FDA Approves Dovato (dolutegravir/lamivudine) for HIV-1 Infection

In continuation of my update on Dolutegravir & Lamivudine

Dolutegravir (DTG)

Lamivudine, commonly called 3TC

ViiV Healthcare  announced the US Food and Drug Administration (FDA) approval of Dovato, 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 (ARV) treatment history and with no known resistance to either DTG or 3TC. Dovato, a two-drug regimen (2DR), reduces exposure to the number of ARVs from the start of treatment, while still maintaining the efficacy and high barrier to resistance of a traditional DTG-based three-drug regimen.

Deborah Waterhouse, CEO, ViiV Healthcare, said: “Building on our innovative portfolio of medicines, Dovato is powered by dolutegravir, an antiretroviral included in multiple combination therapies and the most prescribed integrase inhibitor in the world, 2 coupled with the established profile of lamivudine. With Dovato, the first complete, single-tablet, two-drug regimen for treatment-naïve adults, ViiV Healthcare is delivering what patients are requesting—a chance to treat their HIV-1 infection with as few drugs as possible, marking a significant step in HIV treatment.”

The approval of Dovato is supported by the landmark global GEMINI 1 and 2 studies that included more than 1,400 HIV-1 infected adults. In these studies, DTG + 3TC demonstrated non-inferiority based on plasma HIV-1 RNA <50 copies per milliliter (c/mL), a standard measure of HIV-1 control, at Week 48 when compared to a three-drug regimen of DTG and two nucleoside reverse transcriptase inhibitors (NRTIs), tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), in treatment-naïve, HIV-1 infected adults. The safety results for DTG + 3TC seen in GEMINI 1 and 2 were consistent with the product labelling for DTG and 3TC. No patient who experienced virologic failure in either treatment arm developed treatment-emergent resistance.

Pedro Cahn, principal investigator for the GEMINI study program said: “People are now living longer with HIV and will spend a lifetime taking drugs to suppress their virus. The approval of the fixed dose combination of dolutegravir and lamivudine, a complete, single-tablet, two-drug regimen, marks a pivotal moment in the treatment of HIV-1. Treatment-naïve people living with the virus have a powerful option that delivers non-inferior efficacy to a dolutegravir-based three-drug regimen, allowing them to take fewer ARVs and get and remain suppressed.”

Jeff Berry, Test Positive Aware Network (TPAN), said: “The approval of Dovato is a welcome paradigm shift, as it brings an innovative treatment approach to newly diagnosed adults with HIV-1. By exposing patients to fewer drugs at the start of treatment, the hope is to help address concerns arising from overall management of prolonged ARV therapy.”

DTG/3TC as a complete, once-daily, single-tablet, two-drug regimen for HIV-1 therapy is currently under review by the European Medicines Agency (EMA) and regulatory authorities in Canada, Australia, Switzerland, and South Africa and several additional submissions are planned throughout 2019.

About Dovato (dolutegravir/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 strand transfer inhibitor (INSTI) dolutegravir (Tivicay, 50 mg) with the nucleoside analogue reverse transcriptase inhibitor (NRTI) lamivudine (Epivir, 300 mg).

Like a DTG-based three-drug regimen, Dovato uses only two drugs to inhibit the viral cycle at two different sites. INSTIs, 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.

https://en.wikipedia.org/wiki/Dolutegravir
https://en.wikipedia.org/wiki/Lamivudine

FDA Approves Juluca, First Two-Drug Regimen for HIV Patients

In continuation of my updates on dolutegravir and rilpivirine,

The FDA has approved the first complete treatment regimen containing only two drugs to treat certain adults with human immunodeficiency virus type 1 (HIV-1) instead of the three or more drugs included in standard HIV treatment.

Juluca (dolutegravir/rilpivirine, ViiV Healthcare) is a fixed-dose tablet approved to treat adults with HIV-1 infections whose virus is currently suppressed (HIV-1 RNA less than 50 copies per mL) on a stable regimen for at least six months, with no history of treatment failure and no known substitutions associated with resistance to the individual components of the new combination. Dolutegravir 50 mg (ViiV Healthcare) is an integrase strand transfer inhibitor, and rilpivirine 25 mg (Janssen Therapeutics) is a non-nucleoside reverse transcriptase inhibitor.

 rilpivirine     Dolutegravir

 “Limiting the number of drugs in any HIV treatment regimen can help reduce toxicity for patients,” said Debra Birnkrant, MD, director of the Division of Antiviral Products in the FDA’s Center for Drug Evaluation and Research.

HIV weakens a person’s immune system by destroying important cells that fight disease and infection. According to the Centers for Disease Control and Prevention, an estimated 1.1 million people in the United States are living with HIV, and the disease remains a significant cause of death for certain populations.

This FDA approval is based primarily on data from two pivotal phase 3 clinical trials, SWORD-12 and SWORD-2,2 which showed the two-drug regimen achieved non-inferior viral suppression (HIV-1 RNA less than 50 copies per mL) at 48 weeks compared with patients’ three- or four-drug current antiretroviral regimen (CAR) in both pooled and individual analyses of the SWORD-1 and SWORD-2 studies (dolutegravir/rilpivirine 486/513 [95%], CAR 485/511 [95%]; adjusted difference, –0.2%; 95% confidence interval, –3.0% to  2.5%, pooled analysis). Virological suppression rates were similar between treatment arms. Drug related adverse events and adverse events leading to withdrawal occurred in low frequencies in both arms of the study, but more frequently in the investigational arm.

The most common side effects in patients taking Juluca were diarrhea and headache. Serious side effects include skin rash and allergic reactions, liver problems, and depression or mood changes. Juluca should not be given with other anti-HIV drugs and may have drug interactions with other commonly used medications.

