ViiV Healthcare Announces Superior Efficacy of Dolutegravir Versus Lopinavir/Ritonavir in Second-line HIV Treatment in Resource-limited Settings

PR69451

LONDON, July 25, 2017 /PRNewswire=KYODO JBN/ --

- DAWNING study modified to allow patients the opportunity to receive

dolutegravir-based regimens

ViiV Healthcare, the global specialist HIV company, majority owned by GSK, with

Pfizer Inc. and Shionogi Limited as shareholders, today announced positive

interim results from DAWNING. This is a non-inferiority study conducted to

compare second-line treatment of the protease inhibitor-sparing regimen of

dolutegravir and 2 nucleoside reverse transcriptase inhibitors (NRTIs), with a

current WHO-recommended regimen of lopinavir/ritonavir and 2 NRTIs in

HIV-1-infected adults. Results are being presented at the International AIDS

Society congress in Paris.

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

The study's Independent Data Monitoring Committee (IDMC) noted significant and

clinically-relevant differences between treatment arms in favour of

dolutegravir and recommended that the boosted lopinavir treatment arm be

discontinued. Participants receiving lopinavir/ritonavir were offered the

opportunity to switch to a regimen with dolutegravir as the core agent, if

considered appropriate by the investigator.

The primary endpoint was the proportion of patients with plasma HIV-1 RNA <50

copies per millilitre (c/mL) at week 48. The 24-week interim data showed an 82%

response rate in the dolutegravir arm versus 69% for lopinavir/ritonavir

(p<0.001). Key secondary endpoints include evaluation of the development of

viral resistance and measurements of safety and tolerability. No subjects in

the dolutegravir arm of the study failed treatment with either integrase or

nucleoside resistance. The safety data for dolutegravir at week 24 was

consistent with previous dolutegravir studies. Additional data from DAWNING

will be presented at future medical meetings.

John C Pottage, Jr, MD, Chief Scientific and Medical Officer, ViiV Healthcare,

commented "The initial results from DAWNING are important because they not only

provide information that may help guide second-line treatment decisions in

resource-limited settings, but also reaffirm the position of dolutegravir at

the core of HIV care. We are working with investigators to ensure that

dolutegravir can be provided to patients in the control arm and are looking

forward to sharing the 48-week results, as soon as they will be available."

Notes to editors   

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

For more information on the trials please visit: http://www.clinicaltrials.gov

About the DAWNING study   

DAWNING is a phase IIIb, non-inferiority study conducted to compare a protease

inhibitor-sparing regimen of DTG and 2 NRTIs with a current WHO-recommended

regimen of LPV/RTV + 2 NRTIs in HIV-1 infected patients failing first-line

therapy of a NNRTI + 2 NRTIs (ClinicalTrials.gov: NCT02227238). The IDMC

performed periodic reviews of data to protect the ethical and safety interests

of patients.

Adult patients failing first-line therapy, with HIV-1 RNA &#8805;400

copies(c)/mL, were randomised (1:1, stratified by baseline plasma HIV-1 RNA and

number of fully active background NRTIs) to 52 weeks of open-label treatment

with DTG or LPV/RTV combined with an investigator-selected dual NRTI

background, including at least one fully active NRTI.

TIVICAY (dolutegravir) tablets   

Professional Indication(s) and Important Safety Information   

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 paediatric 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 characterized by rash,

constitutional findings, and sometimes organ dysfunction, including liver

injury. The events were reported in <1% of subjects receiving TIVICAY in phase

III 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 (&#8805;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.

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 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

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.

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 'Principal risks and uncertainties' in the company's Annual Report on

Form 20-F for 2016.

SOURCE: ViiV Healthcare