SECURITIES AND EXCHANGE COMMISSION
Washington D.C. 20549
Report of Foreign Issuer
Pursuant to Rule 13a-16 or 15d-16 of
the Securities Exchange Act of 1934
period ending 26 April 2019
980 Great West Road, Brentford, Middlesex, TW8 9GS
of principal executive offices)
by check mark whether the registrant files or
file annual reports under cover Form 20-F or Form
20-F x Form 40-F
by check mark whether the registrant by furnishing the
contained in this Form is also thereby furnishing the
to the Commission pursuant to Rule 12g3-2(b) under the
Exchange Act of 1934.
Issued: 26 April 2019,
London UK - LSE Announcement
ViiV Healthcare announces CHMP
Positive Opinion for Dovato®
(dolutegravir/lamivudine) as a
once-daily, single-pill, two-drug regimen for the treatment of HIV
Recommendation based on landmark GEMINI 1 & 2 studies which
demonstrated non-inferior efficacy of dolutegravir + lamivudine
compared to a traditional dolutegravir-based, three-drug regimen,
in HIV-1 infected, treatment-naïve adults
London, UK, 26 April 2019 - ViiV Healthcare, the global
specialist HIV company, majority owned by GlaxoSmithKline, with
Pfizer Inc. and Shionogi Limited as shareholders, today announced
that the Committee for Medicinal Products for Human Use (CHMP) of
the European Medicines Agency (EMA) has issued a Positive Opinion
recommending marketing authorisation for Dovato, for the treatment
of HIV-1 infection in adults and adolescents above 12 years of age
weighing at least 40 kg, with no known or suspected resistance to
the integrase inhibitor class, or lamivudine.
John C. Pottage, Jr, M.D. Chief Scientific Medical Officer, ViiV
in HIV treatment mean that people living with HIV are living
longer, and are taking daily medication over a longer period of
time. With our portfolio of two-drug regimens, with dolutegravir at
the core, we are establishing a new way of treating HIV which
challenges the three-drug regimen standard of care. This means that
people living with HIV may take fewer drugs while having the same
efficacy outcomes. Today's CHMP Positive Opinion for Dovato is an
important step towards providing treatment-naïve people living
with HIV in Europe the first once-daily, single-pill, complete
2-drug regimen for the treatment of HIV."
Marketing Authorisation Application for the once-daily,
single-pill, 2-drug regimen of Dovato is supported by data from the
landmark global GEMINI 1 & 2 studies that included more than
1,400 HIV-1 infected adults. In these studies, dolutegravir +
lamivudine demonstrated non-inferior efficacy based on plasma HIV-1
RNA <50 copies per millilitre (c/mL), a standard measure of HIV
control, at Week 48 when compared to a three-drug regimen of
dolutegravir and two nucleoside reverse transcriptase inhibitors
(NRTIs), tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), in
treatment-naïve, HIV-1 infected adults. The safety results for
dolutegravir + lamivudine seen in GEMINI 1 & 2 were consistent
with the product labelling for dolutegravir and lamivudine. No
patient who experienced virologic failure in either treatment arm
developed treatment-emergent resistance.
Opinion is one of the final steps before a marketing authorisation
decision is made by the European Commission (EC). A final EC
decision is anticipated within the coming months. Dovato has been
approved by the US Food and Drug Administration and further
regulatory applications have been submitted worldwide.
Notes to editors
About dolutegravir and lamivudine
is an integrase inhibitor (INI) 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.
Dolutegravir is approved in over 100 countries across North
America, Europe, Asia, Australia, Africa and Latin
commonly known as 3TC, 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
are owned by or licensed to the ViiV Healthcare group of
IMPORTANT SAFETY INFORMATION
Safety Information for Tivicay® (dolutegravir)
50 mg tablets and Epivir (lamivudine) 300 mg tablets in the
following Important Safety Information is based on a summary of the
Summary of Product Characteristics for both Tivicay and Epivir.
Please consult the full Summary of Product Characteristics for the
individual products for all the safety information.
