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 August 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 . . . . . . . .
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): ____
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Issued: 6 August 2020, London UK
FDA approves GSK's BLENREP (belantamab mafodotin-blmf) for the
treatment of patients with relapsed or refractory multiple
myeloma
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BLENREP
is a first-in-class anti-BCMA (B-cell maturation antigen) therapy
for patients whose disease has progressed despite prior
treatment with an immunomodulatory agent, proteasome
inhibitor and anti-CD38 antibody
●
BLENREP
is the fifth major medicine approval for GSK in 2020
GlaxoSmithKline plc (LSE/NYSE: GSK) announced the US Food and Drug
Administration (FDA) has approved BLENREP (belantamab
mafodotin-blmf) as a monotherapy treatment for adult patients with
relapsed or refractory multiple myeloma who have received at least
four prior therapies including an anti-CD38 monoclonal antibody, a
proteasome inhibitor and an immunomodulatory agent. This
indication is approved under accelerated approval based on response
rate. Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory
trials. BLENREP is the first anti-BCMA (B-cell maturation
antigen) therapy approved anywhere in the world.[i]
Dr Hal Barron, Chief Scientific Officer and President R&D, GSK,
said: "As the second most common form of blood cancer in the US,
multiple myeloma is an incurable and devastating disease. BLENREP
is the first approved anti-BCMA therapy and has the potential to
transform the treatment of patients with relapsed or refractory
myeloma who have limited treatment options today.''
BLENREP is GSK's fifth major medicine approval in 2020 across areas
of significant unmet medical need such as cancer, HIV and chronic
kidney disease. This approval marks the second FDA approval for
GSK's oncology portfolio in four months.
BLENREP employs a multi-faceted mechanism of action and is directed
toward BCMA, a cell-surface protein that plays an important role in
the survival of plasma cells and is expressed on multiple myeloma
cells.[ii] The
approval of BLENREP was based on six-month primary results from the
pivotal DREAMM-2 study, which enrolled patients with relapsed or
refractory multiple myeloma who had actively progressing disease
that had worsened despite current standard of care.
Dr Sagar Lonial, MD, Chief Medical Officer, Winship Cancer
Institute of Emory University in Atlanta, Georgia, Chair of Emory
Department of Hematology and Medical Oncology and Principal
Investigator for DREAMM-2, said: "While treatable, refractory
multiple myeloma is a significant clinical challenge with poor
outcomes for patients whose disease has become resistant to the
current standard of care. Due to the limited options currently
available, these patients are often retreated with drugs from the
same classes after they relapse, which is why the approval of
BLENREP, the first anti-BCMA therapy, is significant for both
patients and physicians alike."
In the DREAMM-2 study, treatment with single-agent BLENREP 2.5
mg/kg every three weeks demonstrated a clinically meaningful
overall response rate (ORR) of 31% (97.5% CI; 21-43) in patients
who had received a median of seven prior lines of treatment (n=97).
The median duration of response (DoR) had not been reached at the
six-month analysis, but 73% of responders had a DoR equal to or
greater than six months. The most commonly reported adverse events
(≥20%) were keratopathy, decreased visual acuity, nausea,
blurred vision, pyrexia, infusion-related reactions, and fatigue.
Keratopathy is characterised as changes in the corneal epithelium
as seen on eye examination, which can manifest with or without
symptoms.
Ocular adverse reactions occurred in 77% of the 218 patients
in the pooled safety population and included keratopathy (76%),
changes in visual acuity (55%), blurred vision (27%) and dry eye
(19%). Corneal adverse events were monitored with eye exams prior
to each dose, allowing for dose reductions or interruptions as
appropriate. Patients also used preservative-free eye
drops. Keratopathy leading to treatment discontinuation
affected 2.1% of patients in the 2.5 mg/kg
cohort.[iii]
BLENREP is available through participation in the BLENREP Risk
Evaluation and Mitigation Strategy (REMS), which was developed to
ensure appropriate use of the medicine. The programme requires
education for all physicians prescribing BLENREP and their patients
regarding the ocular risks associated with treatment as well as
monitoring. Additional information about the BLENREP REMS can be
found at www.blenreprems.com or
1-855-209-9188.
Paul Giusti, President and CEO of the Multiple Myeloma Research
Foundation (MMRF), said: "The approval of BLENREP is an important
advancement for patients with relapsed or refractory multiple
myeloma, as it brings a much-needed new treatment to patients who
face limited options due to their progressing disease. We are
grateful for GSK's continued commitment to myeloma patients and
their families."
In 2017, BLENREP was granted Breakthrough Therapy designation by
the FDA, which is intended to facilitate the development of
investigational medicines that have shown clinical promise for
conditions where there is significant unmet need.
