ViiV Healthcare Presents Positive Data from Phase IIIb/IV Study of Dolutegravir vs Darunavir in Treatment-Naive Adults with HIV

      ViiV Healthcare Presents Positive Data from Phase IIIb/IV Study of
        Dolutegravir vs Darunavir in Treatment-Naive Adults with HIV-1

PR Newswire

DENVER, Sept. 12, 2013

DENVER, Sept. 12,2013 /PRNewswire/ --ViiV Healthcare today announced initial
results from the Phase IIIb/IV FLAMINGO (ING114915) study. This open-label
study, for the first time, compared once-daily regimens containing 50mg
dolutegravir with once-daily regimens containing a protease inhibitor (PI)
(800mg darunavir boosted with 100mg ritonavir) in treatment-naive adults with
HIV-1. Both treatment arms were administered with investigator-selected dual
NRTIs. Non-inferiority was demonstrated at the 48-week time point between the
dolutegravir and darunavir-based regimens. A subsequent, pre-specified testing
procedure demonstrated statistical superiority in the dolutegravir treatment
arm.

At 48 weeks, a significantly greater proportion of the patients treated with
the dolutegravir regimen (90%) were virologically suppressed (HIV-1 RNA <50
copies/mL, the primary endpoint of the study per FDA snapshot) compared to
those treated with the darunavir regimen (83%, adjusted treatment difference
[95% CI] 7.1% (0.9%, 13.2%); P=0.025; N=242 in each arm). Comparing the
dolutegravir and darunavir arms, rates of virologic non-response were 6%
versus 7%, rates of treatment withdrawal due to adverse events were 1% versus
4%, and rates of treatment withdrawal for other reasons (such as protocol
deviation, lost to follow-up or consent withdrawn) were 2% versus 5%. There
were no treatment-emergent primary viral mutations leading to treatment
resistance in either study arm. These data were presented at the 53rd
International Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in
Denver, Colorado.^1

"These new clinical data are an important addition to our scientific
understanding of dolutegravir," said Dr John Pottage, Chief Medical Officer,
ViiV Healthcare. "This is the first study in our clinical programme to compare
dolutegravir to a boosted protease inhibitor in treatment-naive patients. PIs
are often selected as part of a first-line regimen for treatment-naive
patients, so these data provide important information regarding dolutegravir
as a treatment choice for these patients."

The most commonly (>10%) reported adverse events in either study arm were
diarrheoa (dolutegravir 17% vs boosted darunavir 29%), nausea (16% vs 18%),
and headache (15% vs 10%). Study participants on the dolutegravir regimen had
significantly fewer Grade 2 or higher abnormalities in fasting LDL-cholesterol
(dolutegravir 2% vs darunavir 7%, [p<0.001]). Serious adverse events (SAEs)
were reported among 11% and 5% of patients receiving a regimen containing
dolutegravir (N=242) or boosted darunavir (N=242), respectively, with one SAE
attributed by the investigator to dolutegravir treatment.

FLAMINGO (a Phase IIIb/IV study) follows four Phase III studies, which
examined the efficacy and safety of dolutegravir. It is the third study in
treatment-naive adults with HIV-1. Data from SPRING-2 (ING113086), SINGLE
(ING114467) and VIKING-3 (ING112574) were announced in 2012, and data from
SAILING (ING111762) were announced in 2013: these four studies formed the
basis of the registration package leading to the U.S. Food and Drug
Administration (FDA) approval of Tivicay^® on 12 August 2013. Please refer to
the full U.S. prescribing and patient information at:
https://www.viivhealthcare.com/media/58599/us_tivicay.pdf 

Important Information About Tivicay® (dolutegravir)
Indication 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
children aged 12 years and older and weighing at least 40 kg. The following
should be considered prior to initiating TIVICAY: poor virologic response was
observed in subjects treated with TIVICAY 50mg twice daily with an
INSTI-resistance Q148 substitution plus 2 or more additional INSTI-resistance
substitutions including L74I/M, E138A/D/K/T, G140A/S, Y143H/R, E157Q,
G163E/K/Q/R/S, or G193E/R.

Important Safety Information:
Contraindication: Co-administration of TIVICAY with dofetilide
(anti-arrhythmic) is contraindicated due to the potential for increased
dofetilide plasma concentrations and the risk for serious and/or
life-threatening events.

