VIIV-HEALTHCARE

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 & 2 ^1,2,3,4
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.

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References

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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.

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