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 September, 2019
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 . . . . . . . .
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(1): ____
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(7): ____
Issued: 28 September 2019, London UK
Phase 3 PRIMA trial
of Zejula® (niraparib)
is the first study to show a PARP inhibitor significantly
improves PFS, regardless of biomarker status, when given as
monotherapy in women with first-line platinum responsive advanced
ovarian cancer
● The PRIMA study, presented in a Presidential
Symposium at the 2019 European Society for Medical Oncology
congress and simultaneously published in The New England Journal of
Medicine, demonstrates
that niraparib treatment resulted in a 38% reduction in the risk of
disease progression or death in the overall study population when
compared to placebo
● Importantly women in both the HR-deficient ('HRD
positive') and HR-proficient ('HRD negative') subgroups experienced
a clinically meaningful and statistically significant
benefit
GlaxoSmithKline plc (LSE/NYSE: GSK) today announced results
from PRIMA (ENGOT-OV26/GOG-3012), the Phase 3 randomised,
double-blind, placebo-controlled study of Zejula (niraparib) as a
maintenance therapy in women with first-line ovarian cancer
following a response to platinum-based chemotherapy. Niraparib
treatment resulted in a 38% reduction in the risk of disease
progression or death in the overall population (PFS, HR 0.62; 95%
CI, 0.50-0.75; p<0.001).
These results were driven by a clinically meaningful reduction in
risk of progression in women with:
●
BRCA mutation tumours
(risk reduction of 60%, HR 0.40 (95% CI, 0.27-0.62)
p<0.001).
●
HR-deficient BRCA wild
type tumours (risk reduction of 50%, HR 0.50 (95% CI, 0.30-0.83),
p=0.006).
●
HR-proficient tumours
(risk reduction of 32%, HR 0.68 (95% CI, 0.49-0.94),
p=0.020).
The PRIMA study enrolled patients with a response to their
first-line treatment with platinum-based chemotherapy including
those with high risk of disease progression, a population with high
unmet need and previously under-represented in first-line
ovarian cancer studies.
Dr. Hal Barron, Chief Scientific Officer and President R&D, GSK
said: "Ovarian cancer is the eighth most commonly occurring cancer
in women worldwide and women with this devastating disease have a
five-year survival rate of less than 50%. PRIMA is a landmark study
as we believe these data have the potential to fundamentally change
how women with ovarian cancer are treated."
In an interim analysis of overall survival (OS), niraparib also
demonstrated an encouraging trend toward improvement in OS relative
to placebo. A pre-planned interim analysis of OS numerically
favoured niraparib in the overall population (HR 0.70; 95% CI
0.44-1.11). In the HR-deficient subgroup, 91% of women on niraparib
were alive at 24 months vs. 85% for placebo (HR=0.61; 95% CI,
0.27-1.40). These data are not yet mature, and the significance is
not fully known. The OS interim analysis also showed 81% of women
receiving niraparib in the HR-proficient subgroup were alive at 24
months vs. 59% of women receiving placebo (HR=0.51; 95% CI,
0.27-0.97).
Dr. Antonio Gonzalez, co-director, department of medical oncology,
Clinica Universidad de Navarra, and Primary Investigator for PRIMA
said: "The PRIMA study demonstrated the importance of maintenance
therapy and the benefit that niraparib provided to women with
ovarian cancer. I believe that niraparib monotherapy after surgery
and platinum-based chemotherapy could be an important new treatment
option for patients."
Niraparib is not currently approved in the first-line ovarian
cancer maintenance setting. GSK will share these data with the
relevant health authorities and is on track to file by the end of
the year.
The safety profile demonstrated in PRIMA did not differ from the
established safety profile. The most common grade 3 or higher
adverse events with niraparib included anaemia (31%),
thrombocytopenia (29%), and neutropenia (13%). Implementation of an
individualised dosing regimen based on body weight and/or platelet
count reduced the incidence of haematological treatment-emergent
adverse events. No new safety signals were identified. Validated
patient reported outcomes indicate quality of life was similar
between the niraparib and placebo treatment arms.
Niraparib is marketed in the United States and Europe under the
trade name Zejula®.
####
About PRIMA
PRIMA is a double-blind, randomised Phase 3 study designed to
evaluate niraparib versus placebo in first-line Stage III or IV
ovarian cancer patients. The study assessed the efficacy of
niraparib as maintenance treatment, as measured by progression free
survival. Patients with a response to first-line platinum
chemotherapy were randomised 2:1 to niraparib or placebo. The trial
was amended to include an individualised niraparib starting dose of
200 mg once-daily in patients with baseline weight <77kg and/or
platelet count <150K/lL and 300 mg in all other
patients.
About Zejula (niraparib)
Niraparib is indicated as monotherapy for the maintenance treatment
of adult patients with
platinum-sensitive relapsed high grade serous epithelial ovarian,
fallopian tube, or primary peritoneal
cancer who are in response (complete or partial) to platinum-based
chemotherapy.
