ViiV Healthcare announces phase III study meets primary endpoint, demonstrating the ability to control HIV-1 with the 2-drug regimen Dovato (dolutegravir plus lamivudine) in virally suppressed patients switching from a TAF-containing, 3-drug regimen

Issued: London, UK

ViiV Healthcare, the global specialist HIV company majority-owned by GSK, with Pfizer Inc. and Shionogi Limited as shareholders, today announced positive Week 48 results from its phase III TANGO study. The TANGO study was conducted to assess whether adults living with HIV-1 who had maintained viral suppression for at least six months on a tenofovir alafenamide fumarate (TAF)-containing regimen of at least three drugs, were able to maintain similar rates of viral suppression after switching to Dovato (dolutegravir plus lamivudine), compared to continuing the TAF-containing regimen.

The study met its primary endpoint for non-inferiority, based on the proportion of participants with plasma HIV-1 RNA ≥50 copies per milliliter (c/mL) using the FDA Snapshot algorithm at Week 48. No patients met confirmed virologic withdrawal criteria or developed treatment resistance in the dolutegravir plus lamivudine arm of the study. The safety results for Dovato were consistent with the product labelling for the medicines.^[1]

Full results from the study will be presented at the 10^th International AIDS Society Conference on HIV Science (IAS 2019), to be held from 21-24 July in Mexico City.

Kimberly Smith, M.D., Head of Global Research & Medical Strategy at ViiV Healthcare, said: “When we developed the TANGO study, we asked if virally suppressed people living with HIV could reduce the number of medicines in their HIV treatment regimen while maintaining viral suppression. These Week 48 data clearly indicate that they can – individuals who are already on treatment can maintain viral suppression if they switch from a 3-drug, TAF-containing regimen to Dovato.” 

Dovato was authorized in the United States earlier this year for the treatment of HIV-1 infection in adults with no antiretroviral treatment (ARV) history and with no known resistance to either dolutegravir or lamivudine.^[2]

About TANGO

TANGO is a phase III, randomized, open-label, active-controlled, multicenter study to assess the antiviral efficacy and safety of switching to Dovato in HIV-infected adults who are virally suppressed and stable on a TAF-containing regimen.^[3]

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 INI major resistance mutation, and no evidence of hepatitis B infection. Participants were randomized to switch to Dovato 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.^[3]

About Dovato (dolutegravir plus lamivudine)

Dovato is approved as a complete regimen for the treatment of HIV-1 infection in adults with no known antiretroviral treatment history and with no known substitutions associated with resistance to either dolutegravir or lamivudine. Dovato is a once-daily, single-tablet, two-drug regimen that combines the integrase inhibitor (INI) dolutegravir (Tivicay, 50 mg) with the nucleoside analogue reverse transcriptase inhibitor (NRTI) lamivudine (Epivir, 300 mg).^[2]

Like a dolutegravir-based 3-drug regimen, Dovato uses only 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 RNA into DNA which in turn stops the virus from multiplying.

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

Important Safety Information (ISI)

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 characterised 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, diarrhea, nausea, insomnia, and fatigue.

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: Avoid use of DOVATO 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 aims 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/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 'Principal risks and uncertainties' in the company's Annual Report on Form 20-F for 2018.

References

[1] ViiV Healthcare: TANGO headline results. Data on file.

[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] 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 June 2019