VIIV-HEALTHCARE

ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer Inc. and Shionogi Limited as shareholders, today announced 96-week data from the TANGO study at the HIV Glasgow 2020 congress showing that the 2-drug regimen (2DR) Dovato (dolutegravir/lamivudine) continued to demonstrate non-inferior efficacy compared to continuation of a tenofovir alafenamide fumarate (TAF)-based regimen of at least three drugs in virologically suppressed adults with HIV-1 who have not previously experienced virologic failure.¹ Data from the study revealed that no participants on Dovato (0/369, 0%) and three participants (3/372, <1%) on the TAF-based regimen met protocol-defined virologic failure, and no participants developed resistance mutations upon failure.¹

Professor Stéphane De Wit, M.D., Head, Infectious Diseases, Saint Pierre University Hospital, Brussels, and investigator for the TANGO study, said: “For physicians who have been waiting for long-term data on dolutegravir/lamivudine in virologically suppressed adults with HIV, the TANGO 96-week results show that it maintains the efficacy and resistance profile seen in earlier presentations of the study findings. It is also significant to see that in such a large pivotal study, no one experienced virologic failure in the two years that it has been running. These data help to build our understanding of dolutegravir/lamivudine as a complete regimen and expand its strong evidence base, providing clinicians with more confidence to switch from TAF-based 3-drug regimens to dolutegravir/lamivudine.”

Week 96 findings from the TANGO study showed that switching to Dovato was non-inferior to continuing a TAF-based regimen in the Intention to Treat-Exposed (ITT-E) analysis (defined as all participants randomised to the study), based on the proportion of participants with plasma HIV-1 RNA ≥50 copies per millilitre (c/mL) at Week 96 (Snapshot virologic failure: <1% vs 1%; adjusted difference: -0.8% [95% CI: -2.0%, 0.4%]).¹ In the Per-Protocol analysis (defined as participants who completed the study to 96 weeks), Dovato was shown to be superior to the TAF-based regimen arm (0% vs 1%; adjusted difference: -1.1% [95% CI: -2.3%, -0.0%]).¹

The proportion of participants with plasma HIV-1 RNA <50 c/mL was high in both arms and demonstrated non-inferiority in 86% ([317/369] of participants in the Dovato arm vs 79% [294/372] in the TAF-based regimen arm; adjusted difference: 6.8% [95% CI: 1.4%, 12.3%]).¹

Kimberly Smith, M.D., MPH, Head of Research & Development at ViiV Healthcare, said: “Today’s findings from the TANGO study provide more evidence that people living with HIV can keep their virus under control with a dolutegravir-based 2-drug regimen, reflecting the consistent results that we’re seeing in real-world cohorts. Following on from the GEMINI 1 & 2 results presented earlier this week for treatment-naïve adults, these results continue to support the inclusion of Dovato as a recommended therapy in international HIV treatment guidelines.”

Overall adverse event (AE) rates were similar between the two study arms, with more drug-related grade 2-5 AEs in the Dovato arm (6% [21/369]) vs the TAF-based regimen arm (2% [7/371]). Rates of adverse events were similar between treatment arms at both Week 48 and Week 96.¹ Fasting lipids were similar to findings seen at Week 48 and generally in favour of Dovato: total cholesterol (TC), low-density lipoprotein (LDL) and triglycerides showed significant differences favouring the Dovato arm, while high-density lipoprotein (HDL) cholesterol changes significantly favoured TAF-based regimens, with no difference in TC/HDL ratios between arms.¹ The Week 96 findings also showed indications of better renal function outcomes in the Dovato arm; decreases in glomerular filtration rate (GFR) by cystatin-C^* were observed in both arms, with a significantly smaller decrease in the Dovato arm.¹ The clinical significance of these changes in biomarkers is unknown.

About TANGO ^{1, 2}

TANGO is a phase III, randomised, open-label, active-controlled, multicentre study to assess the antiviral efficacy and safety of switching to a 2-drug regimen (2DR) consisting of dolutegravir/lamivudine in HIV-infected adults who are virologically suppressed and stable on a TAF-based regimen.

Study participants were HIV-1 infected adults on a TAF-based regimen with HIV-1 RNA<50 c/mL for at least six months, without prior virologic failure, no historical nucleoside reverse transcriptase inhibitors (NRTI) or integrase inhibitor (INI) major resistance mutation, and no evidence of hepatitis B infection. Participants were randomised to switch to dolutegravir/lamivudine or continue on the TAF-based regimen through Week 148. The primary endpoint was the proportion of participants with a viral load of >50 c/mL at Week 48 (FDA Snapshot algorithm) for the ITT-E population.

About Dovato (dolutegravir/lamivudine) ^3,4

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

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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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^* Monitoring GFR by cystatin-C is a measure of renal function

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References

¹ van Wyk J., Ajana F., Bisshop F., et al. Switching to DTG/3TC fixed-dose combination (FDC) is non-inferior to continuing a TAF-based regimen (TBR) in maintaining virologic suppression through 96 Weeks (TANGO Study). Presented at HIV Glasgow 2020.
² Clinical trials.gov. Switch Study to Evaluate Dolutegravir Plus Lamivudine in Virologically Suppressed Human Immunodeficiency Virus Type 1 Positive Adults (TANGO). Available at: https://clinicaltrials.gov/ct2/show/NCT03446573?term=TANGO+dolutegravir&rank=1 . Accessed September 2020.
³ Dovato EU Summary of Product Characteristics. July 2019. Available at: https://www.medicines.org.uk/emc/product/10446/smpc . Accessed September 2020.
⁴ 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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