Niraparib is an oral, once-daily PARP inhibitor that is currently
being evaluated in three pivotal trials. GSK is building a robust
niraparib franchise 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 a Phase 3 trial as first-line monotherapy
maintenance treatment in patients with first-line ovarian cancer
(the PRIMA trial), a Phase 3 study as a first-line triplet
maintenance treatment in ovarian cancer (FIRST), a Phase 3 trial
for the treatment of patients with
germline BRCA-mutated,
metastatic breast cancer (the BRAVO trial), and a Phase 2 study of
niraparib combined with bevacizumab maintenance treatment in
advanced ovarian cancer (OVARIO).
Several combination studies are also underway, including trials of
niraparib plus pembrolizumab in metastatic, triple-negative breast
cancer and advanced, platinum-resistant ovarian cancer (the TOPACIO
trial). Janssen Biotech has licensed rights to develop and
commercialise niraparib specifically for patients with prostate
cancer worldwide, except in Japan.
Important Safety Information for ZEJULA
Myelodysplastic Syndrome/Acute Myeloid Leukaemia (MDS/AML),
including some fatal cases, was reported in 1.4% of patients
receiving ZEJULA vs 1.1% of patients receiving placebo in Trial 1
(NOVA), and 0.9% of patients treated with ZEJULA in all clinical
studies. The duration of ZEJULA treatment in patients prior to
developing MDS/AML varied from <1 month to 2 years. All patients
had received prior chemotherapy with platinum and some had also
received other DNA damaging agents and radiotherapy. Discontinue
ZEJULA if MDS/AML is confirmed.
Haematologic adverse reactions (thrombocytopenia, anaemia and
neutropenia) have been reported in patients receiving ZEJULA. Grade
≥3 thrombocytopenia, anaemia and neutropenia were reported in
29%, 25%, and 20% of patients receiving ZEJULA, respectively.
Discontinuation due to thrombocytopenia, anaemia, and neutropenia
occurred, in 3%, 1%, and 2% of patients, respectively. Do not start
ZEJULA until patients have recovered from haematological toxicity
caused by prior chemotherapy (≤ Grade 1). Monitor complete
blood counts weekly for the first month, monthly for the next 11
months of treatment, and periodically thereafter. If haematological
toxicities do not resolve within 28 days following interruption,
discontinue ZEJULA, and refer the patient to a haematologist for
further investigations.
Hypertension and hypertensive crisis have been reported in patients
receiving ZEJULA. Grade 3-4 hypertension occurred in 9% of patients
receiving ZEJULA vs 2% of patients receiving placebo in Trial 1,
with discontinuation occurring in <1% of patients. Monitor blood
pressure and heart rate monthly for the first year and periodically
thereafter during treatment with ZEJULA. 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.
Based on its mechanism of action, ZEJULA can cause foetal harm.
Advise females of reproductive potential of the potential risk to a
foetus and to use effective contraception during treatment and for
6 months after receiving their final dose. 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.
In clinical studies, the most common adverse reactions (Grades 1-4)
in ≥10% of patients included: thrombocytopenia (61%), anaemia
(50%), neutropenia (30%), leukopenia (17%), palpitations (10%),
nausea (74%), constipation (40%), vomiting (34%), abdominal
pain/distention (33%), mucositis/stomatitis (20%), diarrhoea (20%),
dyspepsia (18%), dry mouth (10%), fatigue/asthenia (57%), decreased
appetite (25%), urinary tract infection (13%), aspartate
aminotransferase (AST)/alanine aminotransferase (ALT) elevation
(10%), myalgia (19%), back pain (18%), arthralgia (13%), headache
(26%), dizziness (18%), dysgeusia (10%), insomnia (27%), anxiety
(11%), nasopharyngitis (23%), dyspnoea (20%), cough (16%), rash
(21%) and hypertension (20%).
Common lab abnormalities (Grades 1-4) in ≥25% of patients
included: decrease in haemoglobin (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%).
About Ovarian Cancer
Approximately 300,000 women are diagnosed with ovarian cancer each
year. Ovarian cancer is the eighth most frequent cause of cancer
death among women. Despite high response rates to platinum-based
chemotherapy in the second-line advanced treatment setting,
approximately 85% of patients will experience recurrence within two
years. Late-line treatment options for patients with ovarian cancer
are few, with the proportion of patients achieving an overall
response typically less than 10% when treated with
chemotherapy.
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 cells, either alone or in
combination.
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.
GSK enquiries:
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UK
Media enquiries:
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Simon
Steel
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+44 (0)
20 8047 5502
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(London)
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Tim
Foley
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+44 (0)
20 8047 5502
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(London)
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US
Media enquiries:
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Kristen
Neese
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+1
(804) 217-8147
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(Philadelphia)
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Analyst/Investor
enquiries:
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Sarah
Elton-Farr
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+44 (0)
20 8047 5194
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(London)
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Danielle
Smith
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+44 (0)
20 8047 2406
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(London)
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James
Dodwell
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+44 (0)
20 8047 2406
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(London)
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Jeff
McLaughlin
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+1 215
751 7002
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(Philadelphia)
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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
'Principal risks and uncertainties' in the company's Annual Report
on Form 20-F for 2018.
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Registered in England & Wales:
No.
3888792
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Registered Office:
980
Great West Road
Brentford,
Middlesex
TW8
9GS
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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: September 30, 2019
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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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