ViiV Healthcare Launches Phase III Programme Evaluating a Two-drug Regimen Combining Dolutegravir and Lamivudine for HIV-1 Treatment

London (ots/PRNewswire) -

ViiV Healthcare today announced the start of a phase III programme
to support regulatory filings for a two-drug regimen of dolutegravir
(Tivicay®) and lamivudine (Epivir®) as a treatment for HIV-1
infection in adults who have not received prior antiretroviral
therapy.

(Logo: http://photos.prnewswire.com/prnh/20160223/336449LOGO )

The phase III programme comprises two identical studies (GEMINI 1
and 2) comparing a two-drug regimen of dolutegravir plus lamivudine
with a three-drug regimen of dolutegravir plus the fixed-dose tablet
tenofovir/emtricitabine (Truvada®). The studies together will include
approximately 1,400 men and women living with HIV and are being
conducted at research centres in Europe, Central and South America,
North America, South Africa and Asia Pacific.

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 drug exposure
and improve treatment adherence, while maintaining the level of
efficacy achieved with three-drug regimens.

John C Pottage, Jr, MD, Chief Scientific and Medical Officer, ViiV
Healthcare, commented, "We believe the clinical profile for
dolutegravir presents an important opportunity to investigate the
possibility of first-line treatment of HIV with a two-drug regimen.
With this ambitious phase III programme, we will explore whether this
two-drug regimen can fundamentally change the existing HIV treatment
strategy, reducing the number of medications and potentially
streamlining treatment regimens for people living with HIV."

The GEMINI trials are the third development programme undertaken
by ViiV Healthcare to investigate a two-drug regimen for the
treatment of HIV.

Notes to editors

GEMINI 1 & 2: Study design

Each study is a randomised, double-blind study and will compare
the safety, efficacy, and tolerability of a two-drug regimen of
dolutegravir plus lamivudine administered once daily, against
dolutegravir plus two nucleoside reverse transcriptase inhibitors
(tenofovir/emtricitabine fixed-dose combination) administered once
daily in HIV-1 infected adult subjects that have not previously
received antiretroviral therapy.

Each study will include approximately 700 subjects who will be
randomised 1:1 to receive dolutegravir plus lamivudine or
dolutegravir plus tenofovir/emtricitabine fixed-dose combination.
Both studies are designed to demonstrate the non-inferior antiviral
activity of a dolutegravir plus lamivudine regimen to that of
dolutegravir plus tenofovir/emtricitabine fixed-dose combination. The
primary efficacy endpoint will be measured at Week 48 and the study
will continue to evaluate the long term antiviral activity,
tolerability and safety of dolutegravir plus lamivudine through Week
148.

For more information please search for NCT02831673 (GEMINI 1) or
NCT02831764 (GEMINI 2) on http://www.clinicaltrials.gov.

Epivir® is a registered trademark of the ViiV Healthcare group of
companies.

Tivicay® is a registered trademark of the ViiV Healthcare group of
companies.

Truvada® is a registered trademark of Gilead Sciences, Inc.

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.

About lamivudine

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 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. 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 new
HIV medicines, as well as support communities affected by HIV. For
more information on the company, its management, portfolio, pipeline,
and commitment, please visit http://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 http://www.gsk.com.

TIVICAY® (dolutegravir) tablets

Professional Indication(s) and Important Safety Information

Note: this is taken from the US label and local variations apply.
Please refer to applicable local labelling

FDA 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.

Limitations of Use:

- Use of TIVICAY in INSTI-experienced patients should be guided by
the number and type of baseline INSTI substitutions. The efficacy
of TIVICAY 50 mg twice daily is reduced in patients with an
INSTI-resistance Q148 substitution plus 2 or more additional
INSTI-resistance substitutions including T66A, L74I/M, E138A/K/T,
G140S/A/C, Y143R/C/H, E157Q, G163S/E/K/Q, or G193E/R

Important Safety Information

Contraindications:

TIVICAY is contraindicated in patients:

- with previous hypersensitivity reaction to dolutegravir
- receiving dofetilide (antiarrhythmic)

Hypersensitivity Reactions:

- Hypersensitivity reactions have been reported and were
characterised 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

Effects on Serum Liver Biochemistries in Patients with Hepatitis B
or C Co-infection:

- 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
- Appropriate laboratory testing prior to initiating therapy and
monitoring for hepatotoxicity during therapy with TIVICAY are
recommended in patients with underlying hepatic disease such as
hepatitis B or C

Fat Redistribution or accumulation has been observed in patients
receiving antiretroviral therapy

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

Pregnancy: TIVICAY should be used during pregnancy only if the
potential benefit justifies the potential risk. An Antiretroviral
Pregnancy Registry has been established.

Nursing Mothers: Breastfeeding is not recommended due to the
potential for HIV transmission and the potential for adverse
reactions in nursing infants.

EPIVIR® (lamivudine) tablets

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 hepatitis B virus (HBV).

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.

BOXED 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 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.

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.

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.

USE IN SPECIFIC POPULATIONS

- Lactation: Breastfeeding not recommended.

1. Guidelines for the Use of Antiretroviral Agents in
HIV-1-Infected Adults and Adolescents; p. F-4. Available at
http://www.aidsinfo.nih.gov/guidelines Last accessed August 2016

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 August
2016

ots Originaltext: ViiV Healthcare
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