Blueprint
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 February
2018
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
8 February, 2018, London UK
PRESS RELEASE
ViiV Healthcare launches eighth phase III study in two-drug regimen
programme for HIV-1 treatment
TANGO study will investigate dolutegravir (TIVICAY) and lamivudine
(EPIVIR) in patients with HIV who have achieved viral
suppression on
a tenofovir alafenamide fumarate-based regimen
London, UK 8 February 2018 - Today ViiV Healthcare, the global specialist HIV
company majority owned by GSK, with Pfizer Inc. and Shionogi
Limited as shareholders, announced the start of a phase III study
designed to establish if adults with HIV-1 with current virologic
suppression on a tenofovir alafenamide fumarate (TAF)-based regimen
of at least three drugs are able to maintain viral suppression upon
switching to a two-drug regimen (2DR) of dolutegravir (TIVICAY) and
lamivudine (EPIVIR). TANGO will seek to enrol approximately 550
adults with HIV-1, from clinical trial sites in North America,
Europe, Australia, and Japan.
HIV care is a long-term prospect for those living with the disease,
requiring life-long adherence to treatment. Since the introduction
of highly active antiretroviral therapy 20 years ago, HIV treatment
regimens have predominantly included three antiretroviral
drugs.[1],[2]
ViiV Healthcare is
looking to the future and exploring how HIV treatment could evolve
to reduce the number of drugs to which a patient is exposed, while
maintaining the level of efficacy achieved with three-drug
regimens.
John C
Pottage, Jr, MD, Chief Scientific and Medical Officer, ViiV
Healthcare, said: "We are asking a
simple question in the TANGO study - can virally suppressed people
with HIV reduce the number of medicines in their HIV treatment
regimen while maintaining viral suppression? If the data show the
answer to be yes, this may allow healthcare providers to address
issues of long-term toxicity by reducing exposure to antiviral
agents over a lifetime of treatment. We believe that with its high
barrier to resistance, dolutegravir has the right clinical profile
to be a core part of 2DRs for the treatment of HIV-1 and look
forward to seeing the results of TANGO in
2019."
The TANGO trial is designed to demonstrate the non-inferior
antiviral activity of switching to dolutegravir and lamivudine
compared to continuation of a TAF-based regimen over 48 weeks in
virologically suppressed subjects. TANGO will characterise patient
satisfaction as well as the long-term antiviral activity,
tolerability and safety of a 2DR of dolutegravir and lamivudine
through to 96 weeks.
The TANGO study follows the GEMINI studies' investigation of the
2DR of dolutegravir and lamivudine in treatment-naïve patients
with HIV-1. Results from those trials are anticipated later this
year.
TIVICAY and EPIVIR are trademarks owned by or licensed to the ViiV
Healthcare group of companies.
Notes to editors
About TANGO (this study does not yet have
an NCT number)
TANGO is a phase III, randomised, open-label, active-controlled,
multicentre, parallel-group study to assess the non-inferior
antiviral activity and safety of a two-drug regimen of dolutegravir
and lamivudine compared to continuation on a TAF-based regimen in
HIV-infected adults who are virologically suppressed and stable on
a TAF-based regimen. Approximately 550 HIV-1 infected adults who
are on a stable TAF-based regimen will be randomised 1:1 to switch
to dolutegravir and lamivudine once daily for up to 96
weeks, or to continue their
TAF-based regimen for 48 weeks. For patients in the TAF-based arm,
if the HIV-1 RNA is <50 c/ml at the Week 48 visit, these
study
participants will switch to dolutegravir and lamivudine for the
remainder of the study.
The primary endpoint for the study is the proportion of
participants who meet the Snapshot virologic failure criteria at
Week 48 using the Intent-to-Treat Exposed (ITT-E)
population.
Other studies in ViiV Healthcare's phase III 2DR
programme:
SWORD 1 and 2 (NCT02429791 and NCT02422797) - Two identical
studies evaluating the safety and efficacy of switching
virologically suppressed patients from a three- or four-drug
antiretroviral regimen to a two-drug regimen of dolutegravir and
rilpivirine (Janssen Sciences Ireland UC). Results presented at
CROI 2017.
