ViiV Healthcare announces FDA approval of an expanded indication for Dovato (dolutegravir/lamivudine), a complete two-drug regimen for virologically suppressed adults with HIV-1

ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer Inc. and Shionogi Limited as shareholders, today announced that the US Food and Drug Administration (FDA) approved Dovato (dolutegravir/lamivudine) as a complete regimen for the treatment of HIV-1 infection to replace the current antiretroviral (ARV) regimen in adults who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known resistance to the individual components of Dovato.

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Dovato Product Shot (Photo: Business Wire)

Dovato, a complete, once-daily, single-tablet, two-drug regimen of dolutegravir (DTG) 50 mg and lamivudine (3TC) 300 mg, allows adults living with HIV the option to manage their virus without a third ARV. It is free of tenofovir alafenamide fumarate (TAF), tenofovir disoproxil fumarate (TDF) and abacavir (ABC). Dovato was first approved by the FDA in April 2019 as a complete regimen for the treatment of HIV-1 infection in adults with no ARV treatment history and with no known resistance to the individual components of Dovato.

Lynn Baxter, Head of North America, ViiV Healthcare, said: “As HIV treatment and care progress, people living with HIV will be on medication for decades and need solutions to challenges that may arise from prolonged use of ARV therapy. At ViiV Healthcare, we’ve proven that with Dovato, adults living with HIV can reduce the number of ARVs they take every day without compromising efficacy or barrier to resistance. This remarkable, innovative approach challenges the notion that three or more drugs are needed to maintain virologic suppression, and today’s FDA approval brings this switch treatment option to virologically suppressed adults living with HIV.”

The approval of Dovato in adults who are virologically suppressed is based on the Week 48 results from the phase III TANGO study. This study demonstrated adults living with HIV-1, who had maintained virologic suppression for at least six months on a TAF-containing regimen of at least three drugs, were able to maintain similar rates of virologic suppression after switching to Dovato, compared with those who continued the original regimen. No participants on Dovato and one participant (<1%) on the TAF-containing regimen met confirmed virologic failure criteria, with no resistance mutations observed at failure. The safety results for those who switched to Dovato were consistent with the product labeling for dolutegravir and lamivudine.¹

Dr. Charlotte-Paige Rolle, Director of Research Operations, Orlando Immunology Center, said: “This expanded approval for Dovato is particularly important for my virologically suppressed patients living with HIV who are seeking a new option that can reduce the number of drugs they are exposed to each day. The data supporting the approval demonstrates how virologically suppressed adults with no known resistance to dolutegravir or lamivudine were able to switch from a TAF-containing regimen of at least three drugs to Dovato while maintaining similar efficacy with zero cases of treatment-emergent resistance through 48 weeks.”

Dovato is approved for the treatment of HIV-1 in treatment-naïve and virologically suppressed adults by the European Medicines Agency and additional regulatory authorities around the world. In 2019, the Adult and Adolescent Antiretroviral Treatment Guidelines from the Department of Health and Human Services (DHHS) included Dovato in the list of Recommend Initial Regimens for Most People with HIV, the first time a complete two-drug regimen has been recommended by the DHHS in the first-line setting (except in individuals with HIV RNA >500,000 copies/ml, HBV co-infection, or in whom ART is to be started before the results of the HIV genotypic resistance testing for RT or HBV testing are available).²

About Dovato (dolutegravir/lamivudine)

Dolutegravir is an integrase strand transfer inhibitor (INSTI) for use in combination with other antiretroviral agents for the treatment of HIV-1. INSTIs 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 authorized in more than 100 countries across North America, Europe, Asia, 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-1 infection. Lamivudine is available in branded and generic forms.

Dolutegravir plus lamivudine (Dovato) is a complete, once-daily, single-tablet regimen to treat HIV-1 infection in adults with no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RN <50 copies/mL) on a stable ARV regimen with no known history of treatment failure and no known resistance to any component of Dovato.

Trademarks are owned by or licensed to the ViiV Healthcare group of companies.

About TANGO

TANGO (NCT03446573) is a phase III, randomized, open-label, active-controlled, multicenter study to assess the antiviral efficacy and safety of switching to a two-drug regimen consisting of DTG/3TC in HIV-infected adults who are virologically suppressed and on a stable antiretroviral regimen with no treatment failure.

Study participants were HIV-1 infected adults on a TAF-containing regimen with HIV-1 RNA<50c/mL for at least six months, without prior virologic failure, no historical nucleoside reverse transcriptase inhibitors (NRTI) or integrase strand transfer inhibitor (INSTI) major resistance mutation, and no evidence of hepatitis B infection. Participants were randomized to switch to DTG/3TC or continue on the TAF-containing 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 Intention To Treat-Exposed (ITT-E) population. In the primary analysis, no participants on Dovato and one participant (<1%) on the TAF-containing regimen met confirmed virologic failure criteria, with no resistance mutations observed at failure.

Important Safety Information for Dovato

The following ISI 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. Avoid use of Dovato at the time of conception through the first trimester of pregnancy due to the risk of neural tube defects. Advise 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).

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 and 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 ViiV Healthcare’s Patient Support Program

ViiV Healthcare is committed to providing assistance to eligible people living with HIV who need our medicines. ViiV Healthcare’s centralised service, ViiV Connect, provides comprehensive information on access and coverage to help patients get their prescribed ViiV Healthcare medicines whether they are insured, underinsured or uninsured. ViiV Connect provides one-on-one support from dedicated access coordinators, as well as having an integrated website, one site with many resources, including a portal. For more information on ViiV Connect, visit www.viivconnect.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/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 any impacts of the COVID-19 pandemic.

¹ Dovato (dolutegravir/lamivudine) Prescribing Information. US Approval 2020.

² Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services. December 2019.

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