FORM 6-K
SECURITIES AND EXCHANGE COMMISSION
Washington D.C. 20549
Report of Foreign Issuer
Pursuant to Rule 13a-16 or 15d-16 of
the Securities Exchange Act of 1934
For
period ending
08 March
2019
GlaxoSmithKline plc
(Name
of registrant)
980 Great West Road, Brentford, Middlesex, TW8 9GS
(Address
of principal executive offices)
Indicate
by check mark whether the registrant files or
will
file annual reports under cover Form 20-F or Form 40-F
Form
20-F x Form 40-F
--
Indicate
by check mark whether the registrant by furnishing the
information
contained in this Form is also thereby furnishing the
information
to the Commission pursuant to Rule 12g3-2(b) under the
Securities
Exchange Act of 1934.
Yes
No x
Issued: 7 March 2019, London UK - LSE Announcement
ViiV Healthcare presents positive, 48-week data from two pivotal
phase III studies showing long-acting, injectable two-drug regimen
of cabotegravir and rilpivirine has similar efficacy to daily,
three-drug oral treatment in adults living with HIV-1
infection
Comprehensive data from ATLAS and FLAIR studies presented today at
the 2019 Conference on Retroviruses and Opportunistic Infections
show investigational long-acting injectable to be effective in
maintaining viral suppression
London, 7 March 2019
-
ViiV Healthcare today presented comprehensive 48-week data from the
ATLAS (Antiretroviral Therapy as Long-Acting Suppression) and FLAIR
(First Long-Acting Injectable Regimen) pivotal phase III studies of
the novel, investigational, long-acting regimen of cabotegravir and
rilpivirine. These two studies met their primary endpoints, showing
that the combination of ViiV Healthcare's cabotegravir and
Janssen's rilpivirine, injected every four weeks, was non-inferior
in maintaining viral suppression in adults infected with human
immunodeficiency virus type-1 (HIV-1) when compared to a standard
of care, daily, oral three-drug regimen. These data were presented
today at the 2019 Conference on Retroviruses and Opportunistic
Infections (CROI) in Seattle, Washington.
John C. Pottage, Jr., M.D., Chief Scientific and Medical Officer of
ViiV Healthcare, said:
"With FLAIR and ATLAS, we now have positive
results from two pivotal phase III studies demonstrating that this
long-acting, once-monthly injectable regimen has similar efficacy,
safety and tolerability to a daily oral three-drug regimen for the
treatment of HIV. We are also encouraged by patient
preference data showing that nearly all participants who switched
to the long-acting injectable regimen preferred it over their prior
oral therapy. If approved, this two-drug regimen would give people
living with HIV one month between each dose of antiretroviral
therapy, changing HIV treatment from 365 dosing days per year, to
just 12. We look forward to submitting applications to
regulatory authorities later this year."
ATLAS 48-week efficacy and safety results
The global, pivotal, phase III ATLAS study met its primary
endpoint, with cabotegravir and rilpivirine demonstrating
non-inferiority to an oral three-drug regimen of two nucleoside
reverse transcriptase inhibitors (NRTIs) plus a third agent, as
measured by the proportion of participants with plasma HIV-1 RNA
≥50 copies per millilitre (c/mL) using the FDA Snapshot
algorithm at Week 48 (cabotegravir + rilpivirine: 5/308 [1.6%],
current antiretroviral therapy [CAR]: 3/308 [1.0%], adjusted
difference: 0.6%, 95% confidence interval [CI]: -1.2, 2.5). The
study found virologic suppression rates (HIV-1 RNA <50 c/mL) at
Week 48 were similar between treatment arms (cabotegravir +
rilpivirine: 285/308 [92.5%], CAR: 294/308 [95.5%], adjusted
difference: -3%, 95% CI: -6.7, 0.7).
Confirmed virologic failure (CVF) was infrequent. Three
participants (approximately 1% of the study population) who
received long-acting cabotegravir plus rilpivirine developed CVF
with subsequent identification of resistance mutations to one or
both agents. In two of these cases, pre-existing NNRTI
resistance was identified. Two of the three individuals were from
Russia and all three had HIV-1 A subtypes, which are seen
frequently in Russia, Eastern Europe and East Africa; however, they
are seen infrequently in other parts of the world. This unexpected
pattern warrants further investigation. In the oral CAR arm, there
were four participants who developed CVF, three of whom developed
drug resistance mutations.
