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

PR64748

LONDON, Jun. 10 /PRNewswire=KYODO JBN / --

    - 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 naive (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(R) (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(R) (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 (greater than or equal to2%)

adverse reactions of moderate to severe intensity in treatment-naive 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/Prescribing_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

    ------------------------------------------------------

    1. Tivicay(R) (dolutegravir) US prescribing information. Available at:

https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Tivicay/pdf/TIVICAY-PI-PIL.PDF

Last accessed June 2016

    2. UNAIDS. The Gap Report. 2014. Available at

http://www.unaids.org/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_Report_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/files/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

SOURCE: ViiV Healthcare