* Dolutegravir is the first integrase inhibitor available as a dispersible tablet for children weighing at least 3kg and from four weeks of age[1]
* The positive opinion follows an FDA approval for Tivicay PD in
The positive opinion follows the
The CHMP's positive opinion is based on data from the ongoing P1093[4] and ODYSSEY[5] (PENTA20) studies, which are being conducted in collaboration with international paediatric research networks, IMPAACT and PENTA-ID. Earlier this year, the dispersible-tablet formulation of dolutegravir was approved for use in the US as Tivicay PD (dolutegravir) tablets for oral suspension, in combination with other antiretroviral agents for the treatment of HIV-1 in paediatric patients (treatment-naïve or -experienced but INSTI- naïve) aged at least four weeks and weighing at least 3kg. In addition, the indication for Tivicay (dolutegravir) 50mg film-coated tablets was extended to paediatric HIV patients weighing 20kg and above.[6]
About P1093[5] and ODYSSEY[6]
* P1093 (NCT03016533): a safety, tolerability and dose finding registrational study in paediatric patients aged four weeks to 18 years being conducted by the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) network in the
* ODYSSEY (Penta20) (NCT02259127): a randomised control efficacy trial in first and second- line treatment, in paediatric patients aged fourweeks to 18 years being conducted by the PENTA network in
About voluntary licensing of paediatric dolutegravir
Currently 15 generic manufacturers hold voluntary licences for paediatric formulations of DTG: one direct license and 14 through the
About Tivicay and Tivicay PD
Tivicay and Tivicay PD contain dolutegravir, an integrase strand transfer inhibitor for use in combination with other antiretroviral agents for the treatment of HIV. Integrase inhibitors inhibit HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral deoxyribonucleic acid (DNA) integration which is essential for the HIV replication cycle.
Trademarks are owned by or licensed to the
Important Safety Information (ISI) for TIVICAY (dolutegravir) tablets, for oral use and TIVICAY PD (dolutegravir) tablets for oral suspension
The following ISI is based on the highlights section of the Prescribing Information for Tivicay. These highlights do not include all the information needed to use TIVICAY safely and effectively. See full prescribing information for TIVICAY.
Indications and Usage
TIVICAY and TIVICAY PD are 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 (treatment-naïve or -experienced) and in paediatric patients (treatment-naïve or -experienced but INSTI- naïve) aged at least 4 weeks and weighing at least 3 kg.
TIVICAY is indicated in combination with rilpivirine as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those
Contraindications
* Previous hypersensitivity reaction to dolutegravir.
* Coadministration with dofetilide.
Warnings and Precautions
* Hypersensitivity reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury, have been reported. Discontinue TIVICAY or TIVICAY PD 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.
* Hepatotoxicity has been reported in patients receiving dolutegravir-containing regimens. Patients with underlying hepatitis B or C may be at increased risk for worsening or development of transaminase elevations. Monitoring for hepatotoxicity is recommended.
* Embryo-fetal toxicity may occur when used at the time of conception and in early pregnancy. An alternative treatment to dolutegravir should be considered at the time of conception through the first trimester of pregnancy due to the risk of neural tube defects. Counsel adolescents and adults of childbearing potential to use effective contraception.
* Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy.
* TIVICAY tablets and TIVICAY PD tablets for oral suspension are not interchangeable.
Adverse Reactions
* The most common adverse reactions of moderate to severe intensity and incidence at least 2% (in those receiving TIVICAY in any one adult trial) are insomnia, fatigue, and headache.
Drug Interactions
* Refer to the full prescribing information for important drug interactions with TIVICAY or TIVICAY PD.
* Drugs that are metabolic inducers may decrease the plasma concentrations of dolutegravir.
* TIVICAY or TIVICAY PD should be taken 2 hours before or 6 hours after taking cation-containing antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. When taken with food, TIVICAY and supplements containing calcium or iron can be taken at the same time.
Use in Specific Populations
* Pregnancy: An alternative treatment to dolutegravir should be considered at the time of conception through the first trimester due to the risk of neural tube defects.
* Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission.
* Females and males of reproductive potential: Pregnancy testing and contraception are recommended in adolescents and adults of childbearing potential.
Please see full prescribing information available at: https://www.medicines.org.uk/emc/product/5248/smpc#gref
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About GSK
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Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D "Risk Factors" in the company's Annual Report on Form 20-F for 2019 and as set out in GSK's "Principle risks and uncertainties" section of the Q3 Results and any impacts of the COVID-19 pandemic.
References
[1] https://www.ema.europa.eu/en/medicines/human/summaries-opinion/tivicay
[2] Tivicay (dolutegravir) US Prescribing Information.
[3] UNAIDS. Global HIV & AIDS statistics - 2020 fact sheet. Available at: https://www.unaids.org/en/resources/fact-sheet Last accessed:
[4] Clinicaltrials.gov. (2019). PH3b, DTG Study in HIV-1 Subjects Completing IMPAACT Study P1093. Available at: https://clinicaltrials.gov/ct2/show/NCT03016533 Last accessed:
[5] Clinicaltrials.gov. (2019). A Randomised Trial of Dolutegravir (DTG)-Based Antiretroviral Therapy vs. Standard of Care (SOC) in Children With HIV Infection Starting First-line or Switching to Second-line. Available at: https://clinicaltrials.gov/ct2/show/NCT02259127?term=PENTA20&draw=2&rank=1 Last accessed:
[6] Tivicay (dolutegravir) US Prescribing Information. Updated in
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