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

PR65392

LONDON, Aug. 16 2016 /PRNewswire=KYODO JBN/ --

     ViiV Healthcare today announced the start of a phase III programme to

support regulatory filings for a two-drug regimen of dolutegravir (Tivicay(R))

and lamivudine (Epivir(R)) 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(R)). 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(R) is a registered trademark of the ViiV Healthcare group of

companies.

    Tivicay(R) is a registered trademark of the ViiV Healthcare group of

companies.

    Truvada(R) is a registered trademark of Gilead Sciences, Inc.

    About Tivicay(R) (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(R)) 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(R) (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(R) 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 (greater than or equal to2%)

adverse reactions of moderate to severe intensity in treatment-naive 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(R) (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. ＜end_indent＞

    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

SOURCE: ViiV Healthcare