Treatment with cabotegravir and rilpivirine was generally
well-tolerated, with low rates of serious adverse events (SAEs)
(13/308 [4.2%]) and adverse event (AE) withdrawals (10/308 [3.2%]).
Of the participants who received cabotegravir and rilpivirine
injections, 83% (250/303) reported an injection site reaction (ISR)
at some point through the 48-week study. A majority of injections
did not result in ISRs being reported, as out of a total of 6978
injections administered during the 48-week study, 1460 ISRs were
reported. Most ISR events (98.5%) were mild or moderate (mild:
1156/1460, moderate: 283/1460) and lasted an average of three days.
Four participants (1.3%) withdrew for injection-related
events.
Patient treatment satisfaction significantly improved after
switching to the long-acting injectable from the previous oral
therapy compared to remaining on oral therapy at Week 44 based on
the HIV Treatment Satisfaction Questionnaire (HIVTSQs mean
difference 5.68; 95% CI [4.37, 6.9]; p<0.001). Patient
preference data from a single-item question administered at Week 48
showed that 266/308 (86.4%) preferred the long-acting injectable
regimen whereas 7/308 (2.3%) preferred their previous oral
therapy.
Susan Swindells, MBBS, Professor, Department of Internal Medicine,
Section of Infectious Diseases at the University of Nebraska
Medical Center and ATLAS principal investigator,
said:
"The positive safety
and efficacy results from the ATLAS study reinforce the potential
of cabotegravir and rilpivirine as the first long-acting,
injectable option for people living with HIV. This novel approach
may help alleviate the burden often associated with daily oral
treatment regimens and contribute to making HIV a smaller part of
peoples' lives."
FLAIR 48-week efficacy and safety results
The global, pivotal, phase III FLAIR study met its primary
endpoint, with cabotegravir and rilpivirine demonstrating
non-inferiority to Triumeq
(abacavir/dolutegravir/lamivudine-ABC/DTG/3TC), as measured by the
proportion of participants with plasma HIV-1 RNA ≥50 c/mL
using the FDA Snapshot algorithm at Week 48 (cabotegravir +
rilpivirine: 6/283 [2.1%], Triumeq 7/283 [2.5%], adjusted
difference: -0.4%, 95% CI: -2.8, 2.1). The study found
virologic suppression rates (HIV-1 RNA <50 c/mL) at Week 48 were
similar between treatment arms (cabotegravir + rilpivirine: 265/283
[93.6%], Triumeq: 264/283 [93.3%], adjusted difference: 0.4%. 95%
CI: -3.7, 4.5).
CVF was infrequent across both treatment arms. Of the individuals
who received long-acting cabotegravir plus rilpivirine, there were
three confirmed virologic failures (approximately 1% of the study
population), all of whom had treatment-emergent, NNRTI and INSTI
resistance. All of these individuals were from Russia and
had HIV-1 subtype A1, which is seen frequently in Russia,
Eastern Europe and East Africa; however, it is seen infrequently in
other parts of the world. This unexpected pattern warrants further
investigation. Three participants in the Triumeq arm developed CVF
with no treatment emergent resistance.
Treatment with cabotegravir and rilpivirine was generally
well-tolerated, with low rates of SAEs (18/283
[6.4%]) and AEs leading to withdrawal (9/283 [3.2%]). Of the
participants who received cabotegravir and rilpivirine injections,
86 percent (239/278) reported an ISR at some point through the
48-week study. A majority of injections did not result in an ISR
being reported, with a total of 7704 injections administered
during the 48-week study resulting in 2203 ISR
events. Nearly all ISRs (99.4%) were mild or moderate
(mild: 1907/2203, moderate: 282/2203), with a median duration of
three days and the frequency of these events decreasing over time.
Four participants (1.4%) withdrew for injection-related
events.
