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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 24 July
2018
GlaxoSmithKline plc
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(Address
of principal executive offices)
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by check mark whether the registrant files or
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Securities
Exchange Act of 1934.
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No x
Issued:
Tuesday 24 July 2018, London UK - LSE Announcement
ViiV Healthcare announces SWORD 100-week data for Juluca
(dolutegravir/rilpivirine) at AIDS 2018
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Juluca, the first 2-drug regimen, once daily, single pill regimen,
maintains viral suppression through 100 weeks
London, 24 July 2018 - ViiV Healthcare today presented
100-week results from its phase III programme evaluating the safety
and efficacy of switching virologically-suppressed people living
with HIV from a three or four-drug antiretroviral regimen to a
2-drug regimen of dolutegravir (ViiV Healthcare) and rilpivirine
(Janssen Sciences Ireland UC, part of the Janssen Pharmaceutical
Companies of Johnson & Johnson.)1 These results were
presented at the 22nd International AIDS Conference taking place
23-27 July 2018 in Amsterdam.
John C.
Pottage, Jr., MD, Chief Scientific and Medical Officer, ViiV
Healthcare, commented, "As we progress further into a new era of
HIV treatment, these 100-week data from the SWORD studies add to
the growing evidence base for Juluca and 2-drug regimens. The
results confirm the ability of Juluca to maintain efficacy over a
100-week period and importantly support that the long-term safety
profile of this regimen is consistent with the respective labels of
the component medicines. This 100-week data should provide
physicians with further confidence that they may be able to reduce
the number of antiretroviral drugs required to effectively maintain
virologic suppression in their patient's HIV."
In
pooled data from the SWORD 1 and SWORD 2 studies, 89% (456/513) of
participants on the 2-drug regimen of dolutegravir and rilpivirine
for 100 weeks (n=513) maintained viral suppression, with a viral
load of less than 50 copies/mL. A low rate of snapshot virologic
non-response was observed (n=13; 3%) and 6 participants met the
confirmed virologic withdrawal criterion. Three participants failed
with NNRTI mutations, one that had pre-existing NNRTI mutations at
baseline developed resistance to rilpivirine and was withdrawn; no
participants developed integrase inhibitor resistance. There were
no new safety findings in the second year of the study. A total 34
participants (7%) experienced adverse events that led to withdrawal
through week 100.1
In the
'late switch' arm (n=477), where participants continued on their
current antiretroviral regimen until week 52 before switching to
the 2-drug regimen of dolutegravir and rilpivirine, 93% (n=444) of
participants maintained viral suppression through week 100. Two
participants (<1%) met the confirmed virologic withdrawal
criterion, and the safety profile of the late switch group was
comparable to the early switch group (dolutegravir and rilpivirine
from day 1 to week 100). 30 participants (6%) experienced serious
adverse events and 15 participants (3%) experienced adverse events
that led to withdrawal.1
The
SWORD clinical programme is part of ViiV Healthcare's ongoing
commitment to lessening the burden of HIV treatment on PLHIV
through research into 2-drug regimens. The 48-week results from the
SWORD studies were presented at CROI 2017 and later published in
The Lancet.2 Data from the
SWORD studies as well as a pivotal bioequivalence study3 has led to
successful regulatory approval of the 2-drug regimen in the United
States, European Union, Canada and Australia, marketed under the
trade name Juluca.4,5,6,7
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Ends -
Notes to editors
About HIV
HIV
stands for the Human Immunodeficiency Virus. Unlike some other
viruses, the human body cannot get rid of HIV, so once someone has
HIV they have it for life. There is no cure for HIV, but effective
treatment can control the virus so that people with HIV can enjoy
healthy and productive lives.
