The US Food and Drug Administration (FDA) has approved ViiV Healthcare's 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.
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.
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.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.
“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.
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.
ViiV Healthcare is a global specialist HIV company established in November 2009 by GlaxoSmithKline and Pfizer dedicated to delivering advances in treatment and care for people living with HIV.