Welcome!

News Feed Item

ViiV Healthcare's new HIV medicine Tivicay™ (dolutegravir) is approved in Europe

LONDON, Jan. 21, 2014 /PRNewswire/ -- ViiV Healthcare today announced that the European Commission has approved Tivicay (dolutegravir), an integrase inhibitor, for use in combination with other anti-retroviral medicinal products for the treatment of HIV infected adults and adolescents above 12 years of age.

The Tivicay clinical development programme was comprehensive in its breadth, including people living with HIV who were new to treatment (naive), as well as those who had already  been treated with other HIV medicines (experienced) and those who were infected with a virus that had developed resistance to previously available integrase inhibitors. The submission supporting today's approval included data from four pivotal Phase III clinical trials in which 2,557 adults received treatment with Tivicay or a comparator1-4. The submission also included data from a fifth study in children aged 12 years and older5.

"Today's approval of Tivicay is an important advance, opening the door to new treatment combinations for people living with HIV in Europe. Tivicay's clinical development programme was only possible through partnerships with the people living with HIV and healthcare professionals who participated in it, and we aim to move forward together with them based on an absolute commitment to the HIV/AIDS global response," said Dr Dominique Limet, Chief Executive Officer, ViiV Healthcare.

Today's approval of Tivicay is the European regulatory authorisation to market the medicine in each member state of the European Union. Tivicay will become available in each country as pricing and reimbursement processes are completed, with availability in some of the first countries anticipated in the immediate future.

The efficacy of Tivicay – as a 'third agent' – was statistically superior to its comparator in two pivotal Phase III studies1,2 and non-inferior in a third comparator study3. In clinical trials1-4, Tivicay had low rates of discontinuation due to adverse events (1-3%) in both treatment-naive and treatment-experienced patients.

"HIV treatment is not a question of 'one-size fits all' – especially now that treatment is something that patients will live with for many years," said Dr John Pottage, Chief Medical Officer, ViiV Healthcare. "We continue to find measurable clinical differences among the treatments now available for use in combination therapy to combat HIV. Using the clinical data for Tivicay, doctors and people living with HIV can fully consider the effectiveness against the virus and the side effect profile that Tivicay may bring."

The safety profile is based on pooled data from Phase IIb and Phase III clinical studies in 980 previously untreated patients, 357 previously treated patients unexposed to integrase inhibitors and 234 patients with prior treatment failure that included an integrase inhibitor (including integrase class resistance).  The most commonly seen treatment emergent adverse reactions were nausea (15%), diarrhoea (16%) and headache (14%). The most severe adverse reaction, seen in an individual patient, was a hypersensitivity reaction that included rash and severe liver effects.

Tivicay inhibits an enzyme used by the HIV virus during its replication cycle, known as integrase. By binding to the site where integrase acts, it blocks the "strand transfer" step of the HIV replication process – stopping the viral DNA from forming a new virus. The recommended dose of Tivicay for most patients is one 50 mg tablet once daily. For patients with documented or clinically suspected resistance to the integrase class, or when co-administered with certain medicines, the recommended dose of Tivicay is 50 mg twice daily. Please refer to the full European Summary of Product Characteristics for full prescribing information, including contraindications, special warnings and precautions for use6.

Important Safety Information for Tivicay in the European Union:

The decision to use dolutegravir in the presence of integrase class resistance should take into account that the activity of dolutegravir is considerably compromised for viral strains harbouring Q148 plus two or more secondary mutations from G140A/C/S, E138A/K/T, L74I. To what extent dolutegravir provides added efficacy in the presence of such integrase class resistance is uncertain.

Co-administration of dolutegravir with dofetilide is contraindicated.

Hypersensitivity reactions have been reported with dolutegravir, and were characterised by rash, constitutional findings, and sometimes, organ dysfunction, including severe liver reactions. Dolutegravir and other suspect agents should be discontinued immediately if signs or symptoms of hypersensitivity reactions develop.

In HIV-infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms. Typically, such reactions have been observed within the first few weeks or months of initiation of CART.

Liver biochemistry elevations consistent with immune reconstitution syndrome were observed in some hepatitis B and/or C co-infected patients at the start of dolutegravir therapy. 

Patients should be advised that dolutegravir or any other antiretroviral therapy does not cure HIV infection and that they may still develop opportunistic infections and other complications of HIV infection.

Factors that decrease dolutegravir exposure should be avoided in the presence of integrase class resistance. This includes co-administration with medicinal products that reduce dolutegravir exposure.  Also, metformin concentrations may be increased by dolutegravir. 

