LONDON, UK I July 24, 2019 I ViiV Healthcare, the global specialist HIV company majority-owned by GSK, with Pfizer Inc. and Shionogi Limited as shareholders, today announced Week 96 results from its phase III GEMINI 1 & 2 studies, which showed that the 2-drug regimen (2DR) of dolutegravir plus lamivudine continued to offer non-inferior efficacy to a 3-drug regimen of dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs), tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) with no cases of treatment emergent resistance in individuals with virologic failure.1 The data were presented today at the 10th International AIDS Society Conference on HIV Science (IAS 2019) in Mexico City.
Both the GEMINI 1 & 2 studies showed that dolutegravir plus lamivudine continued to offer non-inferior efficacy to dolutegravir plus TDF/FTC at Week 96.1 A pooled analysis of the two studies at Week 96 showed that 86% (616/716) in the dolutegravir plus lamivudine arm had HIV-1 RNA <50 copies per millilitre (c/mL) compared with 90% (642/717) in the dolutegravir plus TDF/FTC arm (adjusted difference -3.4 [6.7, 0.0]).1
Across both studies, 11 participants (1.5%) on dolutegravir plus lamivudine and seven (1.0%) on dolutegravir plus TDF/FTC met protocol-defined virologic withdrawal criteria through to Week 96.1 No patient who experienced confirmed virologic withdrawal in either treatment arm developed treatment-emergent resistance.1
Pedro Cahn, M.D., principal investigator for the GEMINI study programme, said: “The Week 96 data from the GEMINI studies demonstrate that the clinical benefits of dolutegravir plus lamivudine we saw at Week 48 are sustainable, allowing us to use these two drugs while still getting efficacy non-inferior to that of a dolutegravir-based 3-drug regimen. This provides further evidence for the benefits of this dolutegravir-based 2-drug regimen in a treatment-naïve population, and enables physicians and people living with HIV to be confident in the durability of this treatment option. These latest findings are important for people living with HIV who will potentially spend decades taking medication to manage their HIV.”
Results at Week 96 showed that response rates for viral suppression in participants with a baseline viral load of more than 100,000 copies of viral RNA per millilitre of blood plasma (>100,00 c/mL) were similar between the dolutegravir plus lamivudine arm and the dolutegravir plus TDF/FTC arm (GEMINI 1: 81% (60/74) compared to 88% (67/76) in the respective arms [unadjusted difference -7.1 (-18.6,4.4)]; GEMINI 2: 86% (57/66) compared to 84% (65/77) in the respective arms [unadjusted difference 1.9 (-9.6,13.5)]).1
Consistent with Week 48 outcomes, the response rate remained lower in dolutegravir plus lamivudine participants with CD4+ ≤ 200 cells/mm3, (GEMINI 1: 65% (20/31) compared to 90% (26/29) in the respective arms [unadjusted difference -25.1 (-45.3,-5.0)] GEMINI 2: 72% (23/32 compared to 85% (22/26) [unadjusted difference -12.7 (-33.6,8.1)] in the respective arms).1 However, in the majority of cases treatment discontinuation in these individuals was unrelated to the treatment regimen.1
In the pooled study population, the most common (≥5%) drug-related adverse events (AEs) were nasopharyngitis, diarrhoea and headache in both arms (dolutegravir plus lamivudine arm: 10%, 12%, and 11%, respectively, dolutegravir plus TDF/FTC: 16%, 13%, and 12%, respectively).1 Drug-related AEs occurred less frequently in participants on the dolutegravir plus lamivudine arms compared with those in the dolutegravir plus TDF/FTC arms (140/716, [20%] vs 179/717 [25%] respectively).1 Rates of serious AEs were comparable (64/716 [9%] vs 67/717 [9%] in the dolutegravir plus lamivudine arms versus the dolutegravir plus TDF/FTC arms).1 The percentage of participants who withdrew due to AEs was 3% in each study arm (24/716 in the dolutegravir plus lamivudine arm vs 23/717 in the dolutegravir plus TDF/FTC arms).1
Kimberly Smith, M.D., Head of Global Research & Medical Strategy at ViiV Healthcare, said: “The GEMINI 1 & 2 studies have already changed the way we treat people living with HIV, with the combination of dolutegravir plus lamivudine allowing many people to reduce the number of medicines they take and manage their HIV without a third antiretroviral treatment. The Week 96 data further demonstrate the durable efficacy and tolerability of dolutegravir plus lamivudine.”
The single-pill combination of dolutegravir plus lamivudine was authorised under the brand name Dovato in the United States earlier this year for the treatment of HIV-1 infection in adults with no antiretroviral treatment history and with no known resistance to either dolutegravir or lamivudine.2 It was also authorised this month in Europe 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 integrase inhibitor (INI) class, or lamivudine.3 Further regulatory marketing applications have been submitted worldwide.
About GEMINI 1 & 2
GEMINI 1 (204861) & GEMINI 2 (205543) are duplicate, phase III, randomised, double-blind, multicentre, parallel group, non-inferiority studies, part of ViiV Healthcare’s innovative clinical trial programme. These studies evaluate a 2DR 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 up to 500,000 c/mL. The studies are 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.4,5
For more information please search for NCT02831673 (GEMINI 1) or NCT02831764 (GEMINI 2) on www.clinicaltrials.gov.
About dolutegravir and lamivudine
Dolutegravir is an INI for use in combination with other antiretroviral agents for the treatment of HIV.6 INIs 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 and is also responsible for establishing chronic infection. Dolutegravir is authorised in more than 100 countries across North America, Europe, Asia, Australia, Africa and Latin America.
Lamivudine, commonly known as 3TC, is a nucleoside analogue used in combination with other antiretroviral agents for the treatment of HIV infection. Lamivudine is available in branded and generic forms.7
Dolutegravir plus lamivudine (Dovato) is a once-daily, single-pill, 2-drug regimen that combines the INI dolutegravir 50 mg with the NRTI lamivudine 300 mg.2 It 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,3 and in the US for the treatment of HIV-1 infection in adults with no antiretroviral treatment history and with no known resistance to either dolutegravir or lamivudine.2
Trademarks are owned by or licensed to the ViiV Healthcare group of companies.
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.
References
1 Cahn, P 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 10 International AIDS Conference on HIV Science (IAS 2019), 21-24th July 2019, Mexico City, Mexico.
2 Dolutegravir plus lamivudine Prescribing Information. U.S. Approval 8 April 2019. Available at: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Dovato/pdf/DOVATO-PI-PIL.PDF Accessed July 2019
3 Dovato EU Summary of Product Characteristics. July 2019. Available at: https://www.medicines.org.uk/emc/product/10446/smpc Accessed July 2019.
4 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 July 2019.
5 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 July 2019.
6 Tivicay (dolutegravir) European Summary of Product Characteristics. Available at: https://www.ema.europa.eu/documents/product-information/tivicay- epar -product-information_en.pdf. Accessed July 2019.
7 European Medicines Agency. Epivir (lamivudine) European Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/epivir-epar-product-information_en.pdf Accessed July 2019.
SOURCE: ViiV Healthcare