GEMINI 1 and 2 (NCT02831673 and NCT02831764)
- Two
identical studies comparing a two-drug regimen of dolutegravir plus
lamivudine with a three-drug regimen of dolutegravir plus the
fixed-dose tablet tenofovir/emtricitabine in treatment-naïve
adults living with HIV. Results are anticipated in
2018.
ATLAS (NCT02951052) - Study evaluating the efficacy and
safety of a two-drug regimen of long-acting, injectable
cabotegravir and rilpivirine (Janssen Sciences Ireland UC)
administered every 4 weeks compared to continuation of current ART
of two nucleoside reverse transcriptase inhibitors (NRTIs) plus an
integrase inhibitor (INI), non-nucleoside reverse transcriptase
inhibitor (NNRTI) or protease inhibitor (PI). Results are
anticipated in 2018.
FLAIR (NCT02938520) - Study evaluating the safety and
efficacy of a two-drug regimen of intramuscular, long-acting,
injectable cabotegravir and rilpivirine (Janssen Sciences Ireland
UC) administered every four weeks in treatment-naïve adults
living with HIV. Results are anticipated in 2018.
ATLAS 2M (NCT03299049) - Study
evaluating the safety and efficacy of long-acting cabotegravir and
long-acting rilpivirine (Janssen Sciences Ireland UC) administered
every 8 weeks compared to long-acting cabotegravir and long-acting
rilpivirine (Janssen Sciences Ireland UC) administered every 4
weeks. Results are anticipated in 2019.
About EPIVIR
Lamivudine is a nucleoside analogue used in combination with other
antiretroviral agents for the treatment of HIV infection.
Lamivudine is available in branded (EPIVIR) and generic
forms.
About TIVICAY (dolutegravir)
Dolutegravir (TIVICAY) is an integrase strand transfer inhibitor
(INSTI) for use in combination with other antiretroviral agents for
the treatment of HIV. Integrase inhibitors block HIV replication by
preventing the viral DNA from integrating into the genetic material
of human immune cells (T-cells). This step is essential in the HIV
replication cycle and is also responsible for establishing chronic
infection. Tivicay is approved in over 100 countries across North
America, Europe, Asia, Australia, Africa and Latin
America.
TIVICAY (dolutegravir) tablets
Professional Indication(s) and Important Safety
Information
Indications and Usage
TIVICAY is a human immunodeficiency virus type 1 (HIV-1) integrase
strand transfer inhibitor (INSTI) indicated in combination
with:
● other antiretroviral agents for the treatment of
HIV-1 infection in adults and pediatric patients weighing at least
30 kg
● rilpivirine as a complete regimen for the
treatment of HIV-1 infection in adults to replace the current
antiretroviral regimen in those who are virologically suppressed
(HIV-1 RNA < 50 copies per mL) on a stable antiretroviral
regimen for ≥6 months with no history of treatment failure or
known substitutions associated with resistance to either
antiretroviral agent
Important Safety Information
CONTRAINDICATIONS:
TIVICAY is contraindicated in patients:
● with previous hypersensitivity reaction to
dolutegravir
● receiving dofetilide
(antiarrhythmic)
WARNINGS AND PRECAUTIONS:
Hypersensitivity Reactions:
● Hypersensitivity reactions have been reported and
were characterized by rash, constitutional findings, and sometimes
organ dysfunction, including liver injury. The events were reported
in <1% of subjects receiving TIVICAY in Phase 3 clinical
trials
● Discontinue TIVICAY and other suspect agents
immediately if signs or symptoms of hypersensitivity reactions
develop, as a delay in stopping treatment may result in a
life-threatening reaction. Monitor clinical status, including liver
aminotransferases, and initiate appropriate therapy if
hypersensitivity reaction is suspected
Hepatotoxicity:
● Patients with underlying hepatitis B or C may be
at increased risk for worsening or development of transaminase
elevations with use of TIVICAY. In some cases the elevations in
transaminases were consistent with immune reconstitution syndrome
or hepatitis B reactivation, particularly in the setting where
anti-hepatitis therapy was withdrawn
● Cases of hepatic toxicity, including elevated
serum liver biochemistries, hepatitis, and acute liver failure,
have also been reported in patients receiving a
dolutegravir-containing regimen who had no pre-existing hepatic
disease or other identifiable risk factors. Drug-induced liver
injury leading to liver transplant has been reported with TRIUMEQ
(abacavir, dolutegravir, and lamivudine)
● Monitoring for hepatotoxicity is
recommended
Risk of Adverse Reactions or Loss of Virologic Response Due to Drug
Interactions:
The concomitant use of TIVICAY and other drugs may result in known
or potentially significant drug interactions (see Contraindications
or Drug Interactions).
