fallopian tube, or
primary peritoneal cancer who are in a complete or partial response
to first-line platinum-based chemotherapy.
●
for the maintenance
treatment of adult patients with recurrent epithelial ovarian,
fallopian tube, or primary peritoneal cancer who are in a complete
or partial response to platinum-based
chemotherapy.
●
for the treatment of
adult patients with advanced ovarian, fallopian tube, or primary
peritoneal cancer who have been treated with three or more prior
chemotherapy regimens and whose cancer is associated with
homologous recombination deficiency (HRD) positive status defined
by either:
●
a deleterious or suspected
deleterious BRCA mutation, or
●
genomic instability and who have
progressed more than six months after response to the last
platinum-based chemotherapy.
Select
patients for therapy based on an FDA-approved companion diagnostic
for ZEJULA.
Important Safety Information
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML), including some fatal cases, was
reported in 15 patients (0.8%) out of 1785 patients treated with
ZEJULA monotherapy in clinical trials. The duration of therapy in
patients who developed secondary MDS/cancer therapy-related AML
varied from 0.5 months to 4.9 years. These patients had received
prior chemotherapy with platinum agents and/or other DNA-damaging
agents including radiotherapy. Discontinue ZEJULA if MDS/AML is
confirmed.
Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia)
have been reported in patients receiving ZEJULA. The overall
incidence of Grade ≥3 thrombocytopenia, anemia and
neutropenia were reported, respectively, in 39%, 31%, and 21% of
patients receiving ZEJULA in PRIMA; 29%, 25%, and 20% of patients
receiving ZEJULA in NOVA; and 28%, 27%, and 13% of patients
receiving ZEJULA in QUADRA. Discontinuation due to
thrombocytopenia, anemia, and neutropenia occurred, respectively,
in 4%, 2%, and 2% of patients in PRIMA; 3%, 1%, and 2% of patients
in NOVA; and 4%, 2%, and 1% of patients in QUADRA. In patients who
were administered a starting dose of ZEJULA based on baseline
weight or platelet count in PRIMA, Grade ≥3 thrombocytopenia,
anemia and neutropenia were reported, respectively, in 22%, 23%,
and 15% of patients receiving ZEJULA. Discontinuation due to
thrombocytopenia, anemia, and neutropenia occurred, respectively,
in 3%, 3%, and 2% of patients. Do not start ZEJULA until patients
have recovered from hematological toxicity caused by prior
chemotherapy (≤ Grade 1). Monitor complete blood counts
weekly for the first month, monthly for the next 11 months, and
periodically thereafter. If hematological toxicities do not resolve
within 28 days following interruption, discontinue ZEJULA, and
refer the patient to a hematologist for further
investigations.
Hypertension and hypertensive crisis have been reported in patients receiving ZEJULA.
Grade 3-4 hypertension occurred in 6% of patients receiving ZEJULA
vs 1% of patients receiving placebo in PRIMA, with no reported
discontinuations. Grade 3-4 hypertension occurred in 9% of patients
receiving ZEJULA vs 2% of patients receiving placebo in NOVA, with
discontinuation occurring in <1% of patients. Grade 3-4
hypertension occurred in 5% of ZEJULA-treated patients in QUADRA,
with discontinuation occurring in <0.2% of patients. Monitor
blood pressure and heart rate at least weekly for the first two
months, then monthly for the first year, and periodically
thereafter during treatment. Closely monitor patients with
cardiovascular disorders, especially coronary insufficiency,
cardiac arrhythmias, and hypertension. Manage hypertension with
antihypertensive medications and adjustment of the ZEJULA dose, if
necessary.
Embryo-Fetal Toxicity and Lactation: Based on its mechanism of action, ZEJULA can
cause fetal harm. Advise females of reproductive potential of the
potential risk to a fetus and to use effective contraception during
treatment and for 6 months after receiving their final dose of
ZEJULA. Because of the potential for serious adverse reactions from
ZEJULA in breastfed infants, advise lactating women to not
breastfeed during treatment with ZEJULA and for 1 month after
receiving the final dose.
First-line Maintenance Advanced Ovarian Cancer
Most common adverse reactions (Grades 1-4) in ≥10% of
all patients who received ZEJULA in PRIMA were thrombocytopenia
(66%), anemia (64%), nausea (57%), fatigue (51%), neutropenia
(42%), constipation (40%), musculoskeletal pain (39%), leukopenia
(28%), headache (26%), insomnia (25%), vomiting (22%), dyspnea
(22%), decreased appetite (19%), dizziness (19%), cough (18%),
hypertension (18%), AST/ALT elevation (14%), and acute kidney
injury (12%).