Cases of osteonecrosis have been reported in patients with advanced HIV-disease and/or long-term exposure to CART. Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.

Please refer to the full European Summary of Product Characteristics for full prescribing information, including contraindications, special warnings and precautions for use6.

About the Phase III Clinical Trial Programme

SINGLE1 was a study evaluating once-daily Tivicay plus abacavir/lamivudine versus the single tablet regimen Atripla®* in 833 HIV-infected, treatment-naive patients. Virologic suppression among patients treated with a regimen comprising Tivicay, abacavir (ABC) and lamivudine (3TC) was 88% (n=414), which was statistically superior to the result for those treated with efavirenz (EFV), tenofovir (TDF) and emtricitabine (FTC) (81% at week 48, n=419, p=0.003 – a difference driven primarily by treatment discontinuations due to adverse events). 2% of subjects on the Tivicay-based regimen discontinued due to adverse events versus 10% of those receiving the comparator (EFV/TDF/FTC - Atripla®*). For Tivicay, treatment-emergent adverse drug reactions of at least moderate intensity (Grades 2 to 4) and >2% frequency were insomnia (3%) and headache (2%), and for Atripla® were rash (6%), dizziness (5%), nausea (3%), and insomnia, abnormal dreams, headache, diarrhoea, and vertigo (2%).

No treatment-emergent genotypic resistance that resulted in reduced susceptibility to either Tivicay or the background regimen was seen in the arm containing Tivicay in SINGLE at week 48.

SAILING2 was a study evaluating once-daily Tivicay versus twice-daily raltegravir in 719 patients with HIV who were failing on current therapy, but had not been treated with an integrase inhibitor, in each case in combination with an investigator-selected background regimen consisting of up to two agents, including at least one fully active agent. Virologic suppression among those treated with a combination containing Tivicay (71%, n=354) was statistically superior to the result for those treated with a combination containing raltegravir (64%, n=361), at week 48 (p=0.03). Overall, the tolerability of Tivicay was similar to that of raltegravir, with adverse events leading to withdrawal in 3% of patients on the Tivicay regimen versus 4% among those taking the raltegravir regimen. There were no treatment-emergent adverse drug reactions of at least moderate intensity (Grades 2 to 4) and >2% frequency in the arm containing Tivicay compared with diarrhoea in 2% of patients in the raltegravir arm.

Viruses from five of 15 subjects with post-baseline resistance data in the arm containing Tivicay had evidence of treatment-emergent genetic changes (integrase substitutions). However, none of these patients had decreases in susceptibility to either Tivicay or raltegravir.

SPRING-23 was a study evaluating once-daily Tivicay versus twice-daily raltegravir in 822 HIV-infected, treatment-naive patients, in each case in combination with a fixed-dose dual-NRTI treatment. 88% of patients treated with a combination containing Tivicay 50 mg once daily (n=411) achieved virologic suppression (HIV-1 RNA <50 copies/mL), compared to 85% of patients in the raltegravir 400 mg twice-daily group (n=411) at 48 weeks, meeting the 10% non-inferiority criteria. The tolerability of Tivicay was similar to that of raltegravir, with adverse events leading to withdrawal in 2% of patients in both arms. There were no treatment-emergent adverse drug reactions of at least moderate intensity (Grades 2 to 4) and >2% frequency in the Tivicay or raltegravir arms.

No treatment-emergent genotypic resistance to Tivicay or the background regimen was seen in the arm containing Tivicay in SPRING-2 at week 48.

VIKING-34 was a study evaluating twice-daily Tivicay in 183 HIV-infected adults currently on medication whose HIV was resistant to multiple classes of HIV medicines, including integrase inhibitors (raltegravir and/or elvitegravir). In the study, mean HIV RNA levels declined by 1.4 log10 c/mL after seven days of treatment with the addition of Tivicay to their background regimen. The proportion of study participants who were subsequently virologically suppressed (HIV-1 RNA <50 c/mL) with Tivicay plus an optimized background regimen was 63% at week 24. However, poor virologic response was observed in subjects treated with Tivicay twice daily with an integrase inhibitor (INI) resistance-associated substitution called Q148 plus two or more additional secondary INI resistance substitutions. The rate of adverse events leading to discontinuation was 3% of subjects at week 24. Treatment-emergent adverse drug reactions in VIKING-3 were generally similar compared with observations with the once-daily, 50-mg dose in Phase III trials of adult patients.