Patient treatment satisfaction significantly improved after
switching to the long-acting injectable from the previous oral
therapy compared to remaining on oral therapy at Week 48 based on
the HIV Treatment Satisfaction Questionnaire (HIVTSQc mean
difference 4.1; 95% CI [2.8, 5.5], p<0.001). Patient preference
data from a single-item question administered at Week 48 showed
that 257/283 (90.8%) preferred the long-acting injectable regimen
whereas 2/283 (0.7%) preferred their previous oral
therapy.
Chloe Orkin, M.D., Consultant Physician and Clinical Professor at
Queen Mary University of London and FLAIR principal investigator,
said:
"The robust results
of the FLAIR study lend further evidence to the potential of
cabotegravir and rilpivirine as an alternative option for people
currently on daily, oral therapy. This long-acting, injectable
two-drug regimen may provide an opportunity to change the paradigm
for people living with HIV by breaking the cycle of a daily pill,
which has been a defining characteristic of HIV therapy for several
decades."
In addition to the once-monthly dosing schedule being evaluated in
the ATLAS study, ViiV Healthcare is investigating the long-acting,
two-drug regimen of cabotegravir and rilpivirine administered every
two months in the ATLAS-2M study. The company plans to use the data
from the FLAIR and ATLAS studies for future regulatory
submissions.
This investigational, long-acting, injectable regimen is being
co-developed as part of a collaboration with Janssen Sciences
Ireland UC and is not approved by regulatory authorities anywhere
in the world.
Notes to editors
About ATLAS (NCT02951052)
The ATLAS study is part of ViiV Healthcare's innovative clinical
trial programme for two-drug regimens. The study includes 616 men
and women living with HIV and is being conducted at research
centres in Argentina, Australia, Canada, France, Germany, Italy,
Mexico, Russia, South Africa, South Korea, Spain, Sweden, and the
United States.
ATLAS is a phase III, open-label, active-controlled, multicentre,
parallel-group, non-inferiority study designed to assess the
antiviral activity and safety of a two-drug regimen of long-acting,
injectable cabotegravir and rilpivirine dosed every four weeks
compared to continuation of current oral anti-retroviral therapy
(ART) of two nucleoside reverse transcriptase inhibitors (NRTIs)
plus an integrase strand transfer inhibitor (INI), non-nucleoside
reverse transcriptase inhibitor (NNRTI), or protease inhibitor (PI)
among virally suppressed individuals. The primary endpoint for
ATLAS is the proportion of participants with plasma HIV-1 RNA
≥50 c/mL per the FDA Snapshot algorithm at Week 48 (Missing,
Switch, or Discontinuation = Failure, Intent-to-Treat Exposed
[ITT-E] population). Subjects were required to be virally
suppressed for six months or greater, on first or second regimen,
with no prior failure.
For further information please see
https://clinicaltrials.gov/ct2/show/NCT02951052
.
About FLAIR (NCT02938520)
FLAIR includes 566 men and women living with HIV and is being
conducted at research centres in Canada, France, Germany,
Italy, Japan, the Netherlands, Russia, South Africa, Spain, the
United Kingdom, and the United States.
FLAIR is a phase III, randomised, open-label, multicentre,
parallel-group, non-inferiority study designed to assess the
antiviral activity and safety of a two-drug regimen of
intramuscular, long-acting, injectable cabotegravir and rilpivirine
in virologically suppressed adults living with HIV, following 20
weeks of induction therapy with Triumeq. The primary endpoint for
FLAIR is the proportion of participants with plasma HIV-1 RNA
≥50 c/mL per the FDA Snapshot algorithm at Week
48 (Missing, Switch, or Discontinuation = Failure,
Intent-to-Treat Exposed [ITT-E] population).
For further information please see
https://clinicaltrials.gov/ct2/show/NCT02938520
.
About cabotegravir
Cabotegravir is an investigational integrase inhibitor (INI) and is
not approved by regulatory authorities anywhere in the world.
Cabotegravir is being developed by ViiV Healthcare for the
treatment and prevention of HIV. It is being evaluated as a
long-acting formulation for intramuscular injection and also as a
once-daily oral tablet for use as a lead-in, to establish the
tolerability of cabotegravir prior to long-acting
injection.
