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Trade names | Sunlenca |
Other names | GS-CA1, GS-6207 |
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Routes of administration | By mouth, subcutaneous |
Drug class | Capsid inhibitors |
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Formula | C39H32ClF10N7O5S2 |
Molar mass | 968.28 g·mol−1 |
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Lenacapavir, sold under the brand name Sunlenca, is an antiretroviral medication used to treat HIV/AIDS. [9] [10] It is taken by mouth or by subcutaneous injection. [9] [10]
The most common side effects include reactions at the injection site and nausea. [10] [11]
Lenacapavir was approved for medical treatment in the European Union in August 2022, [10] [12] in Canada in November 2022, [5] [6] and in the United States in December 2022. [9] [11] [13] [14] It is the first of a class of drugs called capsid inhibitors to be approved by the US Food and Drug Administration (FDA) for treating HIV/AIDS. [11] [15]
Lenacapavir, in combination with other antiretrovirals, is indicated for the treatment of HIV/AIDS. [9] It is used in heavily treatment-experienced adults with multiple drug resistance in whom current antiretroviral therapy is ineffective due to resistance, intolerance or safety considerations. [9] [11]
Lenacapavir works by binding directly to the interface between HIV-1 viral capsid protein (p24) subunits in capsid hexamers, interfering with essential steps of viral replication, including capsid-mediated nuclear uptake of HIV-1 proviral DNA, virus assembly and release, production of capsid protein subunits, and capsid core formation. [9] [11] The US Food and Drug Administration considers it to be a first-in-class medication. [15] [16]
Lenacapavir was developed by Gilead Sciences. [17]
The safety and efficacy of lenacapavir were established through a multicenter clinical trial with 72 participants whose HIV infections were resistant to multiple classes of HIV medications. [11] These participants had to have high levels of virus in their blood despite being on antiretroviral drugs. [11] Participants were enrolled into one of two study groups. [11] One group was randomized to receive either lenacapavir or placebo in a double-blind fashion, and the other group received open-label lenacapavir. [11] The primary measure of efficacy was the proportion of participants in the randomized study group who achieved a certain level of reduction in virus during the initial 14 days compared to baseline. [11]
The U.S. Food and Drug Administration granted the application for lenacapavir priority review, fast track, and breakthrough therapy designations. [11]
In June 2022, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Sunlenca, intended for the treatment of adults with multidrug‑resistant human immunodeficiency virus type 1 (HIV‑1) infection. [18] The applicant for this medicinal product is Gilead Sciences Ireland UC. [18]
Lenacapavir was approved for medical use in the European Union in August 2022, [10] [19] in Canada in November 2022, [5] [6] and in the United States in December 2022. [11]
As of 2024 [update] the drug, produced by Gilead, costs US$42,250 for the first year. A study presented in July 2024 [20] found that mass production of a generic version would allow a profit margin of 30% on an annual price of $40 if used by 10 million people. The authors said that lowering HIV levels significantly would probably require 60 million people to take the drug preventatively. [21]
As of 2021, it is in phase II/III clinical trials. [22] It is being investigated as a treatment for HIV patients infected with multidrug-resistant virus and as a twice-yearly injectable for pre-exposure prophylaxis. [22] [23]
Studies have been conducted for the use of lenacapavir in treatment-naive individuals. [24] For virally suppressed individuals switching treatment, early studies have tested lenacapavir injections in combination with infusions of the broadly neutralizing antibodies teropavimab and zinlirvimab [25] as well as lenacapavir with islatravir. [26]
Published results [27] [28] presented at a July 2024 conference [29] [30] showed 100% efficacy of Lenacapavir for HIV prevention from a randomized phase 3 clinical trial of 5000 patients for those who received the drug.
Enfuvirtide (INN), sold under the brand name Fuzeon, is an HIV fusion inhibitor, the first of a class of antiretroviral drugs used in combination therapy for the treatment of AIDS/HIV.
Protease inhibitors (PIs) are medications that act by interfering with enzymes that cleave proteins. Some of the most well known are antiviral drugs widely used to treat HIV/AIDS, hepatitis C and COVID-19. These protease inhibitors prevent viral replication by selectively binding to viral proteases and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles.
Emtricitabine/tenofovir, sold under the brand name Truvada among others, is a fixed-dose combination antiretroviral medication used to treat and prevent HIV/AIDS. It contains the antiretroviral medications emtricitabine and tenofovir disoproxil. For treatment, it must be used in combination with other antiretroviral medications. For prevention before exposure, in those who are at high risk, it is recommended along with safer sex practices. It does not cure HIV/AIDS. Emtricitabine/tenofovir is taken by mouth.
Pre-exposure prophylaxis for HIV prevention, commonly known as PrEP, is a form of medication used to prevent HIV infection, the cause of HIV/AIDS.
Darunavir (DRV), sold under the brand name Prezista among others, is an antiretroviral medication used to treat and prevent HIV/AIDS. It is generally recommended for use with other antiretrovirals. It is often used with low doses of ritonavir or cobicistat to increase darunavir levels. It may be used for prevention after a needlestick injury or other potential exposure. It is taken by mouth once to twice a day.
