ViiV Healthcare Submits Supplemental New Drug Application to US FDA for Use of Dovato in Virologically Suppressed Adults with HIV-1
The filing is based on the results from the phase III TANGO study, which demonstrated adults living with HIV-1, who had maintained virologic 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 virologic suppression after switching to the two-drug regimen (2DR) Dovato, compared to those who continued the TAF-containing regimen. The safety results for those who switched to Dovato were consistent with the product labeling for DTG and 3TC.1
TANGO (NCT03446573) is a phase III, randomized, open-label, active-controlled, multicenter study to assess the antiviral efficacy and safety of switching to a 2DR consisting of DTG/3TC in HIV-infected adults who are virologically suppressed and on a stable antiretroviral regimen with no treatment failure.2
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 inhibitor (INI) 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.2
About Dovato (dolutegravir and lamivudine)
Dolutegravir is an INI for use in combination with other antiretroviral agents for the treatment of HIV-1.3 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 authorized in more than 100 countries across
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.4
Dolutegravir plus lamivudine (Dovato) is a complete, once-daily, single-tablet regimen of DTG 50 mg and 3TC 300 mg for the treatment of HIV-1 infection in adults with no antiretroviral treatment history and with no known resistance to either DTG or 3TC. Use of Dovato in virologically suppressed adults on a stable antiretroviral regimen with no treatment failure replacing their current therapy is subject to
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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.
- 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.
The most common adverse reactions (all grades) observed in ≥2% (in those receiving DOVATO) were headache, diarrhea, nausea, insomnia, and fatigue.
- 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).
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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
3 Tivicay (dolutegravir) U.S. Approval 2013. Available at: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Tivicay/pdf/TIVICAY-PI-PIL.PDF#page=1. Accessed
4 Epivir (lamivudine) U.S. Approval 1995. Available at: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Epivir/pdf/EPIVIR-PI-PIL.PDF. Accessed
5 Dolutegravir plus lamivudine Prescribing Information. U.S. Approval
6 Dovato EU Summary of Product Characteristics.
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