New Phase IIIb/IV Data Show Switching to Once-Daily Triumeq(R) Maintains HIV Viral Suppression

PR61909

LONDON, Sept. 23 / PRNewswire=KYODO JBN / --

    ViiV Healthcare today announced 24-week data from the Phase IIIb/IV

STRIIVING study, an open-label study evaluating the efficacy, safety and

tolerability of switching from an antiretroviral therapy (ART) to the

once-daily, fixed-dose dolutegravir-based regimen, Triumeq(R)

(abacavir/dolutegravir/lamivudine) in virologically suppressed adults with

HIV-1 (n=274).[1] The study included (n= 277) adults who remained on their

existing ART to 24 weeks. STRIIVING met its primary endpoint, demonstrating

that viral suppression was non-inferior for patients switching to

abacavir/dolutegravir/lamivudine (HIV RNA ＜50 copies/mL in intention to treat

efficacy (ITTe, primary endpoint; n=551): 85%

(abacavir/dolutegravir/lamivudine) vs. 88% (existing ART) [adjusted difference

-3.4%; 95% CI: -9.1, 2.3], per protocol (PP; n=435): 93% vs. 93% [adjusted

difference -0.3%; 95% CI: -4.9, 4.4]).[1] No patients had protocol defined

virologic failure (confirmed plasma HIV-1 RNA greater than or equal to400

copies/mL) and therefore no patients were evaluated for treatment-emergent

resistance in either arm (ITTe).[1]

    Furthermore, statistically, the treatment satisfaction score improved

significantly more for those patients switching to once-daily

abacavir/dolutegravir/lamivudine from their established regimen, as assessed by

the HIV Treatment Satisfaction Questionnaire (adjusted difference 2.4, 95% CI:

1.3, 3.5; p＜0.001).[1]

    "For clinicians, choosing among antiretroviral therapies now involves

balancing efficacy with factors such as tolerability, dosing, ability to use

with other medications, and resistance profile. These data support the use of

once-daily abacavir/dolutegravir/lamivudine as a treatment option in the switch

setting for appropriate patients," said John Pottage, MD, Chief Scientific and

Medical Officer, ViiV Healthcare.

    The STRIIVING study recruited patients switching from a broad range of

protease inhibitor (PI; n=234), integrase strand transfer inhibitor (INSTI;

n=146) and non-nucleoside reverse transcriptase inhibitor (NNRTI; n=171)-based

regimens, with the aim of reflecting a common clinical situation.[1]

    Patients switching to abacavir/dolutegravir/lamivudine reported more

adverse events (AEs) leading to withdrawal compared with those who continued on

their established regimen (ITTe: 4% vs. 0%).[1] The majority of these AEs were

Grade I & 2.[1] The most common AEs (greater than or equal to 5%) reported in

patients switched to the abacavir/dolutegravir/lamivudine arm included cough

(5%), diarrhoea (7%), fatigue (7%), headache (5%), nausea (10%) and upper

respiratory tract infection (7%).[1] The AE profile observed with

abacavir/dolutegravir/lamivudine in the study is in line with previous studies

with dolutegravir-based regimens.[2],[3],[4],[5],[6]

    STRIIVING study design

    STRIIVING is a Phase IIIb/IV randomised, open-label, multicentre, North

American study to evaluate the efficacy, safety and tolerability of switching

from an ART regimen to once-daily, fixed-dose abacavir/dolutegravir/lamivudine

in virologically-suppressed (HIV-1 RNA ＜50 copies/mL) adults with HIV-1.

Participants were randomised 1:1 to switch to abacavir/dolutegravir/lamivudine

(n=274) or continue on their current ART (n=277) for 24 weeks. The total number

of patients in the study was 551.[1]

    Important Safety Information (ISI) for Triumeq(R) (abacavir, dolutegravir

and lamivudine) tablets  

    The following ISI is based on the Highlights section of the Prescribing

Information for Triumeq. Please consult the full Prescribing Information for

all the labelled safety information for Triumeq.

    BOXED WARNING: RISK OF HYPERSENSITIVITY REACTIONS, LACTIC ACIDOSIS AND

SEVEREHEPATOMEGALY, AND EXACERBATIONS OF HEPATITIS B

    See full Prescribing Information for complete boxed warning.

    - Serious and sometimes fatal hypersensitivity reactions have been

      associated with abacavir-containing products.

    - Hypersensitivity to abacavir is a multi-organ clinical syndrome.

    - Patients who carry the HLA-B*5701 allele are at high risk for

      experiencing a hypersensitivity reaction to abacavir.

    - Discontinue Triumeq as soon as a hypersensitivity reaction is suspected.

      Regardless of HLA-B*5701 status, permanently discontinue Triumeq if

      hypersensitivity cannot be ruled out, even when other diagnoses are

      possible.

    - Following a hypersensitivity reaction to abacavir, NEVER restart Triumeq

      or any other abacavir-containing product.

    - 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 lamivudine, a

      component of Triumeq. Monitor hepatic function closely in these patients

      and, if appropriate, initiate anti-hepatitis B treatment.