The indication in children aged 12 years and older is based on an evaluation of safety, pharmacokinetics, and efficacy through 24 weeks in a multi-centre, open-label trial in paediatric patients aged 12-<18 years old who had not previously been treated with integrase inhibitors5.

About Tivicay (dolutegravir)

Please refer to local country prescribing information (the European SmPC for those in Europe6). Tivicay® is the first new treatment delivered by ViiV Healthcare. It was approved by the U.S. FDA in August 2013, by Health Canada in October 2013 and regulatory applications are being evaluated in other countries worldwide. It is a human immunodeficiency virus type 1 (HIV-1) integrase inhibitor. 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.

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 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.

References

1    Walmsley S, Antela A, Clumeck N et al. Dolutegravir plus abacavir/lamivudine for the initial treatment of HIV-1 infection.  N Engl J Med 2013;369:1807-18.

2    Cahn P, Pozniak AL, Mingrone H et al. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet 2013;382(9893):700-708.

3    Raffi F, Rachlis A, Stellbrink H-J et al. Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study. Lancet 2013;381(9868):735-743.

4    Eron JJ, Clotet B, Durant J et al. Safety and efficacy of dolutegravir in treatment-experienced subjects with raltegravir-resistant HIV type 1 infection: 24-week results of the VIKING study. J Infect Dis. 2013;207(5):740-748.

5    Hazra R, Viani R, Acosta E et al. Pharmacokinetics, safety and efficacy of dolutegravir (DTG; S/GSK1349572) in HIV-1-positive adolescents: preliminary analysis from IMPAACT P1093. 19th International AIDS Conference (IAC), 2012. Abstract TUAB0203.

6    Tivicay (dolutegravir) Summary of Product Characteristics (SmPC). Available at www.viivhealthcare.com/our-medicines.aspx

*Atripla is a registered trademark of Bristol-Myers Squibb and Gilead Sciences, LLC.

ViiV UK/U.S. Media enquiries:

Rebecca Hunt

+44 (0) 20 8380 6275


Marc Meachem

+1 919 483 8756

GSK Global Media enquiries:

David Daley

+44 (0) 20 8047 5502


Melinda Stubbee

+1 919 483 2510

GSK Analyst/Investor enquiries:

Sally Jackson

+44 20 8047 5543


Kirsty Collins (SRI & CG) 

+44 20 8047 5534


Tom Curry

+ 1 215 751 5419


Gary Davies

+ 44 (0) 20 8047 5503


James Dodwell

+ 44 (0) 20 8047 2406


Jeff McLaughlin

+ 1 215 751 7002


Ziba Shamsi

+ 44 (0) 20 8047 3289


Lucy Singah

+44 (0) 20 8047 2248

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.

 

More Stories By PR Newswire

Copyright © 2007 PR Newswire. All rights reserved. Republication or redistribution of PRNewswire content is expressly prohibited without the prior written consent of PRNewswire. PRNewswire shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.

