Search

EP-3852761-B1 - AN ADMINISTRATION REGIMEN OF INTEGRASE INHIBITORS FOR PREVENTING HIV INFECTION BY POST-EXPOSURE PROPHYLAXIS

EP3852761B1EP 3852761 B1EP3852761 B1EP 3852761B1EP-3852761-B1

Inventors

  • BEKERMAN, Elena
  • CALLEBAUT, CHRISTIAN
  • MCCALLISTER, SCOTT

Dates

Publication Date
20260513
Application Date
20190918

Claims (13)

  1. Bictegravir, or a pharmaceutically acceptable salt thereof, emtricitabine, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide, or a pharmaceutically acceptable salt thereof, for use in a method of preventing an HIV infection in a subject by post-exposure prophylaxis, the method comprising a first administration within or at 24 hours after exposure of the subject to the HIV, and a second administration within or at 24 hours after the first administration, of the bictegravir, or a pharmaceutically acceptable salt thereof, emtricitabine, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide, or a pharmaceutically acceptable salt thereof, wherein, in each of the first and second administrations, the bictegravir, or a pharmaceutically acceptable salt thereof, is administered in a dosage of 50 mg or 100 mg, the emtricitabine, or a pharmaceutically acceptable salt thereof, is administered in a dosage of 200 mg and the tenofovir alafenamide, or a pharmaceutically acceptable salt thereof, is administered in a dosage of 25 mg.
  2. The bictegravir, or a pharmaceutically acceptable salt thereof, emtricitabine, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide, or a pharmaceutically acceptable salt thereof, for use of claim 1, wherein the method comprises: i) a first administration at 6 hours after exposure of the subject to the HIV; and ii) a second administration at 30 hours after exposure of the subject to the HIV.
  3. The bictegravir, or a pharmaceutically acceptable salt thereof, emtricitabine, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide, or a pharmaceutically acceptable salt thereof, for use of claim 1, wherein the method comprises: i) a first administration at 12 hours after exposure of the subject to the HIV; and ii) a second administration at 36 hours after exposure of the subject to the HIV.
  4. The bictegravir, or a pharmaceutically acceptable salt thereof, emtricitabine, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide, or a pharmaceutically acceptable salt thereof, for use of claim 1, wherein the method comprises: i) a first administration at 24 hours after exposure of the subject to the HIV; and ii) a second administration at 48 hours after exposure of the subject to the HIV.
  5. The bictegravir, or a pharmaceutically acceptable salt thereof, emtricitabine, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide, or a pharmaceutically acceptable salt thereof, for use of any preceding claim, wherein the bictegravir, or a pharmaceutically acceptable salt thereof, emtricitabine, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide, or a pharmaceutically acceptable salt thereof are administered: (i) simultaneously; (ii) as a unitary dosage form; and/or (iii) as a fixed dose combination tablet.
  6. The bictegravir, or a pharmaceutically acceptable salt thereof, emtricitabine, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide, or a pharmaceutically acceptable salt thereof, for use of any one of the preceding claims, wherein the tenofovir alafenamide, or a pharmaceutically acceptable salt thereof is tenofovir alafenamide hemifumarate.
  7. The bictegravir, or a pharmaceutically acceptable salt thereof, emtricitabine, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide, or a pharmaceutically acceptable salt thereof, for use of any one of the preceding claims, wherein the emtricitabine, or a pharmaceutically acceptable salt thereof is emtricitabine.
  8. The bictegravir, or a pharmaceutically acceptable salt thereof, emtricitabine, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide, or a pharmaceutically acceptable salt thereof, for use of any one of the preceding claims, wherein the bictegravir, or a pharmaceutically acceptable salt thereof, emtricitabine, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide, or a pharmaceutically acceptable salt thereof, are administered orally.
  9. The bictegravir, or a pharmaceutically acceptable salt thereof, emtricitabine, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide, or a pharmaceutically acceptable salt thereof, for use of any one of the preceding claims, wherein the bictegravir, or a pharmaceutically acceptable salt thereof, emtricitabine, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide, or a pharmaceutically acceptable salt thereof, are administered parenterally, optionally wherein the parenteral administration is selected from sub-cutaneous administration, intramuscular administration, transdermal administration, and vaginal administration.
  10. The bictegravir, or a pharmaceutically acceptable salt thereof, emtricitabine, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide, or a pharmaceutically acceptable salt thereof, for use of any one of the preceding claims, wherein the bictegravir, or a pharmaceutically acceptable salt thereof, is administered to the subject through a medical device, optionally wherein the medical device is selected from a patch, an implantable device, a syringe, and a contraceptive device.
  11. The bictegravir, or a pharmaceutically acceptable salt thereof, emtricitabine, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide, or a pharmaceutically acceptable salt thereof, for use of any one of the preceding claims, wherein the bictegravir is administered as bictegravir sodium.
  12. The bictegravir, or a pharmaceutically acceptable salt thereof, emtricitabine, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide, or a pharmaceutically acceptable salt thereof, for use of any one of the preceding claims, wherein the subject has been identified as an individual who is at risk of sexual transmission of HIV.
  13. The bictegravir, or a pharmaceutically acceptable salt thereof, emtricitabine, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide, or a pharmaceutically acceptable salt thereof, for use of any one of the preceding claims, wherein the HIV is: (i) HIV-1; or (ii) HIV-2.

