Keypoints
- FDA Approves Low-Dose Tablet for HIV Treatment in Virologically Suppressed Children Weighing at Least 14 kg.
- Biktarvy Provides an Effective Treatment Option for a Diverse Range of People Living with HIV, including Children
- Biktarvy is a complete HIV-1 treatment that combines 3 powerful medicines to form the smallest 3-drug, integrase strand transfer inhibitor (INSTI)-based single-tablet regimen (STR).
- In February 2018, the US FDA approved Biktarvy (Bictegravir 50 mg/Emtricitabine 200 mg/Tenofovir Alafenamide 25 mg tablets, B/F/TAF) as a once-daily single-tablet regimen for the treatment of HIV-1 infection in adults.
- HIV medicine reduces the amount of HIV in the body (viral load) to a very low level, which keeps the immune system working and prevents illness. This is called viral suppression—defined as having less than 200 copies of HIV per milliliter of blood.
Gilead Sciences, Inc. announced the US Food and Drug Administration (FDA) approved a new low-dose tablet dosage form of Biktarvy.
Gilead Sciences, Inc. announced the US Food and Drug Administration (FDA) approved a new low-dose tablet dosage form of Biktarvy (Bictegravir 30 mg/Emtricitabine 120 mg/Tenofovir Alafenamide 15 mg tablets) for pediatric patients weighing at least 14 kg to less than 25 kg who are virologically suppressed or new to antiretroviral therapy. The approval of this supplemental New Drug Application (sNDA) expands the indication for Biktarvy to include younger children living with HIV-1 infection and will help to close the gap between HIV treatment options available for adults and children.
“Children living with HIV are in need of effective and accessible formulations of antiretroviral therapy,” said Merdad Parsey, MD, PhD, chief medical officer, Gilead Sciences. “To address this unmet need, innovations in pediatric formulations must strive towards expanding treatment options for children. The sNDA approval is an important step in fulfilling Gilead’s commitment to a goal of bringing pediatric formulations of Biktarvy to children living with HIV around the world.”
While effective available treatment options for pregnant women living with HIV lower the likelihood of perinatal HIV infection transmission, pediatric HIV remains a global health problem. Each day in 2020, approximately 850 children worldwide became infected with HIV and approximately 330 children died from AIDS-related causes, mostly because of inadequate access to HIV care and treatment services. The availability of a single-tablet antiretroviral regimen for children weighing at least 14 kg is a significant milestone with the potential to save many lives.
“As children living with HIV will be on therapy for the foreseeable future and from such a young age, there are a number of factors I weigh as a clinician when prescribing the right HIV treatment option to my pediatric patients,” said Carina Rodriguez, MD, Professor of Pediatrics and Division Chief of Pediatric Infectious Diseases at the University of South Florida Morsani College of Medicine. “Finding an efficacious treatment option is paramount, but tolerability and safety are keys to ensuring treatment success. With this expanded approval, clinicians can add Biktarvy to their arsenal of options to help ensure these children maintain virologic suppression with a treatment option that makes sense for them.”
In the United States, Biktarvy is indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 14 kg who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and no known substitutions associated with resistance to the individual components of Biktarvy. Biktarvy has a Boxed Warning for post treatment acute exacerbation of hepatitis B; please see below for additional Important Safety Information for Biktarvy.
The approval of Biktarvy for children weighing at least 14 kg is based on data from Cohort 3 of a phase 2/3 open-label, single-arm study (NCT02881320), which found Biktarvy low-dose tablets to be effective and generally well-tolerated through 24 weeks in virologically suppressed children living with HIV-1. Cohort 3 enrolled 22 participants weighing =14 to <25 kg who continued on treatment for 48 weeks and could then continue to receive study drug through an extension phase. After switching to Biktarvy, 91% (20/22) of participants remained virologically suppressed at Week 24, and the mean change in CD4 % from baseline was 0.2%. HIV-1 RNA was not collected at Week 24 for two participants because of Covid-19 pandemic-related study disruption. In pediatric studies, no new adverse reactions or laboratory abnormalities were identified compared to those observed in adults.
Biktarvy does not cure HIV or AIDS.
While there have been many advances in the treatment of HIV in children and adolescents, there still remains a need to prioritize, evaluate and develop options for the nearly 3 million children worldwide under the age of 19 living with HIV. An estimated 120,000 children and adolescents died from AIDS-related causes in 2020. About 72 percent of these mostly preventable deaths occurred among children under 10 years old. Newer, child-friendly formulations with appropriate dosing for children and adolescents represent an unmet need that is an important part of the considerations associated with long-term health and wellness for people who will live with HIV for their entire lives until we find a cure. Gilead has partnered with a number of global organizations and initiatives to ensure that we are optimizing and closing treatment gaps for children and adolescents in need so that ultimately, we can end the epidemic.
Biktarvy is a complete HIV-1 treatment that combines 3 powerful medicines to form the smallest 3-drug, integrase strand transfer inhibitor (INSTI)-based single-tablet regimen (STR) available, offering simple once-daily dosing with or without food, with a limited drug interaction potential and a high barrier to resistance. Biktarvy combines the novel, unboosted INSTI bictegravir, with the Descovy (emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, F/TAF) backbone. Biktarvy is a complete single-tablet regimen and should not be taken with other HIV-1 medicines.
