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ViiV Healthcare Presents Phase III Data at AIDS 2018 from Landmark GEMINI Studies Showing Two-Drug Regimen of Dolutegravir and Lamivudine Has Similar Efficacy to a Three-Drug Regimen in Treatment Naïve HIV Patients, with No Emergence of Resistance

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GEMINI 1 & 2 studies meet primary endpoint, showing two-drug
regimen to be effective across high and low viral loads

ViiV Healthcare today presented at the 22nd International
AIDS conference in Amsterdam 48-week results from the phase III GEMINI 1
& 2 studies, assessing the safety and efficacy of a two-drug regimen
(2DR) of dolutegravir (DTG) and lamivudine (3TC) compared to a
three-drug regimen of dolutegravir and two nucleoside reverse
transcriptase inhibitors (NRTIs), tenofovir disoproxil
fumarate/emtricitabine (TDF/FTC), in treatment-naïve, HIV-1 infected
adults with baseline viral loads up to 500,000 copies per millilitre
(c/mL).

The studies met their primary endpoint for non-inferiority based on
plasma HIV-1 RNA <50c/mL, a standard measure of HIV control, at Week 48.
In a pooled analysis, 91% (655/716) of patients taking DTG + 3TC had
HIV-1 RNA <50 copies/mL compared with 93% (669/717) of patients taking
DTG +TDF/FTC [adjusted difference -1.7% (95% CI: -4.4%, 1.1%)].1

Pedro Cahn, principal investigator for the GEMINI study programme said:
"For the last 15-20 years, the standard of care for HIV has revolved
around three-drug regimens. Now that we have more potent drugs, the
focus is shifting to tolerability and convenience. The GEMINI studies
show that we can get the efficacy of three drugs in a two-drug regimen
with the tolerability and drug interaction profile of DTG and 3TC. These
are important findings for people living with HIV who will spend their
lifetime taking drugs to suppress their virus. The studies have the
potential to expand the treatment paradigm for first-line therapy of
people living with HIV."

Results show broadly consistent results for virus suppression across
individuals with higher viral load (more than 100,000 copies of viral
RNA per millilitre of blood plasma [>100,000 c/mL]) and lower viral load
(<=100,000 c/mL) HIV-1 plasma RNA. Rates of virologic failure were ≤1%
across all arms of the study. No patient who experienced virologic
failure in either treatment arm developed treatment-emergent resistance.1

The percentage of patients that withdrew due to adverse events was 2% in
each study arm (GEMINI 1 DTG + 3TC arm n=7, GEMINI 1 DTG + TDF/FTC arm
n=8, GEMINI 2 DTG + 3TC arm n= 8, GEMINI 2 DTG + TDF/FTC arm n=8).
Pooled results show that the most common (≥5%) adverse events across the
studies were headache, diarrhoea and nasopharyngitis in both arms (DTG +
3TC arm: 10%, 9%, and 8%, respectively, DTG + TDF/FTC: 10%, 11%, and
11%, respectively).1

Drug-related adverse events were less frequent in patients on the
DTG/3TC regimen (126/716, 18%), compared with those on the DTG + TDF/FTC
regimen (169/717, 24%).1

John C. Pottage, Jr., MD, Chief Scientific and Medical Officer of ViiV
Healthcare, said: "These data we have presented at AIDS 2018 provide
further evidence that we should be rethinking the traditional approach
to HIV treatment of using three or more drugs. The results from the
GEMINI programme support our belief that the two-drug regimen of
dolutegravir and lamivudine can be a valuable option for treatment-naïve
patients and that no patient should take more medicine than they need."

ViiV Healthcare intends to seek regulatory approval for a fixed-dose
combination of DTG and 3TC later this year. DTG and 3TC, as a 2DR, is
not yet approved for use by the US FDA.

- Ends -

Notes to editors

GEMINI 1 & 2 study design

The GEMINI studies are part of ViiV Healthcare's innovative clinical
trial programme, which seeks to increase the body of evidence supporting
the use of two-drug regimens for the treatment of HIV, in order to
ensure that no patient is taking more medication than they need. The
GEMINI studies are ongoing for 148 weeks.