About rilpivirine
EDURANT® (rilpivirine) is a once daily non-nucleoside reverse
transcriptase inhibitor (NNRTI) used for the treatment of human
immunodeficiency virus (HIV-1) infection in combination with other
antiretroviral agents in antiretroviral treatment-naïve adult
patients with a viral load ≤ 100,000 HIV RNA copies/mL.
Long-acting injectable rilpivirine is not approved by regulatory
authorities anywhere in the world.
Rilpivirine was developed by Janssen Sciences Ireland UC, one of
the Janssen Pharmaceutical Companies of Johnson & Johnson.
Rilpivirine is approved in the U.S. and E.U. as EDURANT® as a
25mg tablet taken once-a-day and is always taken with a meal. The
most common side effects of EDURANT include: depression, headache,
trouble sleeping (insomnia) and rash.
Important Safety Information
(ISI) for EDURANT
®
(Rilpivirine
Note: this is taken from the US label and local variations apply.
Please refer to applicable local labelling.
Professional Indication(s) and Important Safety
Information
INDICATIONS AND USAGE
EDURANT
®
(rilpivirine),
in combination with other antiretroviral agents, is a
non-nucleoside reverse transcriptase inhibitor (NNRTI) indicated
for the treatment of human immunodeficiency virus type 1 (HIV-1)
infection in antiretroviral treatment-naïve patients 12 years
of age and older and weighing at least 35 kg with HIV-1 RNA less
than or equal to 100,000 copies/mL at the start of
therapy.
The following points should be considered when initiating therapy
with EDURANT
®
:
●
More EDURANT
®
-treated
subjects with HIV-1 RNA greater than 100,000 copies/mL at the start
of therapy experienced virologic failure (HIV-1 RNA ≥50
copies/mL) compared to EDURANT
®
-treated
subjects with HIV-1 RNA less than or equal to 100,000
copies/mL
EDURANT
®
is
not recommended for patients less than 12 years of
age.
CONTRAINDICATIONS
●
Coadministration of EDURANT
®
with
the following drugs is contraindicated because significant
decreases in rilpivirine plasma concentrations may occur due to
CYP3A enzyme induction or gastric pH increase, which may result in
loss of virologic response and possible resistance and
cross-resistance: carbamazepine, oxcarbazepine, phenobarbital,
phenytoin, rifampin, rifapentine, proton pump inhibitors such as
esomeprazole, lansoprazole, omeprazole, pantoprazole, and
rabeprazole, systemic dexamethasone (more than single dose), and
products containing St. John's wort
(Hypericum
perforatum)
Warnings and Precautions
●
Skin and Hypersensitivity
Reactions:
Severe skin and
hypersensitivity reactions have been reported during the
postmarketing experience, including cases of Drug Reaction with
Eosinophilia and Systemic Symptoms (DRESS), with
rilpivirine-containing regimens. While some skin reactions were
accompanied by constitutional symptoms such as fever, other skin
reactions were associated with organ dysfunctions, including
elevations in hepatic serum biochemistries.
EDURANT
®
should
be discontinued immediately if signs or symptoms of severe skin or
hypersensitivity reactions develop, including but not limited to,
severe rash or rash accompanied by fever, blisters, mucosal
involvement, conjunctivitis, facial edema, angioedema, hepatitis or
eosinophilia. Clinical status including laboratory parameters
should be monitored and appropriate therapy should be
initiated
●
Hepatotoxicity:
Hepatic
adverse events were reported. Patients with underlying hepatic
disease, including hepatitis B or C, or marked elevations in
transaminases before treatment may be at increased risk for
worsening or development of transaminase elevations. Monitor liver
function tests (LFTs) before and during treatment. A few
hepatotoxicity cases occurred in patients with no pre-existing
hepatic disease or other identifiable risk factors; therefore,
monitoring of LFTs should be considered in all
patients
●
Depressive
Disorders:
Severe
depressive disorders, defined as depressed mood, depression,
dysphoria, major depression, mood altered, negative thoughts,
suicide attempt, and suicidal ideation, have been reported with
EDURANT
®
.
