BIKTARVY Prescribing Information DESCOVY Prescribing Information Important Safety
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Treatment-Naïve Adults Overview Study Design Efficacy Resistance

INDICATION

BIKTARVY® is indicated as a complete regimen for the treatment of HIV-1 infection in adults who have no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA <50 copies per mL) on a stable ARV regimen for ≥3 months with no history of treatment failure and no known resistance to any component of BIKTARVY.

DHHS RECOMMENDED
AS AN INITIAL REGIMEN FOR
ADULTS WITH HIV-11

BIKTARVY® is Backed by Robust Clinical Trial Experience1-4,6-8

BIKTARVY was approved based on data from four phase 3 clinical trials, including more than 1200 patients

Treatment-Naïve Adults

STUDY 1489

BIKTARVY (n=314)
vs
ABC/DTG/3TC
(n=315)

STUDY 1490

BIKTARVY (n=320)
vs
FTC/TAF+DTG
(n=325)

Virologically Suppressed Adults

STUDY 1844

Switched to BIKTARVY (n=282) or continued on ABC/DTG/3TC (n=281)

STUDY 1878

Switched to BIKTARVY (n=290) or stayed on baseline regimen* (n=287)


BIKTARVY was studied in an additional phase 3 clinical trial comprised of adult women

Virologically Suppressed Adult Women

STUDY 1961

Switched to BIKTARVY (n=234) or
stayed on baseline regimen† (n=236)

BIKTARVY has an extensive clinical trial program with studies in a broad range of patients, including those of various age groups and ethnicities


IMPORTANT SAFETY INFORMATION

BOXED WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B

  • Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of BIKTARVY. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue BIKTARVY. If appropriate, anti-hepatitis B therapy may be warranted.

BIKTARVY vs ABC/DTG/3TC in Treatment-Naïve Adults1,3


Study 1489: Phase 3, Randomized, Double-Blind, Active-Controlled Study

Treatment-Naïve Adults
(N=629)
  • HIV-1 RNA ≥500 copies/mL
  • eGFRCG ≥50 mL/min

1:1

BIKTARVY QD
(n=314)

ABC/DTG/3TC QD
(n=315)

Week 48
Primary endpoint

Primary endpoint

Proportion of adults with HIV-1 RNA <50 copies/mL at Week 48 using the FDA snapshot algorithm

Baseline Characteristics
Study 14893:
Selected Baseline Characteristics		 BIKTARVY®(n=314) ABC/
DTG/3TC(n=315)
Median age, years (range) 31(18-71) 32(18-68)
Sex
Male, % 91 90
Female, % 9 10
Race/Ethnicity
White, % 57 57
Black, % 36 36
Hispanic/Latino, % 23 21
Asian, % 2 3
Median HIV-1 RNA, log10 copies/mL (IQR) 4.42(4.03-4.87) 4.51(4.04-4.87)
HIV-RNA >100,000 copies/mL, % 17 16
Median CD4+ cell count, cells/μL (IQR) 443(299-590) 450(324-608)
CD4+ count <200 cells/μL, % 11 10
Asymptomatic HIV infection, % 91 91
Median creatinine clearance, mL/min (IQR) 125.9(107.7-146.3) 123.0(107.0-144.3)

IMPORTANT SAFETY INFORMATION

Contraindications

  • Coadministration: Do not use BIKTARVY with dofetilide or rifampin.

IQR, interquartile range.



BIKTARVY vs FTC/TAF+DTG in Treatment-Naïve Adults1,4


Study 1490: Phase 3, Randomized, Double-Blind, Active-Controlled Study

Treatment-Naïve Adults
(N=645)
  • HIV-1 RNA ≥500 copies/mL
  • eGFRCG ≥30 mL/min

1:1

BIKTARVY QD
(n=320)

FTC/TAF+DTG QD
(n=325)

Week 48
Primary endpoint

Primary endpoint

Proportion of adults with HIV-1 RNA <50 copies/mL at Week 48 using the FDA snapshot algorithm