For Tivicay and Epivir
HIV-infected patients with severe immune deficiency at the time of
institution of combination antiretroviral therapy (CART), an
inflammatory reaction to asymptomatic or residual opportunistic
pathogens may arise and cause serious clinical conditions, or
aggravation of symptoms. Typically, such reactions have been
observed within the first few weeks or months of initiation of
CART. Relevant examples are cytomegalovirus retinitis, generalised
and/or focal mycobacterial infections, and Pneumocystis jirovecii
pneumonia. Any inflammatory symptoms should be evaluated and
treatment instituted when necessary. Autoimmune disorders (such as
Graves' disease) have also been reported to occur in the setting of
immune reconstitution, however, the reported time to onset is more
variable and these events can occur many months after initiation of
effective viral suppression with antiretroviral therapy has been
proven to substantially reduce the risk of sexual transmission, a
residual risk cannot be excluded. Precautions to prevent
transmission should be taken in accordance with national
should be advised that dolutegravir, lamivudine or any other
antiretroviral therapy does not cure HIV infection and that they
may still develop opportunistic infections and other complications
of HIV infection. Therefore, patients should remain under close
clinical observation by physicians experienced in the treatment of
these associated HIV diseases.
Tivicay 50 mg tablets
is contraindicated in patients with hypersensitivity to the active
substance or to any of the excipients any of the
should not be co-administration with dofetilide.
reactions have been reported with dolutegravir, and were
characterized by rash, constitutional findings, and sometimes,
organ dysfunction, including severe liver reactions. Dolutegravir
and other suspect medicinal products should be discontinued
immediately if signs or symptoms of hypersensitivity reactions
develop (including, but not limited to, severe rash or rash
accompanied by raised liver enzymes, fever, general malaise,
fatigue, muscle or joint aches, blisters, oral lesions,
conjunctivitis, facial oedema, eosinophilia, angioedema). Clinical
status including liver aminotransferases and bilirubin should be
monitored. Delay in stopping treatment with dolutegravir or other
suspect active substances after the onset of hypersensitivity may
result in a life-threatening allergic reaction.
decision to use dolutegravir in the presence of integrase class
resistance should take into account that the activity of
dolutegravir is considerably compromised for viral strains
harbouring Q148+≥2 secondary mutations from G140A/C/S,
E138A/K/T, L74I (see section 5.1). To what extent dolutegravir
provides added efficacy in the presence of such integrase class
resistance is uncertain.
biochemistry elevations consistent with immune reconstitution
syndrome were observed in some hepatitis B and/or C co-infected
patients at the start of dolutegravir therapy. Monitoring of liver
biochemistries is recommended in patients with hepatitis B and/or C
co-infection. Particular diligence should be applied in initiating
or maintaining effective hepatitis B therapy (referring to
treatment guidelines) when starting dolutegravir -based therapy in
hepatitis B co-infected patients.
that decrease dolutegravir exposure should be avoided in the
presence of integrase class resistance. This includes
co-administration with medicinal products that reduce dolutegravir
exposure (e.g. magnesium/ aluminium-containing antacid, iron and
calcium supplements, multivitamins and inducing agents, etravirine
(without boosted protease inhibitors), tipranavir/ritonavir,
rifampicin, St. John's wort and certain anti-epileptic medicinal
increased metformin concentrations. A dose adjustment of metformin
should be considered when starting and stopping co-administration
of dolutegravir with metformin, to maintain glycaemic control.
Metformin is eliminated renally and, therefore, it is of importance
to monitor renal function when co-treated with dolutegravir. This
combination may increase the risk for lactic acidosis in patients
with moderate renal impairment (stage 3a creatinine clearance
[CrCl] 45- 59 mL/min) and a cautious approach is recommended.
Reduction of the metformin dose should be highly
factors that decrease dolutegravir exposure should be avoided in
the presence of integrase class resistance.
clinical development programme the most severe adverse reaction,
seen in an individual patient, was a hypersensitivity reaction that
included rash and severe liver effects. The most commonly seen
treatment emergent adverse reactions were nausea (13%), diarrhoea
(18%) and headache (13%).
