ViiV Healthcare Submits Supplemental New Drug Application to US FDA for Use of Dovato in Virologically Suppressed Adults with HIV-1

Research Triangle Park, US, 16 October 2019 – ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer Inc. and Shionogi Limited as shareholders, announced the submission of a supplemental New Drug Application to the US Food and Drug Administration (FDA) for Dovato (dolutegravir and lamivudine) as a switch treatment for HIV-1 infection in virologically suppressed adults on a stable antiretroviral regimen with no treatment failure. In the US, Dovato is currently approved as a complete, once-daily, single-tablet regimen of dolutegravir (DTG) 50 mg and lamivudine (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.

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

Kimberly Smith, M.D., Head of Research & Development at ViiV Healthcare, said: “The TANGO study shows virologically suppressed adults with HIV-1 looking to switch their treatment can get the efficacy of a three-drug TAF-containing regimen with Dovato, a two-drug regimen. Today’s submission takes us a step closer toward offering this option for virologically suppressed adults living with HIV who are looking to treat HIV with fewer drugs.”

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 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 North America, Europe, Asia, Australia, 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.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 FDA approval.

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 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, 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 aim is 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.

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.

 

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References:

  1. Van Wyk, J. Switching to DTG+3TC fixed dose combination (FDC) is non-inferior to continuing a TAF-based regimen (TBR) in maintaining virologic suppression through 24 weeks (TANGO study). Presented at the 10th International AIDS Conference for HIV Science (IAS 2019), 21-24 July 2019, Mexico City, Mexico.
  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 2019.
  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 September 2019.
  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 September 2019.
  5. 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 September 2019.
  6. Dovato EU Summary of Product Characteristics. July 2019. Available at: https://www.medicines.org.uk/emc/product/10446/smpc. Accessed September 2019.    

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