About multiple myeloma
Multiple myeloma is the second most common blood cancer in the
US and is generally considered treatable, but not
curable.[iv] In
the US, more than 32,000 people are estimated to be diagnosed with
multiple myeloma this year and nearly 13,000 people will die from
the disease.[v] Research
into new therapies is needed as multiple myeloma commonly becomes
refractory to available treatments.[vi]
About B-cell maturation antigen (BCMA)
The normal function of BCMA is to promote plasma cell survival by
transduction of signals from two known ligands, BAFF (B-cell
activating factor) and APRIL (a proliferation-inducing ligand).
This pathway has been shown to be important for myeloma cell growth
and survival. BCMA expression is limited to B cells at later stages
of development. BCMA is expressed at varying levels in myeloma
patients and BCMA membrane expression is universally detected in
myeloma cell lines.ii
About BLENREP (belantamab
mafodotin-blmf)
BLENREP is an antibody drug conjugate comprising a humanised
anti-B cell maturation antigen (BCMA) monoclonal antibody
conjugated to the cytotoxic agent auristatin F via non-cleavable
linker. The drug linker technology is licensed from Seattle
Genetics; monoclonal antibody is produced using POTELLIGENT
Technology licensed from BioWa.
IMPORTANT SAFETY INFORMATION FOR BLENREP
WARNING: OCULAR TOXICITY
BLENREP caused changes in the corneal epithelium resulting in
changes in vision, including severe vision loss and corneal ulcer,
and symptoms such as blurred vision and dry
eyes.
Conduct ophthalmic exams at baseline, prior to each dose, and
promptly for worsening symptoms. Withhold BLENREP until improvement
and resume, or permanently discontinue, based on
severity.
Because of the risk of ocular toxicity, BLENREP is available only
through a restricted program under a Risk Evaluation and Mitigation
Strategy (REMS) called the BLENREP REMS.
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WARNINGS AND PRECAUTIONS
Ocular Toxicity: Ocular
adverse reactions occurred in 77% of the 218 patients in the pooled
safety population. Ocular adverse reactions included
keratopathy (76%), changes in visual acuity (55%), blurred
vision (27%), and dry eye (19%). Among patients with
keratopathy (n = 165), 49% had ocular symptoms, 65% had
clinically relevant visual acuity changes (decline of 2 or more
lines on Snellen Visual Acuity in any eye), and 34% had both
ocular symptoms and visual acuity changes.
Keratopathy: Keratopathy was
reported as Grade 1 in 7% of patients, Grade 2 in 22%, Grade 3 in
45%, and Grade 4 in 0.5% per the KVA scale. Cases of corneal
ulcer (ulcerative and infective keratitis) have been
reported. Most keratopathy events developed within the first 2
treatment cycles (cumulative incidence of 65% by Cycle 2). Of the
patients with Grade 2 to 4 keratopathy (n = 149), 39% recovered to
Grade 1 or lower after
median follow-up of 6.2 months. Of the 61% who had ongoing
keratopathy, 28% were still on treatment, 9% were in follow-up, and
in 24% the follow-up ended due to death, study withdrawal, or lost
to follow-up. For patients in whom events resolved, the median time
to resolution was 2 months (range: 11 days to 8.3
months).
Visual Acuity Changes: A
clinically significant decrease in visual acuity of worse than
20/40 in the better-seeing eye was observed in 19% of the 218
patients and of 20/200 or worse in the better-seeing eye in 1.4%.
Of the patients with decreased visual acuity of worse than 20/40,
88% resolved and the median time to resolution was 22 days (range:
7 days to 4.2 months). Of the patients with decreased visual acuity
of 20/200 or worse, all resolved and the median duration was 22
days (range: 15 to 22 days).
Monitoring and Patient Instruction: Conduct ophthalmic examinations (visual acuity
and slit lamp) at baseline, prior to each dose, and promptly
for worsening symptoms. Perform baseline examinations
within 3 weeks prior to the first dose. Perform each follow-up
examination at least 1 week after the previous dose and within
2 weeks prior to the next dose. Withhold BLENREP until
improvement and resume at same or reduced dose, or
consider permanently discontinuing based on severity. Advise
patients to use preservative-free lubricant eye drops at
least 4 times a day starting with the first infusion and continuing
until end of treatment. Avoid use of contact lenses unless
directed by an ophthalmologist. Changes in visual acuity may
be associated with difficulty for driving and reading. Advise
patients to use caution when driving or operating
machinery. BLENREP is only available through a restricted
program under a REMS.
BLENREP REMS: BLENREP is
available only through a restricted program under a REMS called the
BLENREP REMS because of the risks of ocular toxicity. Notable
requirements of the BLENREP REMS include the
following:
●
Prescribers
must be certified with the program by enrolling and completing
training in the BLENREP REMS.