Common lab abnormalities (Grades 1-4) in ≥25% of all patients
who received ZEJULA in PRIMA included: decreased hemoglobin (87%),
decreased platelets (74%), decreased leukocytes (71%), increased
glucose (66%), decreased neutrophils (66%), decreased lymphocytes
(51%), increased alkaline phosphatase (46%), increased creatinine
(40%), decreased magnesium (36%), increased AST (35%) and increased
ALT (29%).
Maintenance Recurrent Ovarian Cancer
Most common adverse reactions (Grades 1-4) in ≥10% of
patients who received ZEJULA in NOVA were nausea (74%),
thrombocytopenia (61%), fatigue/asthenia (57%), anemia (50%),
constipation (40%), vomiting (34%), neutropenia (30%), insomnia
(27%), headache (26%), decreased appetite (25%), nasopharyngitis
(23%), rash (21%), hypertension (20%), dyspnea (20%),
mucositis/stomatitis (20%), dizziness (18%), back pain (18%),
dyspepsia (18%), leukopenia (17%), cough (16%), urinary tract
infection (13%), anxiety (11%), dry mouth (10%), AST/ALT elevation
(10%), dysgeusia (10%), palpitations (10%).
Common lab abnormalities (Grades 1-4) in ≥25% of patients who
received ZEJULA in NOVA included: decrease in hemoglobin (85%),
decrease in platelet count (72%), decrease in white blood cell
count (66%), decrease in absolute neutrophil count (53%), increase
in AST (36%) and increase in ALT (28%).
Treatment of Advanced HRD+ Ovarian Cancer
Most common adverse reactions (Grades 1-4) in ≥10% of
patients who received ZEJULA in QUADRA were nausea (67%), fatigue
(56%), thrombocytopenia (52%), anemia (51%), vomiting (44%),
constipation (36%), abdominal pain (34%), musculoskeletal pain
(29%), decreased appetite (27%), dyspnea (22%), insomnia (21%),
neutropenia (20%), headache (19%), diarrhea (17%), acute kidney
injury (17%), urinary tract infection (15%), hypertension (14%),
cough (13%), dizziness (11%), AST/ALT elevation (11%), blood
alkaline phosphatase increased (11%).
Common lab abnormalities (Grades 1-4) in ≥25% of patients who
received ZEJULA in QUADRA included: decreased hemoglobin (83%),
increased glucose (66%), decreased platelets (60%), decreased
lymphocytes (57%), decreased leukocytes (53%), decreased magnesium
(46%), increased alkaline phosphatase (40%), increased gamma
glutamyl transferase (40%), increased creatinine (36%), decreased
sodium (34%), decreased neutrophils (34%), increased aspartate
aminotransferase (29%), and decreased albumin (27%).
Please see
accompanying Prescribing
Information
About GSK
GSK is a science-led global healthcare company with a special
purpose: to help people do more, feel better, live longer. For
further information please visit www.gsk.com/about-us.
GSK enquiries:
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Media enquiries:
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Tim
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Media enquiries:
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Analyst/Investor
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Cautionary statement regarding forward-looking
statements
GSK
cautions investors that any forward-looking statements or
projections made by GSK, including those made in this announcement,
are subject to risks and uncertainties that may cause actual
results to differ materially from those projected. Such factors
include, but are not limited to, those described under Item 3.D
"Risk Factors" in the company's Annual Report on Form 20-F for 2019
and any impacts of the COVID-19 pandemic.
Registered in England & Wales:
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3888792
Registered Office:
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Great West Road
Brentford,
Middlesex
TW8
9GS
[i] Konstantinopoulos
PA, Ceccaldi R, Shapiro GI,
D'Andrea AD. Homologous Recombination Deficiency:
Exploiting the Fundamental Vulnerability of Ovarian
Cancer. Cancer
Discov. 2015; 5(11):
1137-54.
[ii] SEER Cancer Stat
Facts: Ovarian Cancer. National Cancer Institute. Bethesda,
MD. http://seer.cancer.gov/statfacts/html/ovary.html.
Accessed October 10, 2018.
[iii] American Cancer Society
"Key Statistics for Ovarian Cancer." https://www.cancer.org/cancer/ovarian-cancer/about/key-statistics.html
[iv] Lorusso D, Mancini
M, Di Rocco R, Fontanelli R, Raspagliesi F. The role of secondary
surgery in recurrent ovarian cancer [published online August 5,
2012]. Int J Surg
Oncol. 2012.
doi:10.1155/2012/613980
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorised.
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GlaxoSmithKline plc
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(Registrant)
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Date: April
30, 2020
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By:/s/ VICTORIA
WHYTE
--------------------------
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Victoria Whyte
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Authorised
Signatory for and on
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behalf
of GlaxoSmithKline plc
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