Business Wire

ViiV Healthcare announces dolutegravir plus lamivudine three-year data confirming long-term viral suppression non-inferior to a 3-drug regimen for treatment-naïve adults with HIV-1

Share

ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer Inc. and Shionogi Limited as shareholders, today presented three-year results from the phase III GEMINI 1 & 2 studies at the HIV Glasgow 2020 congress. Findings showed that the 2-drug regimen (2DR) of dolutegravir plus lamivudine continued to offer non-inferior efficacy, a high genetic barrier to resistance and a comparable safety profile versus a 3-drug regimen of dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs), tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), in treatment-naïve adults with HIV-1.1

Pedro Cahn, M.D., Scientific Director, Fundación Huésped, Professor of Infectious Diseases, Buenos Aires University Medical School, and principal investigator for the GEMINI study programme, said: “These long-term data confirm that dolutegravir-based 2-drug regimens have a rightful place in the HIV treatment compendium. Dolutegravir plus lamivudine continues to demonstrate long-term non-inferior efficacy compared to dolutegravir plus TDF/FTC with benefits beyond viral suppression. While overall adverse event rates were similar across the study arms, we saw fewer drug-related adverse events with dolutegravir plus lamivudine. Clinicians who wanted proof that a dolutegravir-based 2-drug regimen works long-term in treatment-naïve adults with HIV now have evidence to show that it does.”

A pooled analysis of the two studies showed that dolutegravir plus lamivudine demonstrated non-inferiority, with 82% (584/716) of participants in the Snapshot analysis – Intention to Treat-Exposed (ITT-E) population having HIV-1 RNA <50 copies per millilitre (c/mL) at Week 144, compared with 84% (599/717) of participants receiving a 3-drug regimen of dolutegravir plus TDF/FTC (adjusted difference: -1.8 [95% CI: -5.8%, 2.1%]).1 Safety and tolerability findings were consistent with previous data.1,2

Kimberly Smith, M.D., MPH, Head of Research & Development at ViiV Healthcare, said: “Globally, the number of people living with HIV aged 50 and over is increasing and that’s testament to the success of antiretroviral therapy, which has transformed HIV into a chronic condition. However, living longer with HIV can mean taking multiple medications for many years, and we know that many people living with HIV have a preference to take as few medicines as possible, as long as their HIV remains under control. The momentum behind 2DRs is growing: Dovato has now shown sustained efficacy and tolerability through three years of treatment, with people able to maintain viral suppression with fewer medicines than a 3-drug regimen.”

Dolutegravir plus lamivudine continued to demonstrate a high genetic barrier to treatment-emergent resistance. The percentage of individuals with protocol-defined confirmed virologic withdrawal (CVW) was 1.7% (12/716) in the dolutegravir plus lamivudine arm and 1.3% (9/717) in the dolutegravir plus TDF/FTC arm.1 None of these participants developed treatment-emergent resistance mutations. One non-CVW participant receiving dolutegravir plus lamivudine with reported non-adherence to treatment developed M184V and R263R/K resistance mutations before discontinuing the study.1

Overall adverse event (AE) rates were similar between the study arms, with lower rates of drug-related AEs in participants receiving dolutegravir plus lamivudine compared with those receiving dolutegravir plus TDF/FTC (20% [146/716] vs 27% [192/717], respectively).1 Four deaths occurred (3/716 for dolutegravir plus lamivudine vs 1/717 for dolutegravir plus TDF/FTC), all of which were considered unrelated to the study drug regimen.1 The study findings showed potential for long-term bone and renal health outcomes, with post-baseline changes in markers of bone and renal function continuing to favour dolutegravir plus lamivudine compared to dolutegravir plus TDF/FTC through Week 144.1

About GEMINI 1 & 21,2,3,4
GEMINI 1 (204861) & GEMINI 2 (205543) are duplicate, phase III, randomised, double-blind, multicentre, parallel group, non-inferiority studies, and part of ViiV Healthcare’s innovative clinical trial programme. These studies evaluate a 2-drug regimen of dolutegravir plus lamivudine compared with a 3-drug regimen of dolutegravir plus TDF/FTC in HIV-1 infected, antiretroviral treatment-naïve adult participants with baseline HIV-1 viral loads between 1,000 and 500,000 c/mL. The studies were designed to demonstrate the non-inferior efficacy at Week 48, as well as the safety and tolerability of once-daily dolutegravir plus lamivudine compared to once-daily dolutegravir plus the fixed-dose combination of TDF/FDC in HIV-1-infected, antiretroviral treatment-naïve adult participants. The primary endpoint was the proportion of participants with HIV-1 RNA plasma <50c/mL at Week 48; secondary endpoints included the proportion of participants with HIV-1 RNA plasma <50c/mL at Weeks 24, 96 and 144.