Description

FIELD The present disclosure relates to bictegravir, or a pharmaceutically acceptable salt thereof, emtricitabine, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide, or a pharmaceutically acceptable salt thereof, for use in methods of preventing HIV in a subject. BACKGROUND The HIV/AIDS pandemic has claimed the lives of millions of people, and millions more are currently infected. Antiretroviral therapy has turned HIV infection into a chronic, manageable disease; however, no cure yet exists for HIV. Reduction in the number of new HIV infections is a global goal. To this end, prevention regimens relating to both pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) are being explored. Truvada (emtricitabine-tenofovir) is currently the only medication approved for PrEP. Accordingly, new and effective means for preventing HIV infection are needed and the methods described herein are developed to help meet this need. US2015366872A1 relates to crystalline forms and co-crystals of (2R,5S,13aR)-8-hydroxy-7,9-dioxo-N-(2,4,6-trifluorobenzyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide, the pharmaceutical formulations, and the therapeutic uses thereof. WO2015196116A1 relates to sodium (2R,5S,13aR)-7,9-dioxo-10 -((2,4,6-trifluorobenzyl)carbamoyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1',2':4,5] pyrazino[2,1-b][1,3]oxazepin-8-olate Form I. David Wohl et al. (2018) relates to patient-reported symptoms over 48 weeks among participants in Phase III non-inferiority trials of adults with HIV on co-formulated bictegravir, emtricitabine and tenofovir alafenamide versus co-formulated abacavir, dolutegravir and lamivudine. Conference report for NATAP, IAS 2017: Conference on HIV Pathogenesis Treatment and Prevention (anonymous) relates to Gilead's announcement of Phase 3 results for the investigational fixed-dose combination of bictegravir, emtricitabine and tenofovir alafenamide for treatment of HIV. Anthony Markham (2018) relates to the development of bictegravir leading to the first approval of bictegravir/emtricitabine/tenofovir alafenamide as treatment for HIV-1 infection Mayer Kenneth et al. (2017) relates to HIV postexposure prophylaxis regimen completion with single tablet daily elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine compared with more frequent dosing regimens. SUMMARY The present invention is defined in the appended claims, and it provides bictegravir, or a pharmaceutically acceptable salt thereof, emtricitabine, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide, or a pharmaceutically acceptable salt thereof, for use in a method of preventing an HIV infection in a subject by post-exposure prophylaxis, the method comprising a first administration within or at 24 hours after exposure of the subject to the HIV, and a second administration within or at 24 hours after the first administration, of the bictegravir, or a pharmaceutically acceptable salt thereof, emtricitabine, or a pharmaceutically acceptable salt thereof, and tenofovir alafenamide, or a pharmaceutically acceptable salt thereof, wherein, in each of the first and second administrations, the bictegravir, or a pharmaceutically acceptable salt thereof, is administered in a dosage of 50 mg or 100 mg, the emtricitabine, or a pharmaceutically acceptable salt thereof, is administered in a dosage of 200 mg and the tenofovir alafenamide, or a pharmaceutically acceptable salt thereof, is administered in a dosage of 25 mg.. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows a representative scheme illustrating the event driven study design of Example 5.FIG. 2 shows a PrEP/PEP study design schematic further described in Example 6.FIG. 3 shows survival in the PrEP/PEP study animals as a percent of SHIV-negative animals per group following eight cycles of low-dose rectal challenge (see Example 6).FIG. 4 shows a PEP study design schematic further described in Example 6.FIG. 5 shows survival in the PEP study animals as a percent of SHIV-negative animals per group following five rectal challenge (see Example 6). DETAILED DESCRIPTION In some embodiments, the bictegravir is administered as bictegravir sodium. In some embodiments, the subject may have or be at risk of having the infection. In some embodiments, the subject has been identified as an individual who is at risk of sexual transmission of HIV. In some embodiments, the individual has been identified as a man, transgender man, transgender woman, or woman who has sex with men, a heterosexual men, a heterosexual woman, and or a sex worker. In some embodiments, the individual has been identified as: having anal sex with at least two different sexual partners and no consistent condom use over the last 6 months; and/orhaving history of sexually transmitted diseases (STDs) during the last 12 months (e.g., syphilis, gonorrhea, chlamydiae, HBV or HCV infection); and/orusing psycho-