GEMINI 1 (204861) and GEMINI 2 (205543) are duplicate, phase III,
randomised, double-blind, multicentre, parallel group, non-inferiority
studies. These studies evaluate a two-drug regimen of dolutegravir and
lamivudine compared with a three-drug, first-line regimen of DTG +
TDF/FTC in HIV-1 infected, antiretroviral therapy (ART)-naïve adult
participants with baseline HIV-1 viral loads up to 500,000 copies per
ml. The studies are designed to demonstrate the non-inferior efficacy,
safety, and tolerability of once-daily dolutegravir and lamivudine
compared to once-daily dolutegravir and the fixed-dose combination of
TDF/FDC at 48 weeks in HIV-1-infected, ART-naïve participants.

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

U.S INDICATIONS AND IMPORTANT SAFETY INFORMATION

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

U.S. 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: Tivicay (dolutegravir)

The following ISI is based on the Highlights section of the Prescribing
Information for Tivicay. Please consult the full Prescribing Information
for all the labelled safety information for Tivicay.

Contraindications

  • Previous hypersensitivity reaction to dolutegravir.
  • Coadministration with dofetilide.

Warnings and precautions

  • Hypersensitivity reactions characterized by rash, constitutional
    findings, and sometimes organ dysfunction, including liver injury,
    have been reported. 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.
  • Hepatotoxicity has been reported in patients receiving
    dolutegravir-containing regimens. Patients with underlying hepatitis B
    or C may be at increased risk for worsening or development of
    transaminase elevations. Monitoring for hepatoxicity is recommended.
  • Immune reconstitution syndrome has been reported in patients treated
    with combination antiretroviral therapy.

Adverse reactions

The most common adverse reactions of moderate to severe intensity and
incidence at least 2% (in those receiving TIVICAY in any one adult
trial) are insomnia, fatigue, and headache.

Drug interactions

  • Refer to the full prescribing information for important drug
    interactions with TIVICAY.
  • Drugs that are metabolic inducers may decrease the plasma
    concentrations of dolutegravir.
  • TIVICAY should be taken 2 hours before or 6 hours after taking
    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
    together with food.

Use in specific populations

  • Pregnancy: TIVICAY should be used during pregnancy only if the
    potential benefit justifies the potential risk.
  • Lactation: Breastfeeding is not recommended.

Full US prescribing information including is available at:

https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Tivicay/pdf/TIVICAY-PI-PIL.PDF

For the EU Summary of Product Characteristics, please visit:

https://www.medicines.org.uk/emc/medicine/28545

About Epivir® (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. Trademarks are owned by
or licensed to the ViiV Healthcare group of companies.

EPIVIR 300mg TABLETS

Professional Indication(s) and Important Safety Information

U.S. 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 HBV.

Important safety information (ISI): Epivir (lamivudine) tablets

The following ISI is based on the Highlights section of the Prescribing
Information for Epivir. Please consult the full Prescribing Information
for all the labelled safety information for Epivir.

Warning: Exacerbations of Hepatitis B, and different formulations of
Epivir

See full prescribing information for complete boxed warning.

  • 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.

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.
  • Lactic acidosis and severe hepatomegaly with steatosis, including
    fatal cases, have been reported with the use of nucleoside analogues.
  • 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. (5.4)
  • Immune reconstitution syndrome has 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.

Drug interactions

  • Sorbitol: Coadministration of lamivudine and sorbitol may decrease
    lamivudine concentrations; when possible, avoid chronic
    coadministration.

Use in specific populations

  • Lactation: Women infected with HIV should be instructed not to
    breastfeed due to potential for HIV transmission.

Full US prescribing information including is available at:

https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Epivir/pdf/EPIVIR-PI-PIL.PDF

For the EU Summary of Product Characteristics, please visit:

https://www.medicines.org.uk/emc/product/943

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.

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.

References

1 Cahn P, Sierra Madero J, Arribas J, et al. Non-Inferior
Efficacy of Dolutegravir (DTG) Plus Lamivudine (3TC) vs DTG Plus
Tenofovir/Emtricitabine (TDF/FTC) Fixed-Dose Combination in
Antiretroviral Treatment–Naive Adults With HIV-1 Infection—Week 48
Results From the GEMINI Studies. Presented at the 22nd International
AIDS Conference (AIDS 2018), 23-27 July 2018, Amsterdam, The Netherlands.

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