Efavirenz/emtricitabine/tenofovir, sold under the brand name Atripla among others, is a fixed-dose combination antiretroviral medication used to treat HIV/AIDS. It contains efavirenz, emtricitabine, and tenofovir disoproxil. It can be used by itself or together with other antiretroviral medications. It is taken by mouth.
Integrase inhibitors (INIs) are a class of antiretroviral drug designed to block the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell. Since integration is a vital step in retroviral replication, blocking it can halt further spread of the virus. Integrase inhibitors were initially developed for the treatment of HIV infection, but have been applied to other retroviruses. The class of integrase inhibitors called integrase strand transfer inhibitors (INSTIs) are in established medical use. Other classes, such as allosteric integrase inhibitors (ALLINIs) or integrase binding inhibitors (INBIs), are still experimental.
Ibalizumab, sold under the brand name Trogarzo, is a non-immunosuppressive humanised monoclonal antibody that binds CD4, the primary receptor for HIV, and inhibits HIV from entering cells. It is a post-attachment inhibitor, blocking HIV from binding to the CCR5 and CXCR4 co-receptors after HIV binds to the CD4 receptor on the surface of a CD4 cell. Post-attachment inhibitors are a subclass of HIV drugs called entry inhibitors.
Elvitegravir (EVG) is an integrase inhibitor used to treat HIV infection. It was developed by the pharmaceutical company Gilead Sciences, which licensed EVG from Japan Tobacco in March 2008. The drug gained approval by the U.S. Food and Drug Administration on August 27, 2012, for use in adult patients starting HIV treatment for the first time as part of the fixed dose combination known as Stribild. On September 24, 2014, the FDA approved Elvitegravir as a single pill formulation under the trade name Vitekta. On November 5, 2015, the FDA approved the drug for use in patients affected with HIV-1 as a part of a second fixed dose combination pill known as Genvoya.
Rilpivirine, sold under the brand names Edurant and Rekambys, is a medication, developed by Tibotec, used for the treatment of HIV/AIDS. It is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with higher potency, longer half-life and reduced side-effect profile compared with older NNRTIs such as efavirenz.
Emtricitabine/rilpivirine/tenofovir, sold under the brand name Complera among others, is a fixed-dose combination of antiretroviral drugs for the treatment of HIV/AIDS. The drug was co-developed by Gilead Sciences and Johnson & Johnson's Tibotec division and was approved by the US Food and Drug Administration (FDA) in August 2011, and by the European Medicines Agency in November 2011, for patients who have not previously been treated for HIV. It is available as a once-a-day single tablet.
Elvitegravir/cobicistat/emtricitabine/tenofovir, sold under the brand name Stribild, also known as the Quadpill, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. Elvitegravir, emtricitabine and tenofovir disoproxil directly suppress viral reproduction. Cobicistat increases the effectiveness of the combination by inhibiting the liver and gut wall enzymes that metabolize elvitegravir. It is taken by mouth. It is manufactured by Gilead Sciences.
Cabotegravir, sold under the brand name Vocabria among others, is a antiretroviral medication used for the treatment of HIV/AIDS. It is available in the form of tablets and as an intramuscular injection, as well as in an injectable combination with rilpivirine under the brand name Cabenuva.
Fostemsavir, sold under the brand name Rukobia, is an antiretroviral medication for adults living with HIV/AIDS who have tried multiple HIV medications and whose HIV infection cannot be successfully treated with other therapies because of resistance, intolerance or safety considerations.
Islatravir is an investigational drug for the treatment of HIV infection. It is classified as a nucleoside reverse transcriptase translocation inhibitor (NRTTI). Merck is developing a subdermal drug-eluting implant to administer islatravir.
Bictegravir is a second-generation integrase inhibitor (INSTI) class that was structurally derived from an earlier compound dolutegravir by scientists at Gilead Sciences. In vitro and clinical results were presented by Gilead in the summer of 2016. In 2016, bictegravir was in a Phase 3 trial as part of a single tablet regimen in combination with tenofovir alafenamide (TAF) and emtricitabine (FTC) for the treatment of HIV-1 infection.
Bictegravir/emtricitabine/tenofovir alafenamide, sold under the brand name Biktarvy, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. It contains bictegravir, a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor; emtricitabine, an HIV-1 nucleoside analog reverse transcriptase inhibitor; and tenofovir alafenamide, an HIV-1 nucleoside analog reverse transcriptase inhibitor.
Dolutegravir/lamivudine, sold under the brand name Dovato, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. each pill contains 50 mg dolutegravir, as the salt, an integrase strand transfer inhibitor (INSTI), and 300 mg lamivudine, a nucleoside analogue reverse transcriptase inhibitor (NRTI). It is taken by mouth.
Cabotegravir/rilpivirine, sold under the brand name Cabenuva, is a co-packaged antiretroviral medication for the treatment of HIV/AIDS. It contains cabotegravir and rilpivirine in a package with two separate injection vials.
In the management of HIV/AIDS, HIV capsid inhibitors are antiretroviral medicines that target the capsid shell of the virus. This is in contrast to most current antiretroviral drugs used to treat HIV, which do not directly target the viral capsid. These have also been termed "Capsid-targeting Antivirals", "Capsid Effectors", and "Capsid Assembly Modulators (CAMs)". Because of this, drugs that specifically inhibit the HIV capsid are being developed in order to reduce the replication of HIV, and treat infections that have become resistant to current antiretroviral therapies.