ViiV Healthcare Announces FDA Approval to Lower the Weight Limit for dolutegravir in Children and Adolescents Living With HIV

London (ots/PRNewswire) -

Reduction of weight limit to at least 30kg means more children
and adolescents will be eligible for dolutegravir

ViiV Healthcare today announced that the US Food and Drug
Administration (FDA) has approved a supplemental New Drug Application
(sNDA) for dolutegravir 10mg and 25mg oral tablets, reducing the
weight limit from at least 40kg to at least 30kg, in ages 6 to less
than 12 years old, for the treatment of HIV-1 in children and
adolescents.[1] Dolutegravir, in line with the current label, will be
available for use in two paediatric populations: paediatric patients
weighing at least 30kg living with HIV-1 who are treatment naïve (not
previously treated) and who are treatment experienced (previously
treated), as long as they have not taken an integrase inhibitor.[1]

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

This approval is based on 24-week data from the Phase I/II
multi-centre, open-label P1093 study conducted in collaboration with
the International Maternal Pediatric Adolescent AIDS Clinical Trial
(IMPAACT) Network. IMPAACT P1093 is an ongoing pharmacokinetic (PK),
safety and efficacy study of dolutegravir plus optimised background
regimen (OBR) in children and adolescents infected with HIV-1 in age
defined cohorts.[1]

Results from the study show that treatment with dolutegravir plus
OBR was generally well tolerated and provided efficacy through to
week 24 in HIV-1 infected children and adolescents from 6 to 12 years
of age weighing at least 30kg.[1] The adverse event (AE) profile in
the study was similar to that for adults.[1] Grade 2 AEs reported by
more than one patient were decreased neutrophil count (n = 3) and
diarrhoea (n = 2).[1] There were no Grade 3 or 4 drug-related AEs
reported, and no AEs led to discontinuation.[1]

"From day one children and adolescents have been, and remain, a
key focus in our drive to improve outcomes for people living with
HIV," said John C. Pottage, Jr., MD, Chief Scientific and Medical
Officer, ViiV Healthcare. "Through our research and development
efforts, corporate social responsibility programmes, partnerships and
access initiatives, we have made a difference for younger
populations. This approval by the FDA provides more children and
adolescents the option to be treated with dolutegravir in the US, and
supports the global UNAIDS paediatric treatment target."

According to UNAIDS, there were 3.2 million children living with
HIV in 2013, and 2.1 million adolescents living with HIV in 2012,
most of whom live in sub-Saharan Africa.[2],[3] Children and younger
adolescents have a limited number of treatment options available to
meet their particular needs, with many antiretroviral therapies not
approved for use in these populations.[4]

In 2014, ViiV Healthcare granted a voluntary licence to the
Medicines Patent Pool (MPP) and Aurobindo Pharma to allow the generic
manufacture of paediatric formulations of dolutegravir without paying
a royalty in 121 countries where most (99%) children with HIV live.
Under the terms of these agreements, Aurobindo Pharma and generics
companies sub-licensed by the MPP are permitted to manufacture the
new 10mg and 25mg formulations of dolutegravir, subject to local
regulatory approvals. This means that dolutegravir may be made
available to children and adolescents weighing at least 30kg in low
income, least developed, sub-Saharan African and middle income
countries in the future, subject to local regulatory approvals.

ViiV Healthcare is committed to further investigating the
potential of dolutegravir in younger age-groups. The ongoing P1093
study is continuing the evaluation of dolutegravir in paediatric
populations down to four weeks of age, weighing at least 3kg.[5]

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. There is no cure for HIV, but effective
treatment can control the virus so that people with HIV can enjoy
healthy and productive lives.

About the P1093 IMPAACT study

P1093 is a Phase I/II, multi-center, open-label, non-comparative
intensive pharmacokinetic and safety study of dolutegravir in
combination regimens in HIV-1 infected infants, children and
adolescents.[5] The primary objectives of the study are to select a
dolutegravir dose for chronic dosing; to determine the safety and
tolerability of the dose, to evaluate the steady-state
pharmacokinetics of dolutegravir in combination with other
antiretrovirals and to determine the dose of dolutegravir that
achieves a targeted AUC24 (primary PK endpoint) and C24h (secondary
PK endpoint) in children and adolescents.[5]

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.

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

Important Information about Tivicay® (dolutegravir)

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 paediatric patients
weighing at least 30kg.

Use of Tivicay in INSTI-experienced patients should be guided by
the number and type of baseline INSTI substitutions. The efficacy of
Tivicay 50mg 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.

Contraindications: Tivicay is contraindicated (1) in patients with
previous hypersensitivity reaction to dolutegravir, and (2) in
patients 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 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: Co-administration 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 Category B: 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.

Paediatric Patients: Safety and efficacy of Tivicay have not been
established in paediatric patients weighing less than 30kg or in any
paediatric patients who are INSTI-experienced.

Full US Prescribing Information for Tivicay is available at: https
://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescri
bing_Information/Tivicay/pdf/TIVICAY-PI-PIL.PDF

About the Medicines Patent Pool

The Medicines Patent Pool (MPP) is a United Nations-backed public
health organisation working to increase access to HIV, viral
hepatitis C and tuberculosis treatments in low- and middle-income
countries. Through its innovative business model, the MPP partners
with industry, civil society, international organisations, patient
groups and other stakeholders to prioritise, forecast and license
needed medicines and pool intellectual property to encourage generic
manufacture and the development of new formulations. To date, the MPP
has signed agreements with six patent holders for twelve HIV
antiretrovirals and for one hepatitis C direct-acting antiviral. Its
generic partners have distributed more than three billion doses of
low-cost medicines to 117 countries. The MPP was founded and remains
fully funded by UNITAID.

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 (TYO: 4507) 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

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1. Tivicay® (dolutegravir) US prescribing information. Available
at: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/e
n/Prescribing_Information/Tivicay/pdf/TIVICAY-PI-PIL.PDF Last
accessed June 2016

2. UNAIDS. The Gap Report. 2014. Available at http://www.unaids.or
g/sites/default/files/media_asset/UNAIDS_Gap_report_en.pdf. Last
accessed June 2016

3. UNAIDS. Report on the global AIDS epidemic 2013. Available at:
http://www.unaids.org/sites/default/files/media_asset/UNAIDS_Global_R
eport_2013_en_1.pdf. Last accessed June 2016

4. UNAIDS. 90-90-90. An ambitious treatment target to help end the
AIDS epidemic. Available at: http://www.unaids.org/sites/default/file
s/media_asset/90-90-90_en_0.pdf. Last accessed: June 2016

5. IMPAACT P1093 Study Protocol Final Version 4.0 13 April 2016.
Available at: http://impaactnetwork.org/studies/P1093.asp. Last
accessed June 2016

ots Originaltext: ViiV Healthcare
Im Internet recherchierbar: http://www.presseportal.de

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