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% or fewer
subjects receiving TIVICAY in Phase III clinical trials. Immediately
discontinue TIVICAY and other suspect agents if signs or symptoms of
hypersensitivity reaction develop, (including but not limited to, severe rash
or rash accompanied by fever, general malaise, fatigue, muscle or joint aches,
blisters or peeling of the skin, oral blisters or lesions, conjunctivitis,
facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing).
Monitor clinical status, including liver aminotransferases, and initiate
appropriate therapy. Delay in stopping treatment with TIVICAY or other suspect
agents after the onset of hypersensitivity may result in a life-threatening
reaction. TIVICAY should not be used in patients who have experienced a
hypersensitivity reaction to TIVICAY.

Effects on Serum Liver Biochemistries in Patients with Hepatitis B or C
Coinfection: 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: Redistribution/accumulation of body fat has been observed
in patients receiving antiretroviral therapy.

Immune Reconstitution Syndrome: During the initial phase of treatment, immune
reconstitution syndrome can occur, which may necessitate further evaluation
and treatment. Autoimmune disorders have been reported to occur in the setting
of immune reconstitution; the time to onset is more variable and can occur
many months after initiation of treatment.

Adverse Reactions: The most commonly reported (>2%) 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%) and
headache (2%).

Drug Interactions: Co-administration of TIVICAY with drugs that are strong
inducers of UGT1A1 and/or CYP3A4 may result in reduced plasma concentrations
of dolutegravir and require dose adjustments of TIVICAY.

TIVICAY should be taken 2 hours before or 6 hours after taking
cation-containing antacids or laxatives, sucralfate, oral iron supplements,
oral calcium supplements, or buffered medications.

Consult the full Prescribing Information for TIVICAY for more information on
potentially significant drug interactions, including clinical comments.

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

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

Paediatric Patients: Safety and efficacy of TIVICAY has not been established
in children younger than 12 years old, or weighing <40 kg, or in
INSTI-experienced paediatric patients with documented or clinically suspected
INSTI resistance.

Please visit the following link for the full U.S. prescribing and patient
information: https://www.viivhealthcare.com/media/58599/us_tivicay.pdf

About FLAMINGO (ING114915)
FLAMINGO is an ongoing phase IIIb/IV, randomised, multi-centre, multinational,
open-label non-inferiority(-12% margin) study with a pre-specified test for
superiority, designed to compare the efficacy and safety of dolutegravir to
darunavir regimens in HIV-1 infected, treatment-naive patients. The primary
objective for FLAMINGO is to demonstrate the antiviral activity of a
dolutegravir regimen compared to a darunavir regimen over 48 weeks. As per
study design, trial participants will continue on therapy in order to assess
the tolerability, long-term safety, and antiviral and immunologic activity of
dolutegravir vs darunavir over 96 weeks. Investigators will also evaluate
viral resistance in patients experiencing virologic failure.

About Tivicay^® (dolutegravir)
Tivicay is an integrase inhibitor indicated for use in combination with other
antiretroviral agents for the treatment of HIV-1 in adults and children aged
12 years and older weighing at least 40 kg. 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.

It is available as a small, yellow, 50mg tablet. Importantly, it can be taken
with or without food and at any time of the day.

ViiV Healthcare announced submission of a Marketing Authorisation Application
(MAA) for dolutegravir to the European Medicines Agency (EMA) on 17 December
2012. Regulatory applications are also being evaluated in other markets
worldwide, including Canada, Australia and Brazil. Submission of regulatory
files to support a fixed-dose combination of Tivicay and abacavir/lamivudine
is anticipated in 2013.

Tivicay is the first new treatment delivered by ViiV Healthcare.

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 as a 10% 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 new HIV medicines, as well as
support communities affected by HIV. For more information on the company, its
management, portfolio, pipeline, and commitment, please
visitwww.viivhealthcare.com.

References

1.Feinberg J et al. Once-Daily Dolutegravir (DTG) is Superior to
    Darunavir/Ritonavir (DRV/r) in Antiretroviral‑Naive Adults: 48 Week
    Results from FLAMINGO (ING114915).
    Presentation Number H-1464a, 12 September 2013. Interscience Conference on
    Antimicrobial Agents and Chemotherapy (ICAAC), Denver, Colorado, U.S.A.

ViiV UK/U.S. Media enquiries:   Rebecca Hunt    +44 (0) 20 8380 6275
                                Marc Meachem    +1 919 483 8756
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                                Jeff McLaughlin + 1 215 751 7002
                                Ziba Shamsi     + 44 (0) 20 8047 3289

GlaxoSmithKline 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. Factors that may affect GSK's operations are described under Item
3.D "Risk factors" in the company's Annual Report on Form 20-F for 2012.

SOURCE ViiV Healthcare

Website: http://www.viivhealthcare.com
 
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