Latest Stories
What sort of WebRTC based applications can we expect to see over the next year and beyond? One way to predict development trends is to see what sorts of applications startups are building. In his session at @ThingsExpo, Arin Sime, founder of WebRTC.ventures, will discuss the current and likely future trends in WebRTC application development based on real requests for custom applications from real customers, as well as other public sources of information,
SYS-CON Events announced today that SoftLayer, an IBM Company, has been named “Gold Sponsor” of SYS-CON's 18th Cloud Expo, which will take place on June 7-9, 2016, at the Javits Center in New York, New York. SoftLayer, an IBM Company, provides cloud infrastructure as a service from a growing number of data centers and network points of presence around the world. SoftLayer’s customers range from Web startups to global enterprises.
SYS-CON Events announced today that Ocean9will exhibit at SYS-CON's 20th International Cloud Expo®, which will take place on June 6-8, 2017, at the Javits Center in New York City, NY. Ocean9 provides cloud services for Backup, Disaster Recovery (DRaaS) and instant Innovation, and redefines enterprise infrastructure with its cloud native subscription offerings for mission critical SAP workloads.
Have you ever noticed how some IT people seem to lead successful, rewarding, and satisfying lives and careers, while others struggle? IT author and speaker Don Crawley uncovered the five principles that successful IT people use to build satisfying lives and careers and he shares them in this fast-paced, thought-provoking webinar. You'll learn the importance of striking a balance with technical skills and people skills, challenge your pre-existing ideas about IT customer service, and gain new in...
SYS-CON Events announced today that Juniper Networks (NYSE: JNPR), an industry leader in automated, scalable and secure networks, will exhibit at SYS-CON's 20th International Cloud Expo®, which will take place on June 6-8, 2017, at the Javits Center in New York City, NY. Juniper Networks challenges the status quo with products, solutions and services that transform the economics of networking. The company co-innovates with customers and partners to deliver automated, scalable and secure network...
Interoute has announced the integration of its Global Cloud Infrastructure platform with Rancher Labs’ container management platform, Rancher. This approach enables enterprises to accelerate their digital transformation and infrastructure investments. Matthew Finnie, Interoute CTO commented “Enterprises developing and building apps in the cloud and those on a path to Digital Transformation need Digital ICT Infrastructure that allows them to build, test and deploy faster than ever before. The int...
In his session at @ThingsExpo, Eric Lachapelle, CEO of the Professional Evaluation and Certification Board (PECB), will provide an overview of various initiatives to certifiy the security of connected devices and future trends in ensuring public trust of IoT. Eric Lachapelle is the Chief Executive Officer of the Professional Evaluation and Certification Board (PECB), an international certification body. His role is to help companies and individuals to achieve professional, accredited and worldw...
VeriStor Systems has announced that CRN has named VeriStor to its 2017 Managed Service Provider (MSP) 500 list in the Elite 150 category. This annual list recognizes North American solution providers with cutting-edge approaches to delivering managed services. Their offerings help companies navigate the complex and ever-changing landscape of IT, improve operational efficiencies, and maximize their return on IT investments. In today’s fast-paced business environments, MSPs play an important role...
DevOps is often described as a combination of technology and culture. Without both, DevOps isn't complete. However, applying the culture to outdated technology is a recipe for disaster; as response times grow and connections between teams are delayed by technology, the culture will die. A Nutanix Enterprise Cloud has many benefits that provide the needed base for a true DevOps paradigm. In his Day 3 Keynote at 20th Cloud Expo, Chris Brown, a Solutions Marketing Manager at Nutanix, will explore t...
What if you could build a web application that could support true web-scale traffic without having to ever provision or manage a single server? Sounds magical, and it is! In his session at 20th Cloud Expo, Chris Munns, Senior Developer Advocate for Serverless Applications at Amazon Web Services, will show how to build a serverless website that scales automatically using services like AWS Lambda, Amazon API Gateway, and Amazon S3. We will review several frameworks that can help you build serverle...
SYS-CON Events announced today that Linux Academy, the foremost online Linux and cloud training platform and community, will exhibit at SYS-CON's 20th International Cloud Expo®, which will take place on June 6-8, 2017, at the Javits Center in New York City, NY. Linux Academy was founded on the belief that providing high-quality, in-depth training should be available at an affordable price. Industry leaders in quality training, provided services, and student certification passes, its goal is to c...
SYS-CON Events announced today that Interoute, owner-operator of one of Europe's largest networks and a global cloud services platform, has been named “Bronze Sponsor” of SYS-CON's 20th Cloud Expo, which will take place on June 6-8, 2017 at the Javits Center in New York, New York. Interoute is the owner-operator of one of Europe's largest networks and a global cloud services platform which encompasses 12 data centers, 14 virtual data centers and 31 colocation centers, with connections to 195 add...
SYS-CON Events announced today that Telecom Reseller has been named “Media Sponsor” of SYS-CON's 20th International Cloud Expo, which will take place on June 6–8, 2017, at the Javits Center in New York City, NY. Telecom Reseller reports on Unified Communications, UCaaS, BPaaS for enterprise and SMBs. They report extensively on both customer premises based solutions such as IP-PBX as well as cloud based and hosted platforms.
FinTech is the sum of financial and technology, and it’s one of the fastest growing tech industries. Total global investments in FinTech almost reached $50 billion last year, but there is still a great deal of confusion over what it is and what it means – especially as it applies to retirement. Building financial startups is not simple, but with the right team, technology and an innovative approach it can be an extremely interesting domain to disrupt. FinTech heralds a financial revolution that...
Keeping pace with advancements in software delivery processes and tooling is taxing even for the most proficient organizations. Point tools, platforms, open source and the increasing adoption of private and public cloud services requires strong engineering rigor - all in the face of developer demands to use the tools of choice. As Agile has settled in as a mainstream practice, now DevOps has emerged as the next wave to improve software delivery speed and output. To make DevOps work, organization...