●
Prescribers
must counsel patients receiving BLENREP about the risk of ocular
toxicity and the need for ophthalmic examinations prior to each
dose.
●
Patients
must be enrolled in the BLENREP REMS and comply with
monitoring.
●
Healthcare
facilities must be certified with the program and verify that
patients are authorized to receive BLENREP.
●
Wholesalers
and distributers must only distribute BLENREP to certified
healthcare facilities.
Further information is available at www.BLENREPREMS.com and
1-855-209-9188.
Thrombocytopenia: Thrombocytopenia occurred in 69% of 218 patients
in the pooled safety population, including Grade 2 in 13%, Grade 3
in 10%, and Grade 4 in 17%. The median time to onset of the
first thrombocytopenic event was 26.5 days. Thrombocytopenia
resulted in dose reduction, dose interruption, or discontinuation
in 9%, 2.8%, and 0.5% of patients, respectively. Grade 3 to 4
bleeding events occurred in 6% of patients, including Grade 4 in 1
patient. Fatal adverse reactions included cerebral hemorrhage
in 2 patients. Perform complete blood cell counts at baseline and
during treatment as clinically indicated. Consider withholding
and/or reducing the dose based on severity.
Infusion-Related Reactions: Infusion-related reactions occurred in 18% of 218
patients in the pooled safety population, including Grade 3 in
1.8%. Monitor patients for infusion-related
reactions. For Grade 2 or 3 reactions, interrupt the infusion and
provide supportive treatment. Once symptoms resolve, resume at a
lower infusion rate. Administer premedication for all subsequent
infusions. Discontinue BLENREP for life-threatening
infusion-related reactions and provide appropriate emergency
care.
Embryo-Fetal Toxicity: Based on its mechanism of action, BLENREP can
cause fetal harm when administered to a pregnant woman because it
contains a genotoxic compound (the microtubule inhibitor,
monomethyl auristatin F [MMAF]) and it targets actively dividing
cells. Advise pregnant women of the potential risk to a fetus.
Advise females of reproductive potential to use effective
contraception during treatment with BLENREP and for 4 months after
the last dose. Advise males with female partners of reproductive
potential to use effective contraception during treatment with
BLENREP and for 6 months after the last dose.
ADVERSE REACTIONS
The pooled safety population described in Warnings and
Precautions reflects
exposure to BLENREP at a dosage of 2.5 mg/kg or 3.4 mg/kg (1.4
times the recommended dose) administered intravenously once every 3
weeks in 218 patients in DREAMM-2. Of these patients, 194 received
a liquid formulation (not the approved dosage form) rather than the
lyophilized powder. Among the 218 patients, 24% were exposed for 6
months or longer.
The safety of BLENREP as a single agent was evaluated in DREAMM-2.
Patients received BLENREP at the recommended dosage of 2.5 mg/kg
administered intravenously once every 3 weeks (n = 95).
Among these patients, 22% were exposed for 6 months or
longer.
Serious adverse reactions occurred in 40% of patients who received
BLENREP. Serious adverse reactions in >3% of patients included
pneumonia (7%), pyrexia (6%), renal impairment (4.2%), sepsis
(4.2%), hypercalcemia (4.2%), and infusion-related reactions
(3.2%). Fatal adverse reactions occurred in 3.2% of patients,
including sepsis (1%), cardiac arrest (1%), and lung infection
(1%).
Permanent discontinuation due to an adverse reaction occurred in 8%
of patients who received BLENREP; keratopathy (2.1%) was the most
frequent adverse reaction resulting in permanent
discontinuation.
Dosage interruptions due to an adverse reaction occurred in 54% of
patients who received BLENREP. Adverse reactions which required a
dosage interruption in >3% of patients included keratopathy
(47%), blurred vision (5%), dry eye (3.2%), and pneumonia
(3.2%).
Dose reductions due to an adverse reaction occurred in 29% of
patients. Adverse reactions which required a dose reduction in
>3% of patients included keratopathy (23%) and thrombocytopenia
(5%).
The most common adverse reactions (≥20%) were
keratopathy (71%), decreased visual acuity (53%), nausea (24%),
blurred vision (22%), pyrexia (22%), infusion-related reactions
(21%), and fatigue (20%). The most common Grade 3 or 4 (≥5%)
laboratory abnormalities were lymphocytes decreased (22%),
platelets decreased (21%), hemoglobin decreased (18%), neutrophils
decreased (9%), creatinine increased (5%), and gamma-glutamyl
transferase increased (5%).
USE IN SPECIFIC POPULATIONS
Lactation: There is no
data on the presence of belantamab mafodotin-blmf in human milk or
the effects on the breastfed child or milk production. Because of
the potential for serious adverse reactions in the breastfed child,
advise women not to breastfeed during treatment with BLENREP and
for 3 months after the last dose.
