ViiV Healthcare files submissions to the FDA and EMA for the first-ever dispersible formulation of dolutegravir (DTG) for children living with HIV

Notes to editors:

About P1093 and ODYSSEY4,5

• P1093 (NCT03016533): investigates the safety, pharmacokinetic, tolerability and antiviral activity of DTG regimens in paediatric patients aged four weeks to 18 years and is being conducted by the IMPAACT network in the U.S., Brazil, Thailand, South Africa, Zimbabwe, and Malawi.
• ODYSSEY (PENTA20) (NCT02259127): is designed to understand how DTG as first- or second-line treatment compares to the current standards of care in paediatric patients aged four weeks to 18 years and is being conducted by the Penta network in Europe, South America, Thailand, Uganda, Zimbabwe, and South Africa. Originally designed to support the World Health Organization (WHO) guideline recommendations by WHO weight bands, this study will now provide data to support this submission. For more information, please visit the study website at: http://odysseytrial.org/

About dolutegravir
Dolutegravir (Tivicay) is an integrase strand transfer inhibitor (INSTI) for use in combination with other antiretroviral (ARV) 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.

Tivicay is a registered trademark of the ViiV Healthcare group of companies. registration status of Tivicay worldwide. Click here for the latest registration status of Tivicay worldwide.

Important Safety Information (ISI) for dolutegravir 10, 25, and 50 mg tablets
The following Important Safety Information is based on the Summary of Product Characteristics (SmPC) for dolutegravir (Tivicay). Please consult the full SmPC for the full safety information.

Indications and Usage
Dolutegravir is a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI) indicated in combination with:

• other ARV agents for the treatment of HIV-1 infection in adults and paediatric patients weighing at least 30 kg
• rilpivirine as a complete regimen for the treatment of HIV-1 infection in adults to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA <50 copies per mL) on a stable ARV regimen for ≥6 months with no history of treatment failure or known substitutions associated with resistance to either ARV agent

Important Safety Information
CONTRAINDICATIONS

• Do not use dolutegravir in patients with previous hypersensitivity reaction to dolutegravir
• Do not use dolutegravir in patients receiving dofetilide

WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions:

• Hypersensitivity reactions have been reported with dolutegravir and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury
• Discontinue dolutegravir immediately if signs or symptoms of hypersensitivity reaction develop, as a delay in stopping treatment may result in a life-threatening reaction. Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated

Hepatotoxicity:

• Hepatic adverse events have been reported, including cases of hepatic toxicity (elevated serum liver biochemistries, hepatitis, and acute liver failure) in patients receiving a dolutegravir containing regimen without pre-existing hepatic disease or other identifiable risk factors
• Patients with underlying hepatitis B or C or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations with use of dolutegravir. 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
• Monitoring for hepatotoxicity is recommended

Embryofetal Toxicity:

• Alternative treatments to dolutegravir should be considered at the time of conception through the first trimester of pregnancy due to the risk of neural tube defects
• Perform pregnancy testing before use of dolutegravir and counsel that consistent use of effective contraception is recommended while using dolutegravir in adolescents and adults of childbearing potential

Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions with concomitant use of dolutegravir and other drugs may result in known or potentially significant drug interactions (see Contraindications or Drug Interactions).

Immune Reconstitution Syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported with the use of dolutegravir.

ADVERSE REACTIONS
The most common adverse reactions (incidence ≥2%, Grades 2-4) in treatment-naïve adults receiving dolutegravir in a combination regimen were insomnia (3%), headache (2%), and fatigue (2%).

DRUG INTERACTIONS

• Coadministration of dolutegravir with drugs that induce or inhibit UGT1A1 and/or CYP3A may affect plasma concentrations 
• Administer dolutegravir 2 hours before or 6 hours after taking antacids, polyvalent cation-containing products or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. Alternatively, oral calcium and iron supplements (including multivitamins containing calcium or iron) can be taken with dolutegravir if co-administered with a meal
• Consult the full Prescribing Information for dolutegravir for more information on potentially significant drug interactions, including clinical comments

USE IN SPECIFIC POPULATIONS

• Pregnancy: There are insufficient human data on the use of dolutegravir during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage. An Antiretroviral Pregnancy Registry has been established. If planning a pregnancy or if pregnancy is confirmed while taking dolutegravir during the first trimester, assess the risks and benefits of continuing dolutegravir versus switching to another ARV regimen. For individuals actively trying to become pregnant, initiation of dolutegravir is not recommended unless there is no suitable alternative
• Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission, developing viral resistance in HIV-positive infants, and adverse reactions in a breastfed infant
• Females and Males of Reproductive Potential: Perform pregnancy testing before initiation of dolutegravir. Advise adolescents and adults of childbearing potential to consistently use effective contraception while taking dolutegravir

Please see accompanying full Product Information for more details.
Full U.S. prescribing information including is available at: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Informatio n/Tivicay/pdf/TIVICAY-PI-PIL.PDF

For the EU Summary of Product Characteristics, please visit: https://www.ema.europa.eu/en/documents/product-information/tivicay-epar-productinformation_en.pdf

About The International Maternal Paediatric Adolescent AIDS Clinical Trials (IMPAACT) Network
The International Maternal Paediatric Adolescent AIDS Clinical Trials (IMPAACT) Network is a global collaboration of investigators, institutions, community representatives and other partners organised for the purpose of evaluating interventions to treat and prevent HIV infection and its consequences in infants, children, adolescents and pregnant/postpartum women through the conduct of high-quality clinical trials.

The IMPAACT Network's research agenda includes evaluation of: new and existing anti-HIV drugs and formulations; novel approaches for addressing tuberculosis in HIV-infected or at-risk populations; biomedical/behavioural interventions to prevent mother-to-child HIV transmission; immunogenicity, safety and efficacy of high priority vaccines; potential for HIV cure through therapeutic interventions; and methods to prevent and manage complications and comorbidities of HIV infection and its treatment.

For more information on IMPAACT visit: https://impaactnetwork.org/

About Penta
Penta is a global independent scientific network dedicated to research in child health. Starting out from its work in HIV, today Penta’s portfolio includes investigation into other infectious diseases affecting children, as well as infrastructure development initiatives and training programmes. Since 2012, Penta has sponsored 35 clinical trials, with more than 50,000 women and children enrolled into its studies. The work of Penta is supported by a network of 110 clinical sites in 31 countries across the world whose expertise are leveraged to transform the prevention and treatment of infection in children.

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 and for people who are at risk of becoming infected with HIV. Shionogi 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 innovative medicines for HIV treatment and prevention, 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

About GSK
GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit www.gsk.com.

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 'Principal risks and uncertainties' in the company's Annual Report on Form 20-F for 2018.