LONDON, Aug. 22, 2014 /PRNewswire/ -- ViiV Healthcare
announced today that the US Food and Drug Administration (FDA) has
approved Triumeq® (abacavir 600mg, dolutegravir 50mg and
lamivudine 300mg) tablets for the treatment of HIV-1
infection.1 Triumeq is ViiV Healthcare's first
dolutegravir-based fixed-dose combination, offering many people
living with HIV the option of a single-pill regimen that combines
the integrase strand transfer inhibitor (INSTI) dolutegravir, with
the nucleoside reverse transcriptase inhibitors (NRTIs) abacavir
and lamivudine.
Triumeq alone is not recommended for use in patients with
current or past history of resistance to any components of Triumeq.
Triumeq alone is not recommended in patients with
resistance-associated integrase substitutions or clinically
suspected INSTI resistance because the dose of dolutegravir in
Triumeq is insufficient in these populations. Before initiating
treatment with abacavir-containing products, screening for the
presence of a genetic marker, the HLA-B*5701 allele, should be
performed in any HIV-infected patient, irrespective of racial
origin. Products containing abacavir should not be used in patients
known to carry the HLA-B*5701 allele.1
Dr Dominique Limet, Chief
Executive Officer, ViiV Healthcare, said: "Today's approval of
Triumeq offers many people living with HIV in the US the first
single-pill regimen containing dolutegravir. ViiV Healthcare is
committed to delivering advances in care and new treatment options
to physicians and people living with HIV. We are proud to announce
this important milestone, marking the second new treatment to be
approved in the US from our pipeline of medicines."
This FDA approval is based primarily upon data from two clinical
trials:
- the Phase III study (SINGLE) of treatment-naive adults,
conducted with dolutegravir and abacavir/lamivudine as separate
pills2,3
- a bioequivalence study of the fixed-dose combination of
abacavir, dolutegravir and lamivudine when taken as a single pill
compared to the administration of dolutegravir and
abacavir/lamivudine as separate pills.4
In the SINGLE study, a non-inferiority trial with a
pre-specified superiority analysis, more patients were undetectable
(HIV-1 RNA <50 copies/mL) in the dolutegravir and
abacavir/lamivudine arm (the separate components of Triumeq) than
in the Atripla®+ (efavirenz, emtricitabine and
tenofovir) arm, the most commonly used single-pill regimen. The
difference was statistically significant and met the pre-specified
test for superiority. The difference was driven by a higher rate of
discontinuation due to adverse events in the Atripla arm.2,
3
- At 96 weeks, 80% of participants on the dolutegravir-based
regimen were virologically suppressed compared to 72% of
participants on Atripla. Grade 2-4 treatment emergent adverse
reactions occurring in 2% or more participants taking the
dolutegavir-based regimen were insomnia (3%), headache (2%) and
fatigue (2%).3
About HIV
HIV stands for the Human Immunodeficiency Virus. Unlike some
other viruses, the human body cannot get rid of HIV, so once
someone has HIV they have it for life.5-7
HIV infects specific cells of the immune system, called CD4
cells or T-cells. Over time, HIV can destroy so many of these cells
that the body cannot fight off infections and disease. When this
happens, HIV infection leads to Acquired Immunodeficiency Syndrome
(AIDS) which is the final stage of HIV infection. There is no cure
for HIV, but with early diagnosis and effective treatment most
people with HIV will not go on to develop AIDS.5-7
An estimated 1.1 million people in the US are living with HIV.
However, only 33 per cent are taking the medication they
need.8
About Triumeq
Triumeq is a fixed-dose combination containing the INSTI
dolutegravir and the 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 and further
infecting cells.
Dolutegravir was approved in the US in August 2013 and in Europe in January
2014 under the brand name Tivicay®. The Committee
for Medicinal Products for Human Use (CHMP) of the European
Medicines Agency (EMA) granted a positive opinion on the Marketing
Authorisation Application (MAA) for Triumeq on 26 June 2014. Regulatory applications are also
being evaluated in other markets worldwide, including Australia, Brazil and Canada.
Tivicay and Triumeq are registered trademarks of the ViiV
Healthcare group of companies.
Important Safety Information (ISI) for Triumeq
(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 labeled safety information for
Triumeq.
BOXED WARNING: RISK OF HYPERSENSITIVITY REACTIONS, LACTIC
ACIDOSIS AND SEVERE HEPATOMEGALY, 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 to 2%) 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 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 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 visit
www.viivhealthcare.com.
References:
- Triumeq US label
- Walmsley SL, Antela A, Clumeck N et al; for the SINGLE
Investigators. Dolutegravir plus abacavir–lamivudine for the
treatment of HIV-1 infection. N Engl J Med.
2013;369(19):1807-1818.
- Walmsley S, Berenguer J, Khuong-Josses M, et al.
Dolutegravir regimen statistically superior to
efavirenz/tenofovir/emtricitabine: 96-week results from the SINGLE
study (ING114467). Poster presented at: 21st Conference on
Retroviruses and Opportunistic Infections; March 3-6, 2014; Boston, MA. Poster 543.
- Weller S, Chen S, Borland J et al. Bioequivalence of a
Dolutegravir, Abacavir and Lamivudine Fixed-Dose Combination Tablet
and the Effect of Food. JAIDS. 2014 May doi:
10.1097/QAI.0000000000000193.http://journals.lww.com/jaids/Abstract/publishahead/Bioequivalence_of_a_Dolutegravir,_Abacavir_and.97920.aspx.
- Centers for Disease Control and Prevention. HIV Basics.
http://www.cdc.gov/hiv/basics/index.html. Accessed July 28, 2014.
- NHS Choices, HIV & AIDS Overview.
http://www.nhs.uk/conditions/HIV/Pages/Introduction.aspx. Accessed
July 28, 2014.
- Centers for Disease Control and Prevention. CDC Fact Sheet. HIV
in the United States: The Stages
of Care. http://www.cdc.gov/hiv/pdf/research_mmp_StagesofCare.pdf.
Accessed July 28, 2014.
- Centers for Disease Control and Prevention. Today's HIV/AIDS
Epidemic.
http://www.cdc.gov/nchhstp/newsroom/docs/HIVFactSheets/TodaysEpidemic-508.pdf.
Accessed July 28, 2014.
+Atripla is a registered trademark of Bristol-Meyers
Squibb and Gilead Sciences, LLC.
ViiV UK/US Media
enquiries:
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+44 7920 567
707
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2510
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Shamsi
Kirsty Collins (SRI
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Tom Curry
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Davies
James
Dodwell
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+44 20 8047
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+44 20 8047
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5419
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+44 20 8047
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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 2013.