LONDON, June 10, 2016 /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/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® (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