Ref : https://www.viivhealthcare.com/media/press-releases/2017/november/viiv-healthcare-announces-us-fda-approval-for-juluca.aspx

FDA Approves Juluca, First Two-Drug Regimen for HIV Patients

FDA Approves Juluca (dolutegravir and rilpivirine) for the Maintenance Treatment of Virologically Suppressed HIV-1 Infection

In continuation of my update on dolutegravir  and rilpivirine

The U.S. Food and Drug Administration today approved Juluca, the first complete treatment regimen containing only two drugs to treat certain adults with human immunodeficiency virus type 1 (HIV-1) instead of three or more drugs included in standard HIV treatment. Juluca is a fixed-dose tablet containing two previously approved drugs (dolutegravir and rilpivirine) to treat adults with HIV-1 infections whose virus is currently suppressed on a stable regimen for at least six months, with no history of treatment failure and no known substitutions associated with resistance to the individual components of Juluca.

“Limiting the number of drugs in any HIV treatment regimen can help reduce toxicity for patients,” said Debra Birnkrant, M.D., director of the Division of Antiviral Products in the FDA’s Center for Drug Evaluation and Research.

HIV weakens a person’s immune system by destroying important cells that fight disease and infection. According to the Centers for Disease Control and Prevention, an estimated 1.1 million people in the United States are living with HIV, and the disease remains a significant cause of death for certain populations.

Juluca’s safety and efficacy in adults were evaluated in two clinical trials of 1,024 participants whose virus was suppressed on their current anti-HIV drugs. Participants were randomly assigned to continue their current anti-HIV drugs or to switch to Juluca. Results showed Juluca was effective in keeping the virus suppressed and comparable to those who continued their current anti-HIV drugs.

The most common side effects in patients taking Juluca were diarrhea and headache. Serious side effects include skin rash and allergic reactions, liver problems and depression or mood changes. Juluca should not be given with other anti-HIV drugs and may have drug interactions with other commonly used medications.

Ref : https://en.wikipedia.org/wiki/Dolutegravir

https://en.wikipedia.org/wiki/Rilpivirine

FDA Approves Juluca (dolutegravir and rilpivirine) for the Maintenance Treatment of Virologically Suppressed HIV-1 Infection

FDA Approves Triumeq for the Treatment of HIV-1 Infection

In continuation of my update on Triumeq

ViiV Healthcare announced today that the U.S. Food and Drug Administration (FDA) has approved Triumeq (abacavir 600mg, dolutegravir 50mg and lamivudine 300mg) tablets for the treatment of HIV-1 infection. Triumeq is ViiV Healthcare’s first dolutegravir-based fixed-dose combination, offering many people living with HIV the option of a single-pill regimen that combines the integrase strand transfer inhibitor (INSTI) dolutegravir, with the nucleoside reverse transcriptase inhibitors (NRTIs) abacavir and lamivudine.

FDA Approves Triumeq for the Treatment of HIV-1 Infection

FDA Approves Triumeq for the Treatment of HIV-1 Infection

ViiV Healthcare announced today that the U.S. Food and Drug Administration (FDA) has approved Triumeq (abacavir 600mg (below-Ist), dolutegravir (below -IInd) 50mg and lamivudine (below IIIrd respectively) 300mg) tablets for the treatment of HIV-1 infection.  Triumeq is ViiV Healthcare’s first dolutegravir-based fixed-dose combination, offering many people living with HIV the option of a single-pill regimen that combines the integrase strand transfer inhibitor (INSTI) dolutegravir, with the nucleoside reverse transcriptase inhibitors (NRTIs) abacavir and lamivudine.

FDA Approves Triumeq for the Treatment of HIV-1 Infection

Long-acting drug effectively prevents HIV-like infection in monkeys

Cabotegravir (USAN  and INN ) (also known as S/GSK1265744 or previously referred to by the research code GSK744) is an investigational new drug under development for the treatment of HIV infection. It is an integrase inhibitor, with a carbamoyl pyridone structure similar to dolutegravir. In investigational studies, the agent has been packaged intonanoparticles (GSK744LAP) conferring an exceptionally long half-life of 21–50 days following a single dose. In theory, this would make possible suppression of HIV with dosing as infrequently as once every three months.

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HIV researchers hope a new compound, known as cabotegravir, could make dosing easier for some because the drug would be administered by injection once every three months. A clinical trial testing long-acting cabotegravir's safety and acceptability has already begun at multiple U.S. sites including The Rockefeller University Hospital. Meanwhile two new studies, including one conducted by researchers at the Aaron Diamond AIDS Research Center (ADARC) and Rockefeller University, published today (January 15) inScience Translational Medicine, show that long-acting cabotegravir injections are highly protective in a monkey model of vaginal transmission of a virus similar to HIV.

"Clinical trial results have demonstrated that the effectiveness of preventive oral medications can range with results as high as 75 percent effective to as low as ineffective, and a lot of that variability appears to hinge on the patient's ability to take the pills as prescribed," says study researcher Martin
Markowitz, a professor at Rockefeller University and ADARC. "Long acting cabotegravir has the potential to create an option that could improve adherence by making it possible to receive the drug by injection once every three months."

Developed by ViiV Healthcare and GlaxoSmithKline, and previously known as GSK744 LA, cabotegravir is an antiretroviral drug. Antiretrovirals interfere with HIV's ability to replicate itself using a host cell and they are used to treat an HIV infection or to prevent those at high risk from acquiring it in the first place.

Long-acting drug effectively prevents HIV-like infection in monkeys