About Biktarvy:
Bictegravir/Emtricitabine/tenofovir Alafenamide, sold under the brand name Biktarvy, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. One tablet, taken orally once daily, contains 50 mg Bictegravir, 200 mg Emtricitabine, and 25 mg Tenofovir Alafenamide. It was approved for use in the United States in February 2018, and for use in the European Union in June 2018.
Bictegravir/emtricitabine/tenofovir alafenamide Combination of:
Bictegravir(integrase inhibitor)
Emtricitabine (nucleoside reverse transcriptase inhibitor)
Tenofovir (alafenamide nucleotide reverse transcriptase inhibitor)
Biktarvy is a Combination therapy:
Bictegravir/EmtricitabineTtenofovir Alafenamide is an example of a combination drug that can be taken as a complete regimen for treatment of the human immunodeficiency virus.
Combination therapy for HIV, often called highly active antiretroviral therapy (HAART), is composed of two or more types of antiretroviral drugs. Combination therapy decreases the likelihood that drug resistance will occur, because it is unlikely that the HIV-1 strains will be able to mutate enough to become resistant to all drugs being used in the combination. Combination therapy increases the length of lives of patients with HIV-1, and can greatly reduce the possibility for transmission of the virus.
Components of biktarvy:
Bictegravir (BIC) is an integrase strand transfer inhibitor (INSTI). Bictegravir is different from other INSTIs because it contains a bridged bicyclic ring and a distinct benzyl tail with a 2,4,6-trifluorobenzyl group. This contributes to an increase in plasma protein binding and a reduction of activation of the pregnane X receptor (PXR). These changes minimize interactions between drugs, lower clearance, and increase solubility. Bictegravir was found to be less drug resistant than other drugs in the same class.
Emtricitabine (FTC) is a nucleoside reverse transcriptase inhibitor (NRTI) that is a synthetic fluoro derivative of thiacytidine. Within the cell, emtricitabine becomes phosphorylated, which forms emitricitabine 5′-triphosphate within the cell. This allows for the drug to compete with the viral and host substrate and ultimately causes a termination of DNA chain elongation. Underlying hepatitis B virus (HBV) can interact with emtricitabine to cause significant liver damage, but it does not have a significant detrimental effect on the liver when given to patients without HBV.
Tenofovir alafenamide (TAF) is a prodrug of tenofovir that functions as a nucleotide reverse transcriptase inhibitor (NRTI). Other prodrugs for tenofovir have been tested, but TAF is more efficient at refining HIV-1 therapy. It converts intracellularly to TFV diphosphate, which is a metabolite in HIV target cells. Thus, TAF has higher active metabolite concentrations and lower plasma TFV than other Tenovir prodrugs. TAF is metabolized primarily with the kidneys, and has a lower dosage than other prodrugs, so it is less detrimental to the renal elimination system.
Medical uses
This drug regimen is intended and approved for adults with HIV-1 infection who have had no previous antiretroviral treatment or for those with less than 50 copies of HIV-1 RNA per mL. Patients with HIV-1 should not have previously had any adverse reactions or resistance to bictegravir, emtricitabine, or tenofovir alafenamide.
Side effects
This drug should not be co-administered with dofetilide or rifampin. Dofetilide when taken with bictegravir/emtricitabine/tenofovir alafenamide can cause an increase in dofetilide plasma concentrations, which can lead to death. Rifampin and bictegravir/emtricitabine/tenofovir alafenamide when taken together can decrease bictegravir plasma concentrations and cause resistance to bictegravir/emtricitabine/tenofovir alafenamide. Other HIV-1 antiretroviral drugs should not be taken with this therapy.[citation needed]
If kidney disease or development of renal impairment is seen, the drug should be discontinued. Discontinuation of bictegravir/emtricitabine/tenofovir alafenamide in patients with hepatitis B and HIV-1 has been shown to increase the prevalence of hepatitis B, causing liver decompensation and liver failure.
Adverse drug reactions include, but are not limited to, diarrhea, nausea, and headache
When was Biktarvy get approval by FDA?
In February 2018, the US FDA approved Biktarvy (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) as a once-daily single-tablet regimen for the treatment of HIV-1 infection in adults. In June 2019, the FDA approved labeling revisions to Biktarvy, expanding the patient population to include pediatric patients weighing at least 25 kg. In October 2021, the FDA approved a new low-dose tablet formulation of Biktarvy (bictegravir 30 mg/emtricitabine 120 mg/tenofovir alafenamide 15 mg tablets) for pediatric patients weighing at least 14 kg to less than 25 kg. For all patient populations, Biktarvy is only indicated for the treatment of HIV-1 infection in people who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and no known substitutions associated with resistance to the individual components of Biktarvy.
About Gilead Sciences:
Gilead Sciences, Inc. is an American biopharmaceutical company headquartered in Foster City, California, that focuses on researching and developing antiviral drugs used in the treatment of HIV, hepatitis B, hepatitis C, and influenza, including Harvoni and Sovaldi. Gilead is a member of the NASDAQ Biotechnology Index and the S&P 500.
The company has been the subject of significant controversy over its business practices, including extremely high pricing of drugs such as Sovaldi and Truvada in the United States relative to production cost and cost in the developing world.
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