Immune Reconstitution Syndrome,
including the occurrence of autoimmune disorders with variable time
to onset, has been reported.
ADVERSE REACTIONS:
The most commonly reported (≥2%) adverse reactions of
moderate to severe intensity in treatment-naïve adult subjects
in any one trial receiving TIVICAY in a combination regimen were
insomnia (3%), fatigue (2%), and headache (2%).
DRUG INTERACTIONS:
● Coadministration of TIVICAY with certain inducers
of UGT1A and/or CYP3A may reduce plasma concentrations of
dolutegravir and require dose adjustments of
TIVICAY
● Administer TIVICAY 2 hours before or 6 hours after
taking polyvalent cation-containing antacids or laxatives,
sucralfate, oral supplements containing iron or calcium, or
buffered medications. Alternatively, TIVICAY and supplements
containing calcium or iron can be taken with
food
● Consult the full Prescribing Information for
TIVICAY for more information on potentially significant drug
interactions, including clinical comments
USE IN SPECIFIC POPULATIONS:
Pregnancy:
There are insufficient human data on the use of TIVICAY during
pregnancy to inform a drug-associated risk of birth defects and
miscarriage. An Antiretroviral Pregnancy Registry has been
established.
Lactation:
Breastfeeding is not recommended due to the potential for HIV
transmission and developing viral resistance in HIV-positive
infants.
Pediatric Use:
Safety and efficacy of TIVICAY have not been established in
pediatric patients weighing less than 30 kg or in any pediatric
patients who are INSTI-experienced.
EPIVIR (lamivudine) tablets
Important Safety Information (ISI)
The following ISI is based on the Highlights section of the US
Prescribing Information for EPIVIR. Please consult the
full Prescribing Information for all the labeled safety information
for EPIVIR.
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
EPIVIR safely and effectively. See
full prescribing information for EPIVIR.
EPIVIR (lamivudine) tablets for oral use
WARNING: LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY, EXACERBATIONS OF
HEPATITIS B, and DIFFERENT FORMULATIONS OF EPIVIR
See full prescribing information for complete boxed
warning.
● Lactic acidosis and severe
hepatomegaly with steatosis, including fatal cases, have been
reported with the use of nucleoside analogues.
● Severe acute exacerbations of
hepatitis B have been reported in patients who are co-infected with
hepatitis B virus (HBV) and human immunodeficiency virus (HIV-1)
and have discontinued EPIVIR. Monitor hepatic function closely in
these patients and, if appropriate, initiate anti-hepatitis B
treatment.
● Patients with HIV-1 infection
should receive only dosage forms of EPIVIR appropriate for
treatment of HIV-1.
INDICATIONS AND USAGE
EPIVIR is a nucleoside analogue reverse transcriptase inhibitor
indicated in combination with other antiretroviral agents for the
treatment of HIV-1 infection.
Limitations
of Use: The dosage of this product is for HIV-1 and not for
HBV.
DOSAGE AND ADMINISTRATION
●
Adults: 300 mg daily, administered as
either 150 mg twice daily or 300 mg once daily.
