LONDON, Oct. 22, 2013 /PRNewswire/ -- ViiV Healthcare today announced the submission of a regulatory application in the United States for its investigational single-tablet regimen (STR) combining dolutegravir, abacavir and lamivudine for the treatment of people living with HIV-1. This New Drug Application (NDA) follows the approval of dolutegravir by the US Food and Drug Administration (FDA) in August 2013 under the brand name Tivicay®, approved for use in combination with other antiretroviral agents for the treatment of HIV-1 in adults and children aged 12 years and older weighing at least 40 kg (approx. 88 lbs).
"People living with HIV and their doctors seek to use appropriate treatment options for the individual, while also trying to minimise the number of pills required for effective and acceptable antiretroviral treatment," said Dr John Pottage, Chief Medical Officer, ViiV Healthcare. "This submission aims to make a complete Tivicay-based regimen available for the first time in a single once-daily pill."
In Europe, a Marketing Authorisation Application (MAA) for this single-tablet regimen will be submitted in the near future. The review of the MAA for dolutegravir (DTG), submitted in Europe in December 2012, is in progress with the European Medicines Agency (EMA). A combination tablet containing abacavir (ABC) and lamivudine (3TC) is approved and available in the US under the brand name Epzicom® (abacavir sulfate 600 mg + lamivudine 300 mg) and in the EU under the brand name Kivexa®.
The investigational single-tablet combination of DTG/ABC/3TC has sometimes been referred to as "Trii". The submission announced today is based on data from one pivotal Phase III study of DTG1, supported by three other Phase III/IIIb studies2-4, which evaluated the safety and efficacy of this regimen. It additionally includes pivotal data evaluating the bioequivalence of DTG/ABC/3TC when taken as a single-tablet regimen compared to the administration of DTG with ABC/3TC as separate components5. A further 48-week Phase IIIb/IV study of this single-tablet regimen in treatment-naive HIV-positive women (the ARIA study) is ongoing6.Important Information About Tivicay® (dolutegravir)Indication 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 children aged 12 years and older and weighing at least 40 kg. The following should be considered prior to initiating TIVICAY: poor virologic response was observed in subjects treated with TIVICAY 50 mg twice daily with an INSTI-resistance Q148 substitution plus 2 or more additional INSTI-resistance substitutions including L74I/M, E138A/D/K/T, G140A/S, Y143H/R, E157Q, G163E/K/Q/R/S, or G193E/R.
Important Safety Information:Contraindication: Co-administration of TIVICAY with dofetilide (anti-arrhythmic) is contraindicated due to the potential for increased dofetilide plasma concentrations and the risk for serious and/or life-threatening events.
Hypersensitivity Reactions: Hypersensitivity reactions have been reported and were characterised by rash, constitutional findings, and sometimes organ dysfunction, including liver injury. The events were reported in 1% or fewer subjects receiving TIVICAY in Phase III clinical trials. Immediately discontinue TIVICAY and other suspect agents if signs or symptoms of hypersensitivity reaction develop, (including but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters or peeling of the skin, oral blisters or lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing). Monitor clinical status, including liver aminotransferases, and initiate appropriate therapy. Delay in stopping treatment with TIVICAY or other suspect agents after the onset of hypersensitivity may result in a life-threatening reaction. TIVICAY should not be used in patients who have experienced a hypersensitivity reaction to TIVICAY.
Effects on Serum Liver Biochemistries in Patients with Hepatitis B or C Coinfection: 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: Redistribution/accumulation of body fat has been observed in patients receiving antiretroviral therapy.
Immune Reconstitution Syndrome: During the initial phase of treatment, immune reconstitution syndrome can occur, which may necessitate further evaluation and treatment. Autoimmune disorders have been reported to occur in the setting of immune reconstitution; the time to onset is more variable and can occur many months after initiation of treatment.
Adverse Reactions: The most commonly reported (greater than or equal to 2%) adverse reactions of moderate to severe intensity in treatment-naive adult subjects in any one trial receiving TIVICAY in a combination regimen were insomnia (3%) and headache (2%).
Drug Interactions: Co-administration of TIVICAY with drugs that are strong inducers of UGT1A1 and/or CYP3A4 may result in reduced plasma concentrations of dolutegravir and require dose adjustments of TIVICAY.
TIVICAY should be taken 2 hours before or 6 hours after taking cation-containing antacids or laxatives, sucralfate, oral iron supplements, oral calcium supplements, or buffered medications.
Pregnancy: 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.
Breastfeeding: 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 has not been established in children younger than 12 years old, or weighing <40 kg, or in INSTI-experienced paediatric patients with documented or clinically suspected INSTI resistance.
Important Information About EPZICOM® (ABC+3TC) INDICATION AND USAGE
IMPORTANT SAFETY INFORMATION FOR EPZICOM Hypersensitivity Reactions
Coinfection with Hepatitis B or HCV
Impaired Hepatic Function
Immune Reconstitution Syndrome
Impaired Renal Function
Use With Other Abacavir-, Lamivudine- and/or Emtricitabine-Containing Products
About ViiV HealthcareViiV 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 joined as a 10% shareholder 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.
Prescribing information for TIVICAY is available online at:
https://www.viivhealthcare.com/media/58599/us_tivicay.pdfPrescribing information for EPZICOM is available online at:
ViiV UK/U.S. Media enquiries:
+44 (0) 20 8380 6275Marc Meachem
+1 919 483 8756GSK Global Media enquiries:
+44 (0) 20 8047 5502Melinda Stubbee
+1 919 483 2510GSK Analyst/Investor enquiries:
+44 (0) 20 8047 2248Tom Curry
+ 1 215 751 5419Gary Davies
+ 44 (0) 20 8047 5503James Dodwell
+ 44 (0) 20 8047 2406Jeff McLaughlin
+ 1 215 751 7002Ziba Shamsi
+ 44 (0) 20 8047 3289GlaxoSmithKline 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. Factors that may affect GSK's operations are described under Item 3.D "Risk factors" in the company's Annual Report on Form 20-F for 2012.
|SOURCE ViiV Healthcare|
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