Females and Males of Reproductive
Potential: BLENREP can
cause fetal harm when administered to pregnant women. There are no
available data on the use of BLENREP in pregnant women to evaluate
for drug-associated risk. No animal reproduction studies were
conducted with BLENREP.
Pregnancy Testing: Pregnancy
testing is recommended for females of reproductive potential prior
to initiating BLENREP.
Infertility: Based on findings
in animal studies, BLENREP may impair fertility in females and
males. The effects were not reversible in male rats but were
reversible in female rats.
Geriatric Use: Of the 218
patients who received BLENREP in DREAMM-2, 43% were aged 65 to less
than 75 years and 17% were aged 75 years and older. Keratopathy
occurred in 80% of patients aged less than 65 years and 73% of
patients aged 65 years and older. Among the patients who received
BLENREP at the 2.5-mg/kg dose in DREAMM-2 (n = 95), keratopathy
occurred in 67% of patients aged less than 65 years and 73% of
patients aged 65 years and older.
Renal Impairment: No dose
adjustment is recommended for patients with mild or moderate renal
impairment (estimated glomerular filtration rate [eGFR] 30 to
89 mL/min/1.73m2 as
estimated by the Modification of Diet in Renal Disease [MDRD]
equation). The recommended dosage has not been established in
patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73
m2)
or end-stage renal disease (ESRD) with eGFR <15 mL/min/1.73
m2 not
on dialysis or requiring dialysis.
Hepatic Impairment: No
dose adjustment is recommended for patients with mild hepatic
impairment (total bilirubin ≤upper limit of normal [ULN] and
aspartate aminotransferase (AST) >ULN or total bilirubin 1 to
≤1.5 × ULN and any AST). The recommended dosage of
BLENREP has not been established in patients with moderate or
severe hepatic impairment (total bilirubin >1.5 × ULN and
any AST).
INDICATION
BLENREP is indicated for the treatment of adults with relapsed or
refractory multiple myeloma who have received at least 4 prior
therapies, including an anti-CD38 monoclonal antibody, a proteasome
inhibitor, and an immunomodulatory agent.
This indication is approved under accelerated approval based on
response rate. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in
a confirmatory trial(s).
The full Prescribing Information,
including BOXED WARNING and Medication Guide, will be
available here.
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/about-us.
Editor's Note: In addition
to the FDA's approval of BLENREP, GSK has received four major
medicine approvals to date in 2020 for CABENUVA (cabotegravir and
rilpivirine) in Canada, DUVROQ (daprodustat) in Japan and ZEJULA
(niraparib) and RUKOBIA (fostemsavir) in the
US.
GSK enquiries:
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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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Kristen
Neese
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+1 804
217 8147
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(Philadelphia)
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Kathleen
Quinn
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+1 202
603 5003
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(Washington
DC)
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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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Sonya
Ghobrial
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+44 (0)
7392 784784
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(Consumer)
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Danielle
Smith
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+44 (0)
20 8047 0932
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(London)
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James
Dodwell
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+44 (0)
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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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Frannie
DeFranco
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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
"Risk Factors" in the company's Annual Report on Form 20-F for 2019
and as set out in GSK's "Principal risks and uncertainties" section
of the Q2 Results and any impacts of the COVID-19
pandemic.
Registered in England & Wales:
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References
[i] NCI Drug Dictionary -
Anti-BCMA Antibody-Drug Conjugate GSK2857916. National Cancer
Institute.
https://www.cancer.gov/publications/dictionaries/cancer-drug/def/anti-bcma-antibody-drug-conjugate-gsk2857916.
Accessed May 2020.
[ii] Trudel S, Lendvai N,
Popat R, et al. Antibody-drug conjugate, GSK2857916, in
relapsed/refractory multiple myeloma: an update on safety and
efficacy from dose expansion phase I study. Blood Cancer Journal.
2019;9(4).
doi:10.1038/s41408-019-0196-6.
[iii] Lonial, S, et al.
Belantamab mafodotin for relapsed or refractory multiple myeloma
(DREAMM-2): a two-arm, randomised, open-label, phase 2 study.
Lancet Oncol. 2020; 21(2):207-21.
[iv] Estimated number of
incident cases worldwide, both sexes, all ages. World Health
Organization. https://gco.iarc.fr/ Published 2020. Accessed May
2020.
[v] SEER
Cancer Facts & Figures 2019. Available
at: https://seer.cancer.gov/statfacts/html/mulmy.html.
Accessed December 19, 2019.
[vi] Nooka AK, Kastritis
E, Dimopoulos MA. Treatment options for relapsed and refractory
multiple myeloma. Blood. 2015;125(20)
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: August
06, 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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