For more information please search for NCT02831673 (GEMINI 1) or NCT02831764 (GEMINI 2) on www.clinicaltrials.gov.

About Dovato (dolutegravir/lamivudine)5,6
Dovato is a once-daily, single-pill, 2-drug regimen (2DR) that combines the integrase strand transfer inhibitor (INI) dolutegravir (Tivicay, 50 mg) with the NRTI lamivudine (Epivir, 300 mg).

Dovato (dolutegravir 50 mg/ lamivudine 300 mg tablets) is authorised in the EU for the treatment of HIV-1 infection in adults and adolescents above 12 years of age weighing at least 40 kg, with no known or suspected resistance to the INI class, or lamivudine. In the US, Dovato is indicated as a complete regimen to treat HIV-1 infection in adults with no ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable ARV regimen with no history of treatment failure and no known resistance to any component of Dovato.

Like a dolutegravir-based three-drug regimen, Dovato uses two drugs to inhibit the viral cycle at two different sites. INIs, like dolutegravir, inhibit 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. Lamivudine is an NRTI that works by interfering with the conversion of viral ribonucleic acid (RNA) into deoxyribonucleic acid (DNA) which in turn stops the virus from multiplying.

Dovato is approved in the US, Europe, Japan and other countries worldwide. Trademarks are owned by or licensed to the ViiV Healthcare group of companies.

Important Safety Information for Dovato
The following safety information is based on the Highlights section of the Prescribing Information for Dovato. Please consult the full Prescribing Information for all the labeled safety information for Dovato.

WARNING: PATIENTS CO-INFECTED WITH HEPATITIS B VIRUS (HBV) AND HUMAN IMMUNODEFICIENCY VIRUS (HIV-1): EMERGENCE OF LAMIVUDINE-RESISTANT HBV AND EXACERBATIONS OF HBV

  • All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating Dovato. Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens has been reported. If Dovato is used in patients co-infected with HIV-1 and HBV, additional treatment should be considered for appropriate treatment of chronic HBV; otherwise, consider an alternative regimen
  • Severe acute exacerbations of HBV have been reported in patients who are co-infected with HIV-1 and HBV and have discontinued lamivudine, a component of Dovato. Closely monitor hepatic function in these patients and, if appropriate, initiate anti-HBV treatment

DOSAGE AND ADMINISTRATION

  • Prior to or when initiating Dovato, test patients for HBV infection.
  • Pregnancy Testing: Perform pregnancy testing before initiation of Dovato in individuals of childbearing potential
  • One tablet taken orally once daily with or without food
  • The dolutegravir dose (50 mg) in Dovato is insufficient when coadministered with carbamazepine or rifampin. If Dovato is coadministered with carbamazepine or rifampin, take one tablet of Dovato once daily, followed by an additional dolutegravir 50-mg tablet, approximately 12 hours from the dose of Dovato

CONTRAINDICATIONS

  • Prior hypersensitivity reaction to dolutegravir or lamivudine
  • Coadministration with dofetilide

WARNINGS AND PRECAUTIONS

  • Hypersensitivity reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury, have been reported with dolutegravir. Discontinue Dovato 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 a dolutegravir-containing regimen. Patients with underlying hepatitis B or C may be at increased risk for worsening or development of transaminase elevations with Dovato. 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 Dovato should be considered at the time of conception through the first trimester of pregnancy due to the risk of neural tube defects. Counsel individuals of childbearing potential to use effective contraception
  • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues
  • Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy

ADVERSE REACTIONS

The most common adverse reactions (all grades) observed in ≥2% (in those receiving Dovato) were headache, nausea, diarrhea, insomnia, fatigue, and anxiety.

DRUG INTERACTIONS

  • Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended
  • Refer to the full prescribing information for important drug interactions with Dovato

USE IN SPECIFIC POPULATIONS

  • Pregnancy: An alternative treatment to Dovato 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 individuals of childbearing potential
  • Renal Impairment: Dovato is not recommended in patients with creatinine clearance less than 50 mL/min
  • Hepatic Impairment: Dovato is not recommended in patients with severe hepatic impairment (Child-Pugh Score C)

Please refer to the full European Summary of Product Characteristics for Dovato for full prescribing information, including contraindications, special warnings and precautions for use. For the US, please refer to the US Prescribing Information.

