LONDON, July 25, 2017 /PRNewswire/ --
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.
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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 ≥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 (≥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