    CONTRAINDICATIONS  

    - Presence of HLA-B*5701 allele.

    - Previous hypersensitivity reaction to abacavir, dolutegravir or

      lamivudine.

    - Co-administration with dofetilide.

    - Moderate or severe hepatic impairment.

    WARNINGS AND PRECAUTIONS

    Patients with underlying hepatitis B or C may be at increased risk for

worsening or development of transaminase elevations with use of Triumeq.

Appropriate laboratory testing prior to initiating therapy and monitoring for

hepatotoxicity during therapy with Triumeq is recommended in patients with

underlying hepatic disease such as hepatitis B or C.

    - Hepatic decompensation, some fatal, has occurred in HIV-1/Hepatitis C

      Virus (HCV) co-infected patients receiving combination antiretroviral

      therapy and interferon alfa with or without ribavirin. Discontinue

      Triumeq as medically appropriate and consider dose reduction or

      discontinuation of interferon alfa, ribavirin, or both.

    - Immune reconstitution syndrome and redistribution/accumulation of body

      fat have been reported in patients treated with combination

      antiretroviral therapy.

    - Administration of Triumeq is not recommended in patients receiving other

      products containing abacavir or lamivudine.

    ADVERSE REACTIONS

    The most commonly reported (greater than or equal to2%) adverse reactions

of at least moderate intensity in treatment-naive adult subjects receiving

Triumeq were insomnia (3%), headache (2%), and fatigue (2%).

    DRUG INTERACTIONS

    Co-administration of Triumeq with other drugs can alter the concentration

of other drugs and other drugs may alter the concentrations of Triumeq. The

potential drug-drug interactions must be considered prior to and during therapy.

    USE IN SPECIFIC POPULATIONS  

    - Pregnancy: Triumeq should be used during pregnancy only if the potential

      benefit justifies the potential risk.

    - Nursing mothers: Breastfeeding is not recommended due to the potential

      for HIV transmission.

    - Triumeq is not recommended in patients with creatinine clearance less

      than 50 mL per min.

    If a dose reduction of abacavir, a component of Triumeq, is required for

patients with mild hepatic impairment, then the individual components should be

used.

    About Triumeq(R)

    Triumeq is a once-daily dolutegravir-based regimen, containing the

integrase strand transfer inhibitor (INSTI) dolutegravir and the nucleoside

reverse transcriptase inhibitors (NRTIs) abacavir and lamivudine.

    Two essential steps in the HIV life cycle are replication - when the virus

turns its RNA copy into DNA - and integration - the moment when viral DNA

becomes part of the host cell's DNA. These processes require two enzymes called

reverse transcriptase and integrase. NRTIs and INSTIs interfere with the action

of the two enzymes to prevent the virus from replicating. This decrease in

replication will lead to less virus being available to cause subsequent

infection of uninfected cells.

    Please refer to the full US Prescribing Information for contraindications,

special warnings and precautions for use. [7]

    Triumeq is a registered trademark of the ViiV Healthcare group of companies.

    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

    References

    1. Trottier B, Lake J, Logue K et al. Switching to

Abacavir/Dolutegravir/Lamivudine combination (ABC/DTG/3TC FDC) from a PI, INI

or NNRTI based regimen maintains HIV suppression.  Presented at the

Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), 17-21

September 2015, San Diego, California  

    2. Raffi F, Jaeger H, Quiros-Roldan E, Albrecht H, Belonosova E, Gatell JM,

Baril J-G, Domingo P, Brennan C, Almond S, Min S, for the SPRING-2 Study Group.

Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive

adults with HIV-1 infection (SPRING-2 study): 96 week results from a

randomised, double-blind, non-inferiority trial. Lancet Infect Dis.

2013;13(11):927-935.

    3. Pappa K, Baumgarten A, Felizarta F, et al. Dolutegravir (DTG) +

abacavir/lamivudine once daily superior to tenofovir/emtricitabine/efavirenz in

treatment naive HIV subjects: 144-week results from SINGLE (ING114467).

Abstract presented at: 54th Interscience Conference on Antimicrobial Agents and

Chemotherapy; September 5-9, 2014; Washington, DC, USA.

    4. Castagna S, et al. Dolutegravir in antiretroviral-experienced patients

with raltegravir- and/or elvitegravir-resistant HIV-1: 24-week results of the

Phase III VIKING-3 study. J Infect Dis 2014;210:354-62

    5. Vavro C, Huang J, Avatapally C, Min S, Ait-Khaled M. Durable efficacy

and limited integrase resistance in subjects receiving dolutegravir after

failing a prior regimen: week 48 results from VIKING-3. Rev Antiviral Ther

Infect Dis. 2014;2:Abstract O-10.

    6. Molina J, et al. Once-daily dolutegravir versus darunavir plus ritonavir

for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results

from a randomised, open-label, phase 3b study. Lancet HIV 2015. Published

online March 2015 http://dx.doi.org/10.1016/S2352-3018(15)00027-2 (Last

Accessed March 2015)

    7. Triumeq US label

    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 'Risk factors' in the company's Annual Report on Form 20-F for 2014.

Source: ViiV Healthcare