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 aims are 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 https://www.gsk.com/en-gb/about-us/.

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 Q2 Results and any impacts of the COVID-19 pandemic.

Registered in England & Wales:
No. 3888792

Registered Office:
980 Great West Road
Brentford, Middlesex
TW8 9GS

References


1 Cahn P., Sierro Madera J., Arribas J, et al. Durable efficacy of dolutegravir (DTG) plus lamivudine (3TC) in antiretroviral treatment-naïve adults with HIV-1 infection – 3-year results from the GEMINI studies. Presented at HIV Glasgow 2020.
2 Cahn P., Sierro Madera J., Arribas J, et al. Durable efficacy of dolutegravir (DTG) plus lamivudine (3TC) in antiretroviral treatment-naïve adults with HIV-1 infection - 96-week results from the GEMINI studies. Presented at the 10th International AIDS Conference on HIV Science (IAS 2019), 21-24th July 2019, Mexico City, Mexico.
3 Clinical trials.gov. An efficacy, safety, and tolerability study comparing dolutegravir plus lamivudine with dolutegravir plus tenofovir/emtricitabine in treatment naïve HIV infected subjects (Gemini 1). NCT02831673. Available at https://clinicaltrials.gov/ct2/show/NCT02831673?term=204861&rank=1. Accessed September 2020.
4 Clinical trials.gov. An efficacy, safety, and tolerability study comparing dolutegravir (DTG) plus lamivudine (3TC) with dolutegravir plus tenofovir/emtricitabine in treatment naïve HIV infected subjects (Gemini 2). NCT02831764. Available at https://clinicaltrials.gov/ct2/show/NCT02831764?term=NCT02831764&rank=1. Accessed September 2020.
5 Dovato EU Summary of Product Characteristics. July 2019. Available at: https://www.medicines.org.uk/emc/product/10446/smpc. Accessed September 2020.
6 Dovato US Prescribing Information. Available at: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Dovato/pdf/DOVATO-PI-PIL.PDF. Accessed September 2020.

Contact information

ViiV Healthcare media enquiries:
Patricia O’Connor +44 20 8047 5982 (UK)
Audrey Abernathy +1 919 605 4521 (US)

GSK enquiries:
Media enquiries:
Simon Steel +44 (0) 20 8047 5502 (London)
Tim Foley +44 (0) 20 8047 5502 (London)
Kristen Neese +1 804 217 8147 (Philadelphia)
Kathleen Quinn +1 202 603 5003 (Washington DC)

Analyst/Investor enquiries:
Sarah Elton-Farr +44 (0) 20 8047 5194 (London)
Sonya Ghobrial +44 (0) 7392 784784 (Consumer)
Danielle Smith +44 (0) 20 8047 0932 (London)
James Dodwell +44 (0) 20 8047 2406 (London)
Jeff McLaughlin +1 215 751 7002 (Philadelphia)
Frannie DeFranco +1 215 751 4855 (Philadelphia)

About Business Wire

Business Wire
Business Wire
24 Martin Lane
EC4R 0DR London

+44 20 7626 1982http://www.businesswire.co.uk

(c) 2018 Business Wire, Inc., All rights reserved.

Business Wire, a Berkshire Hathaway company, is the global leader in multiplatform press release distribution.

Subscribe to releases from Business Wire

Subscribe to all the latest releases from Business Wire by registering your e-mail address below. You can unsubscribe at any time.

Latest releases from Business Wire

Cobase and Ebury partner on FX services1.12.2020 10:00:00 CETPress release

Leading European fintechs Cobase and Ebury today announce a partnership which opens up Ebury’s FX services to the Cobase multi-banking platform. Cobase, an innovative leader in cloud-based corporate multi-banking solutions, will offer its corporate treasury clients services from Ebury, a leading global FinTech backed by Santander Bank that specializes in cross-border financial services and risk management. The partnership follows the launch of Cobase’s new Liquidity Forecasting and FX Exposure Management modules, which enable corporate treasuries to optimize cash positions or automatically hedge their FX risk on a continuous basis. Adding Ebury’s services to Cobase’s platform will give clients broader access to more cost-effective FX services, and Cobase users will be able to receive competitive FX quotes from Ebury and book FX trades without the need to access any other system. Users will also be able to receive real-time status of transactions and reporting to automate the reconcilia

Sleep Cycle Partners with Petit BamBou For Global Relaxation1.12.2020 10:00:00 CETPress release