HIV has
largely become a chronic treatable disease with improved access to
antiretroviral treatment. This has led to a 22% drop in global HIV
mortality between 2009 and 2013,8 but more can be done
for the estimated 36.7 million people living with HIV9 of which 160,000
were newly diagnosed in the Europe region alone in
2016.10
About Juluca (dolutegravir/rilpivirine)
Juluca
is ViiV Healthcare's first two-drug regimen (2DR), once-daily,
single-pill that combines dolutegravir 50mg (ViiV Healthcare), the
most widely prescribed integrase inhibitor (INI) worldwide, with
the nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine
25mg (Janssen Sciences Ireland UC). Juluca was granted marketing
authorisation by regulatory authorities in the United States in
November 2017, the European Union and Canada in May 2018, and
Australia in June 2018.4,5,6,7 ViiV
Healthcare has also submitted regulatory marketing applications in
other countries worldwide.
Juluca
is indicated for the treatment of human immunodeficiency virus type
1 (HIV-1) infection in adults who are virologically suppressed
(HIV-1 RNA < 50 copies/mL) on a stable antiretroviral regimen
for at least six months with no history of virological failure and
no known or suspected resistance to any NNRTI or INI.4
Two
essential steps in the HIV life cycle include reverse transcription
- when the virus turns its RNA (ribonucleic acid) copy into DNA
(deoxyribonucleic acid) - and integration - the moment when viral
DNA becomes part of the host cell's DNA. These processes require
two enzymes called nucleoside reverse transcriptase and integrase.
NNRTIs and INIs interfere with the action of these two enzymes to
prevent the virus from replicating. This decrease in replication
can lead to less virus being available to cause subsequent
infection of uninfected cells.
About the SWORD phase III programme for Juluca
The
SWORD phase III programme evaluates the efficacy, safety, and
tolerability of switching to dolutegravir plus rilpivirine from
current integrase inhibitor-, non-nucleoside reverse transcriptase
inhibitor-, or boosted protease inhibitor-based antiretroviral
regimen in HIV-1-infected adults who are virologically suppressed
with a three or four-drug regimen.11,12 SWORD-1
(NCT02429791) and SWORD-2 (NCT02422797) are replicate 148-week,
randomised, open-label, non-inferiority studies to assess the
antiviral activity and safety of a 2-drug, daily oral regimen of
dolutegravir plus rilpivirine compared with current antiretroviral
therapy11,12 (the 148-week
data will be shared in 2019). In the SWORD clinical trials,
dolutegravir and rilpivirine are provided as individual
tablets.11,12
The
primary endpoint is the proportion of patients with plasma HIV-1
RNA <50 copies per millilitre (copies/mL) at week 48. Key
secondary endpoints include evaluation of the development of viral
resistance, measurements of safety and tolerability, and changes in
renal, bone and cardiovascular biomarkers. The studies also include
exploratory measures to assess change in health-related quality of
life, willingness to switch and adherence to treatment
regimens.11,12
For more information on the trials please visit www.clinicaltrials.gov.
Juluca
and Tivicay are trademarks owned by the ViiV Healthcare group of
companies.
Edurant
is a registered trademark of Janssen Sciences Ireland
UC.
U.S. IMPORTANT SAFETY INFORMATION: JULUCA (dolutegravir and rilpivirine)
tablets
Professional Indication(s) and Important Safety
Information
Indication and Usage for JULUCA
JULUCA
is indicated as a complete regimen for the treatment of human
immunodeficiency virus type 1 (HIV-1) infection in adults to
replace the current antiretroviral regimen in those who are
virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable
antiretroviral regimen for ≥6 months with no history of
treatment failure and no known substitutions associated with
resistance to the individual components of JULUCA.
Important Safety Information
CONTRAINDICATIONS
JULUCA
is contraindicated in patients:
●
with previous
hypersensitivity reaction to dolutegravir or
rilpivirine.
●
receiving
dofetilide, carbamazepine, oxcarbazepine, phenobarbital, phenytoin,
rifampin, rifapentine, systemic dexamethasone (>1 dose), St.
