LONDON, August 16, 2016 /PRNewswire/ --
ViiV Healthcare today announced the start of a phase III
programme to support regulatory filings for a two-drug regimen of
dolutegravir (Tivicay®) and lamivudine (Epivir®) 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®). 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® is a registered trademark of the ViiV Healthcare group
of companies.
Tivicay® is a registered trademark of the ViiV Healthcare group
of companies.
Truvada® is a registered trademark of Gilead Sciences, Inc.
About Tivicay® (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®) 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® (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® 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 (≥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.
EPIVIR® (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.
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