ViiV HEALTHCARE ANNOUNCES FDA APPROVAL TO LOWER THE WEIGHT LIMIT FOR DOLUTEGRAVIR IN CHILDREN AND ADOLESCENTS LIVING WITH HIV
London, UK, 10 June 2016 –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. 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
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.1Grade 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., 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.
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.
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 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 www.viivhealthcare.com
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 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
 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
 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
 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
 IMPAACT P1093 Study Protocol Final Version 4.0 13 April 2016. Available at: http://impaactnetwork.org/studies/P1093.asp. Last accessed June 2016