John's wort, and proton pump inhibitors (e.g., esomeprazole,
lansoprazole, omeprazole, pantoprazole, and
rabeprazole).
WARNINGS AND PRECAUTIONS
Skin and Hypersensitivity Reactions:
●
Hypersensitivity reactions have been reported with dolutegravir and
were characterized by rash, constitutional findings, and sometimes
organ dysfunction, including liver injury. These events were
reported in <1% of subjects receiving dolutegravir in Phase 3
clinical trials.
●
Severe skin and hypersensitivity reactions have been reported
during postmarketing experience, including cases of Drug Reaction
with Eosinophilia and Systemic Symptoms (DRESS), with
rilpivirine-containing regimens and
have been accompanied by fever and/or organ dysfunctions
including elevations in hepatic serum biochemistries.
● Discontinue
JULUCA immediately if signs or symptoms of severe skin or
hypersensitivity reactions develop (such as severe rash or rash
accompanied by fever, general malaise, fatigue, muscle or joint
aches, blisters or peeling of the skin, mucosal involvement,
conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema,
and difficulty breathing), as a delay in stopping treatment
may result in a life-threatening reaction. Clinical status, including laboratory parameters
with liver aminotransferases, should be monitored and appropriate
therapy initiated.
Hepatotoxicity:
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Hepatic
adverse events have been reported, including cases of hepatic
toxicity, in patients without pre-existing hepatic disease or other
identifiable risk factors.
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Patients with underlying hepatitis B or C
or marked elevations in transaminases prior to treatment
may be at increased risk for worsening
or development of transaminase elevations. 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.
●
Monitoring for
hepatotoxicity is recommended.
Depressive Disorders:
●
Depressive
disorders (including depressed mood, depression, dysphoria, major
depression, mood altered, negative thoughts, suicide attempt, and
suicidal ideation) have been reported.
●
Promptly evaluate
patients with severe depressive symptoms.
Risk of Adverse Reactions or Loss of Virologic Response Due to Drug
Interactions:
●
The concomitant use
of JULUCA and other drugs may result in known or potentially
significant drug interactions, see Contraindications and Drug
Interactions sections. Rilpivirine doses 3 and 12 times higher than
the recommended dose can prolong the QTc interval. Consider
alternatives to JULUCA when coadministered with a drug with a known
risk of Torsade de Pointes. Consider the potential for drug
interactions prior to and during therapy with JULUCA and monitor
for adverse reactions.
ADVERSE REACTIONS: Most common adverse reactions with JULUCA
(incidence ≥2%, all Grades) were diarrhea (2%) and headache
(2%).
DRUG INTERACTIONS
●
Because JULUCA is a
complete regimen, coadministration with other antiretroviral
medications for the treatment of HIV-1 infection is not
recommended.
●
Drugs that induce
or inhibit CYP3A or UGT1A1 may affect the plasma concentrations of
the components of JULUCA.
●
Drugs that increase
gastric pH or containing polyvalent cations may decrease plasma
concentrations of the components of JULUCA.
●
Consider
alternatives to prescribing JULUCA with drugs with a known risk of
Torsade de Pointes.
●
Consult
the full Prescribing Information for JULUCA for more information on
potentially significant drug interactions, including clinical
comments.
USE IN SPECIFIC POPULATIONS
●
Pregnancy: There are
insufficient prospective pregnancy data to adequately assess the
risk of birth defects and miscarriage. An Antiretroviral Pregnancy
Registry has been established.
●
Lactation: Breastfeeding is
not recommended due to the potential for HIV-1 transmission and the
potential for adverse reactions in nursing infants.
DOSAGE AND ADMINISTRATION
●
Dosage: 1 tablet taken orally once daily
with a meal for adult patients.
●
Recommended
Dosage of JULUCA with Rifabutin Coadministration: Take an
additional 25-mg tablet of rilpivirine with JULUCA once daily with
a meal for the duration of the rifabutin
coadministration.