Immediate medical evaluation is recommended for severe depressive
symptoms
●
Fat
Redistribution:
Redistribution and/or accumulation of body fat
have been observed in patients receiving ARV therapy. The causal
relationship, mechanism, and long-term consequences of these events
have not been established
●
Immune Reconstitution
Syndrome
has been reported
in patients treated with combination ARV therapy, including
EDURANT
®
.
Autoimmune disorders (such as Graves disease, polymyositis, and
Guillain-Barré syndrome) have also been reported to occur in
the setting of immune reconstitution; however, the time to onset is
more variable and can occur many months after initiation of
treatment
Drug Interactions
●
EDURANT
®
should
be used with caution when coadministered with drugs that may reduce
the exposure of rilpivirine, such as antacids and
H
2
-receptor
antagonists
●
Concomitant use of EDURANT
®
with
rifabutin may cause a decrease in the plasma concentrations of
rilpivirine. Please read the Dosage and Administration Section of
the Prescribing Information for more details regarding the
concomitant use of EDURANT
®
and
rifabutin
●
EDURANT
®
should
be used with caution when coadministered with a drug with a known
risk of Torsade de Pointes
●
EDURANT
®
should
not be used in combination with NNRTIs
This is not a complete list of potential drug
interactions.
Please see
full
Prescribing
Information
for more
details.
Use in Specific Populations
●
Hepatic
Impairment:
EDURANT
®
should
be used with caution in patients with severe hepatic impairment
(Child-Pugh Class C) as pharmacokinetics of
EDURANT
®
have
not been evaluated in these patients
●
Pregnancy:
In a clinical trial, total rilpivirine
exposures were generally lower during pregnancy compared to the
postpartum period
●
Lactation:
Women infected with HIV should be instructed
not to breastfeed due to the potential for HIV
transmission
This list of uses in specific populations is not
complete.
Please refer to the
EDURANT
®
Prescribing
Information
for additional
information.
Adverse Reactions
●
The most common adverse drug reactions reported
(incidence >2%) of at least moderate intensity (≥ Grade 2)
in patients taking EDURANT
®
through
96 weeks were depressive disorders (5%), headache (3%), insomnia
(3%), and rash (3%)
This is not a complete list of all
adverse drug reactions reported with the use of
EDURANT
®
.
Please refer to the
full
Prescribing
Information
for a complete
list of adverse drug reactions.
Full US prescribing information including is available
at:
http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/EDURANT-pi.pdf
For the EU Summary of Product Characteristics, please
visit:
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002264/WC500118874.pdf
About ViiV Healthcare
ViiV Healthcare is a global specialist HIV company established in
November 2009 by GlaxoSmithKline (LSE: GSK) and Pfizer (NYSE: PFE)
dedicated to delivering advances in treatment and care for people
living with HIV and for people who are at risk of becoming infected
with HIV. Shionogi joined as a shareholder in October 2012. The
company's aim is to take a deeper and broader interest in HIV/AIDS
than any company has done before and take a new approach to deliver
effective and innovative medicines for HIV treatment and
prevention, as well as support communities affected by
HIV.
For more information on the company, its management, portfolio,
pipeline, and commitment, please visit
www.viivhealthcare.com
.
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 2017.
About GSK
GSK - one of the world's leading research-based pharmaceutical and
healthcare companies - is committed to improving the quality of
human life by enabling people to do more, feel better and live
longer. For further information please
visit
www.gsk.com
.
|
ViiV
Healthcare Media enquiries:
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Melinda
Stubbee
|
+1 919
491 0831
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Audrey
Abernathy
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+1 919
605 4521
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GSK
Global Media enquiries:
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Simon
Steel
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+44 (0)
20 8047 5502
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Analyst/Investor
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Spencer
Sarah
Elton-Farr
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751 7002
+44 (0)
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Danielle
Smith
James
Dodwell
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+44 (0)
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+44 (0)
20 8047 2406
|
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Jeff
McLaughlin
|
+1 215
751 7002
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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.
|
|
GlaxoSmithKline plc
|
|
|
(Registrant)
|
|
|
|
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Date: March
08, 2019
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By: 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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