Epivir 300 mg tablets
(lamivudine) is contraindicated in patients with hypersensitivity
to the active substance or to any of the excipients.
is not recommended for use as monotherapy.
impairment: In patients with moderate to severe renal impairment,
the terminal plasma half-life of lamivudine is increased due to
decreased clearance, therefore the dose should be
Cases of pancreatitis have occurred rarely. However, it is not
clear whether these cases were due to the antiretroviral treatment
or to the underlying HIV disease. Treatment with lamivudine should
be stopped immediately if clinical signs, symptoms or laboratory
abnormalities suggestive of pancreatitis occur.
and metabolic parameters: An increase in weight and in levels of
blood lipids and glucose may occur during antiretroviral therapy.
Such changes may in part be linked to disease control and life
style. For lipids, there is in some cases evidence for a treatment
effect, while for weight gain there is no strong evidence relating
this to any particular treatment. For monitoring of blood lipids
and glucose reference is made to established HIV treatment
guidelines. Lipid disorders should be managed as clinically
disease: If lamivudine is being used concomitantly for the
treatment of HIV and HBV, additional information relating to the
use of lamivudine in the treatment of hepatitis B infection is
available in the Zeffix SPC.
with chronic hepatitis B or C and treated with combination
antiretroviral therapy are at an increased risk of severe and
potentially fatal hepatic adverse events. In case of concomitant
antiviral therapy for hepatitis B or C, please refer also to the
relevant product information for these medicinal
lamivudine is discontinued in patients co-infected with hepatitis B
virus, periodic monitoring of liver function tests and markers of
HBV replication is recommended, as withdrawal of lamivudine may
result in an acute exacerbation of hepatitis.
with pre-existing liver dysfunction, including chronic active
hepatitis, have an increased frequency of liver function
abnormalities during combination antiretroviral therapy, and should
be monitored according to standard practice. If there is evidence
of worsening liver disease in such patients, interruption or
discontinuation of treatment must be considered.
Interactions: Lamivudine should not be taken with any other
medicinal products containing lamivudine or medicinal products
containing emtricitabine. The combination of lamivudine with
cladribine is not-recommended.
following common adverse reactions have been reported during
therapy for HIV disease with lamivudine. Common: (≥1/100 to
<1/10); Headache, insomnia, cough, nasal symptoms, nausea,
vomiting, abdominal pain or cramps, diarrhoea, rash, alopecia,
arthralgia, muscle disorders, fatigue, malaise, fever.
refer to the full European Summary of Product Characteristics for
lamivudine for full prescribing
information, including contraindications, special warnings and
precautions for use.
About ViiV Healthcare
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 aims 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.
more information on the company, its management, portfolio,
pipeline, and commitment, please visit
a science-led global healthcare company with a special purpose: to
help people do more, feel better, live longer. For further
information please visit www.gsk.com.
Healthcare media enquiries:
Global media enquiries:
Cautionary statement regarding forward-looking
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 2018.
in England & Wales:
Great West Road
European Medicines Agency.
Press releases. Available at
Last accessed April 2019
Cahn J, Sierra Madero J,
Arribas J, et al. Non-inferior efficacy of dolutegravir (DTG) plus
lamivudine (3TC) versus DTG plus tenofovir/emtricitabine (TDF/FTC)
fixed-dose combination in antiretroviral treatment-naïve
adults with HIV-1 infection - 48-week results from the GEMINI
studies. AIDS 2018.
(dolutegravir/lamivudine) Prescribing Information. U.S. Approval 8
European Summary of Product Characteristics. Available at:
epar -product-information_en.pdf. Last accessed February
European Medicines Agency.
Epivir (lamivudine) European Summary of Product Characteristics.
epar -product-information_en.pdf. Last accessed February
to the requirements of the Securities Exchange Act of 1934, the
registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorised.
Signatory for and on
of GlaxoSmithKline plc