Sleep Cycle, the world’s most popular intelligent alarm clock app that analyzes users’ sleep, today announces its first partnership with one of the world’s leading meditation apps, Petit BamBou to provide its global users with relaxation content for better sleep during these uncertain times. Sleep Cycle will be hosting meditation content by Petit BamBou in their Sleep Aid program, which features a series of audio productions designed to aid in falling asleep. The content offers users an improved bedtime routine to help them relax and unwind before going to sleep for a better night’s rest. “Sleep is as much about physical health as it is about the well-being of the mind. Implementing a sleep routine that works in meditation can help prepare for a more restful sleep,” said Andreas Roman, head of content at Sleep Cycle. “By adding Petit BamBou’s meditation tracks to our carefully curated content library, we’re helping users find a place for meditation in their lives to reach a new level o

Henley & Partners: Covid-19 Accelerates Growth of Investment Migration Industry1.12.2020 10:00:00 CETPress release

There has been a 25% increase in the number of HNWIs enquiring about citizenship-by-investment as opposed to residence-by-investment programs since the coronavirus was first reported nearly a year ago, indicating that wealthy international investors are considering a more permanent change. Leading residence and citizenship advisory firm Henley & Partners has also reported an unprecedented and sustained surge in enquiries from citizens of highly developed countries such as Canada, the UK, and the US compared to last year, along with noticeable shifts in its clientele’s priorities. Henley & Partners CEO Dr. Juerg Steffen says that when combined with over a decade of growth in engagement from the buy and sell side, it’s fair to state that investment migration is now very much a mainstream (U)HNWI advisory service. “The value to both investors and their families, and sovereign states and their citizens, is very clear. The volume has also now reached a critical mass where it is reasonable t

iRhythm Technologies Receives Positive National Guidance in First of its Kind Digital Health Pilot with National Institute for Health and Care Excellence1.12.2020 09:30:00 CETPress release

iRhythm Technologies (NASDAQ: IRTC), a leading digital health care solutions company focused on the advancement of cardiac care, today announced it is the first technology to pass through a new digital health tech pilot, resulting in a successful recommendation for adoption from the National Institute for Health and Care Excellence (NICE). iRhythm’s Zio XT Service – a patient-friendly ambulatory cardiac monitor supported by deep learning algorithms – has been assessed as part of NICE’s first pilot project to evaluate digital health technologies. Zio XT has been positively recommended by NICE as an option for people with suspected cardiac arrhythmias who would benefit from ECG monitoring for longer than 24 hours. Published today, the guidance concluded that Zio XT is convenient and easy to wear, with greater patient compliance and improved diagnostic yield (a measure of how many people with cardiac arrhythmias are diagnosed) compared with standard 24-hour Holter monitoring. Clinical evi

ViiV Healthcare and Shutterstock Studios unite to tackle outdated perceptions of HIV with ‘HIV in View’ - a first-of-its-kind online HIV photography gallery1.12.2020 09:12:00 CETPress release

ViiV Healthcare and Shutterstock Studios today announced the launch of a new online photo gallery ‘HIV in View’,produced by Shutterstock in collaboration with ViiV Healthcare. The collection, curated with the support of people living with HIV, leverages Shutterstock’s global network of over one million creators to deliver a repository of high-resolution images depicting what it means to live with HIV today. Across four countries (the United Kingdom, Kenya, Uruguay, Portugal), people living with HIV stepped forward to be among the first photographed for this gallery, embarking on a shared ambition to help shift the world’s perception of HIV and move away from outdated stereotypes. From World AIDS Day 2020, the gallery will be free for all to access and use in projects, campaigns and communications* in the hope that it will increase awareness around HIV and break down barriers to stigma that still exist. This press release features multimedia. View the full release here: https://www.busi

ADVA joins Affordable5G to build high-performance and cost-effective mobile networks1.12.2020 09:00:00 CETPress release

ADVA (FSE: ADV) today announced that it has joined Affordable5G, an innovation project creating complete and affordable solutions for critical private and enterprise networks. Affordable5G aims to build open and flexible next-generation mobile solutions for use cases including campus networks, emergency communications and smart city services. Funded by Horizon 2020 and part of the European 5G Public-Private Partnership (5G PPP), the project brings together 17 partners with a wide range of expertise and disruptive technology spanning all areas of the 5G ecosystem. ADVA’s X-Haul technology will be central to the project and the development of 5G infrastructure. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20201201005086/en/ ADVA’s X-Haul technology will prove key to the Affordable5G project (Photo: Business Wire) “5G enterprise networks must meet a particularly demanding set of bandwidth and performance requirements. Not only