●
Pediatric Patients Aged 3 Months and
Older: Administered either once or twice daily. Dose should be
calculated on body weight (kg) and should not exceed 300 mg
daily.
●
Patients with Renal Impairment: Doses
of EPIVIR must be adjusted in accordance with renal
function.
DOSAGE FORMS AND STRENGTHS
●
Tablets: 150 mg,
scored.
●
Tablets: 300 mg.
●
Oral Solution: 10 mg per
mL.
CONTRAINDICATIONS
●
EPIVIR is contraindicated in patients
with previous hypersensitivity reaction to
lamivudine.
WARNINGS AND PRECAUTIONS
● Co-infected HIV-1/HBV Patients: Emergence of
lamivudine-resistant HBV variants associated with
lamivudine-containing antiretroviral regimens has been
reported.
● Hepatic decompensation, some fatal, has occurred
in HIV-1/HCV co-infected patients receiving interferon and
ribavirin-based regimens. Monitor for treatment-associated
toxicities. Discontinue EPIVIR as medically appropriate and
consider dose reduction or discontinuation of interferon alfa,
ribavirin, or both.
● Pancreatitis: Use with caution in pediatric
patients with a history of pancreatitis or other significant risk
factors for pancreatitis. Discontinue treatment as clinically
appropriate.
● Immune reconstitution syndrome and
redistribution/accumulation of body fat have been reported in
patients treated with combination antiretroviral
therapy.
● Lower virologic suppression rates and increased
risk of viral resistance were observed in pediatric subjects who
received EPIVIR oral solution concomitantly with other
antiretroviral oral solutions compared with those who received
tablets. An all-tablet regimen should be used when
possible.
ADVERSE REACTIONS
●
The most common reported adverse reactions (incidence
greater than or equal to 15%) in adults were headache, nausea,
malaise and fatigue, nasal signs and symptoms, diarrhea, and
cough.
● The most common reported adverse reactions
(incidence greater than or equal to 15%) in pediatric subjects were
fever and cough.
To report SUSPECTED ADVERSE
REACTIONS, contact ViiV Healthcare at 1-888-844-8872 or FDA at
1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
●
Sorbitol: Coadministration of lamivudine and sorbitol
may decrease lamivudine concentrations; when possible, avoid
chronic coadministration.
USE IN SPECIFIC POPULATIONS
●
Lactation: Breastfeeding
not recommended.
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 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.
GSK - 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
|
ViiV
Healthcare Media enquiries:
|
Stephen
Rea
|
+1 215
751 4394
|
|
|
Marc
Meachem
|
+1 919
483 8756
|
|
|
|
|
|
GSK
Global Media enquiries:
|
Simon
Steel
|
+44 (0)
20 8047 5502
|
|
|
David
Daley
|
+44 (0)
20 8047 5502
|
|
|
|
|
|
Analyst/Investor
enquiries:
|
Sarah
Elton-Farr
|
+44 (0)
20 8047 5194
|
|
|
Tom
Curry
|
+ 1 215
751 5419
|
|
|
Gary
Davies
|
+44 (0)
20 8047 5503
|
|
|
James
Dodwell
|
+44 (0)
20 8047 2406
|
|
|
Jeff
McLaughlin
|
+1 215
751 7002
|
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 2016.
[1] Guidelines for the Use of Antiretroviral Agents in
HIV-1-Infected Adults and Adolescents; p. F-4. Available
at www.aidsinfo.nih.gov/guidelines Last
accessed February 2018
[2] Consolidated
guidelines on the use of antiretroviral drugs for treating and
preventing HIV infection: Recommendations for a public health
approach - Second edition. WHO June 2016; p. 97. Available
at
http://www.who.int/hiv/pub/arv/arv-2016/en/ Last
accessed February 2018
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)
|
|
|
|
|
Date: February
08, 2018
|
|
|
|
|
|
|
By: VICTORIA
WHYTE
--------------------------
|
|
|
|
|
|
Victoria Whyte
|
|
|
Authorised
Signatory for and on
|
|
|
behalf
of GlaxoSmithKline plc
|