Full US prescribing information including is available
at:
https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Juluca/pdf/JULUCA-PI-PIL.PDF
For the EU Summary of Product Characteristics, please
visit:
https://www.medicines.org.uk/emc/product/9246
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.
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.
Cautionary statement regarding forward-looking statements
ViiV
Healthcare Limited, the global specialist HIV company, is majority
owned by GlaxoSmithKline plc, with Pfizer Inc. and Shionogi
Limited. 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.
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ViiV
Healthcare Media enquiries:
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Patricia
O'Connor
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+44 (0)
208 047 5982
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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
enquiries:
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Sarah
Elton-Farr
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+44 (0)
20 8047 5194
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Danielle
Smith
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+44 (0)
20 8047 0932
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James
Dodwell
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+44 (0)
20 8047 2406
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Jeff
McLaughlin
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+1 215
751 7002
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References
1 Aboud M, Orkin C,
Podzamczer D, et al. Durable Suppression 2 years after switch to
DTG+RPV 2-Drug Regimen: SWORD 1&2 Studies. Presented at the
22nd International AIDS Conference (AIDS 2018), 23-27 July 2018,
Amsterdam, The Netherlands.
2 Llibre JM, et al. Efficacy, safety, and tolerability
of dolutegravir-rilpivirine for the maintenance of virological
suppression in adults with HIV-1: phase 3, randomised,
non-inferiority SWORD-1 and SWORD-2 studies. The Lancet. 2018 Mar
3;391(10123):839-849.
3 Metha R, et al. Bioequivalence of a fixed dose
combination tablet of dolutegravir and rilpivirine in healthy
subjects. Presented at the 18th Workshop on Clinical Pharmacology
of Antiviral Therapy, 2017. Chicago, United States.
4 Juluca EU
Summary of Product Characteristics www.ema.europa.eu.
5 Juluca
(dolutegravir and rilpivirine) Prescribing Information. U.S
Approval 2017.
6 Health Canada. Juluca certified product information
document. 18 May 2018.
7 Australian Government. Department of Health Therapeutic
Goods Administration. Juluca Product Information - ARTG ID 291356.
Available at:
https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2018-PI-01956-1&d=2018062916114622483
Last accessed July 2018.
8 World Health Organization. Global Update on the
health sector response to HIV, 2014. July 2014. Available at:
http://apps.who.int/iris/bitstream/10665/128494/1/9789241507585_eng.pdf?ua=1 Last
accessed May 2018.
9 World Health Organization. HIV AIDS Factsheet 2017.
Available at: http://www.who.int/mediacentre/factsheets/fs360/en/
Last accessed July 2018.
10 World Health Organization. Infographic - Newly
diagnosed HIV infections in the WHO European Region, 2016.
Available at: http://www.euro.who.int/en/health-topics/communicable-diseases/hivaids/data-and-statistics/infographic-newly-diagnosed-hiv-infections-in-the-who-european-region,-2016 Last
accessed July 2018.
11 SWORD-1 -
Regimen Switch to Dolutegravir + Rilpivirine From Current
Antiretroviral Regimen in Human Immunodeficiency
Virus Type 1 Infected and Virologically Suppressed Adults
(SWORD-1). Available at: https://clinicaltrials.gov/ct2/show/NCT02429791?term=dolutegravir+AND+sword&cond=HIV&rank=3
Last accessed July 2018.
12 SWORD-2 -
Regimen Switch to Dolutegravir + Rilpivirine From Current
Antiretroviral Regimen in Human Immunodeficiency
Virus Type 1 Infected and Virologically Suppressed Adults
(SWORD-2). Available at: https://clinicaltrials.gov/ct2/show/NCT02422797?term=dolutegravir+AND+sword&cond=HIV&rank=1
Last accessed July 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.
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GlaxoSmithKline plc
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(Registrant)
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Date: July
24, 2018
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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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