Baseline Characteristics
Study 14904:
Selected Baseline Characteristics		 BIKTARVY®(n=320) FTC/TAF
+DTG(n=325)
Median age, years (range) 33(18-71) 34(18-77)
Sex
Male, % 88 89
Female, % 12 11
Race/Ethnicity
White, % 57 60
Black, % 30 31
Hispanic/Latino, % 26 25
Asian, % 2 3
Median HIV-1 RNA, log10 copies/mL (IQR) 4.43(3.95-4.90) 4.45(4.03-4.84)
HIV-RNA >100,000 copies/mL, % 21 17
Median CD4+ cell count, cells/μL (IQR) 440(289-591) 441(297-597)
CD4+ count <200 cells/μL, % 14 10
Asymptomatic HIV infection, % 89 89
Median creatinine clearance, mL/min (IQR) 120.4(100.8-141.8) 120.6(102.8-145.1)

IMPORTANT SAFETY INFORMATION

Contraindications

  • Coadministration: Do not use BIKTARVY with dofetilide or rifampin.

IQR, interquartile range.


IMPORTANT SAFETY INFORMATION (cont'd)

Contraindications

  • Coadministration: Do not use BIKTARVY with dofetilide or rifampin.

Powerful Efficacy in Treatment-Naïve Adults1-5

Results noninferior to comparators at Week 48


Virologic Response


Virologic Response in Study 1489 and Study 1490

Study 1489

‡95% confidence interval.


Study 1490

‡95% confidence interval.


  • Treatment outcomes were similar across subgroups, regardless of age, sex, race, baseline viral load, and baseline CD4+ cell count1
  • Adults with HIV-1 RNA ≥50 copies/mL include those who were not virologically suppressed at Week 48, and those who were not virologically suppressed when they discontinued early due to lack/loss of efficacy, or reasons other than AEs, death, or lack/loss of efficacy1
  • In Study 1489, 0 adults in either group had missing post-baseline virologic data2
  • In Study 1490, 6 adults in the BIKTARVY group and 0 adults in the FTC/TAF+DTG group had missing post-baseline virologic data5
M=F Analysis

Overall Rapid Reduction in Viral Load With BIKTARVY®2-4

Missing=Failure Analysis (M=F)


Missing=Failure Analysis (M=F) for Study 1489 Missing=Failure Analysis (M=F) for Study 1490

Studies 1489 and 1490 primary endpoints

Proportion of adults with HIV-1 RNA <50 copies/mL at Week 48 using the FDA snapshot algorithm


  • The M=F analysis was an additional prespecified endpoint of the studies. Results of the M=F analyses were consistent with the primary endpoint

IMPORTANT SAFETY INFORMATION

Adverse reactions

  • Most common adverse reactions (incidence ≥5%; all grades) in clinical studies were diarrhea (6%), nausea (5%), and headache (5%).

No Treatment-Emergent Resistance Associated With BIKTARVY1,3,4

In two large phase 3 clinical trials in treatment-naïve adults through Week 48

0
cases of resistance with
BIKTARVY
  • Among 634 treatment-naïve adults in Studies 1489 and 1490, 8 treatment-failure subjects were tested and no amino acid substitutions emerged that were associated with BIKTARVY resistance
Virologic Outcomes
Study 1489:
Virologic Outcomes at Week 481*

Study 1489

BIKTARVY®(n=314)
ABC/
DTG/
3TC(n=315)

Study 1490

BIKTARVY(n=320)
FTC/TAF
+DTG(n=325)
HIV-1 RNA <50 copies/mL 92% 93% 89% 93%
Treatment difference (95% CI) BIKTARVY vs comparator -0.6%(-4.8% to 3.6%) -3.5%(-7.9% to 1.0%)
HIV-1 RNA ≥50 copies/mL† 1% 3% 4% 1%
No virologic data at Week 48 window 7% 4% 6% 6%
Discontinued study drug due to AE or death‡ 0% 1% 1% 1%
Discontinued study drug due to other reasons and last available HIV-1 RNA <50 copies/mL§ 5% 3% 3% 4%
Missing data during window but on study drug 2% <1%   2% 1%
Study 1490:
Virologic Outcomes at Week 481*

BIKTARVY(n=320)
FTC/TAF
+DTG(n=325)
HIV-1 RNA <50 copies/mL 89% 93%
Treatment difference (95% CI) BIKTARVY vs comparator -3.5%(-7.9% to 1.0%)
HIV-1 RNA ≥50 copies/mL† 4% 1%
No virologic data at Week 48 window 6% 6%
Discontinued study drug due to AE or death‡ 1% 1%
Discontinued study drug due to other reasons and last available HIV-1 RNA <50 copies/mL§ 3% 4%
Missing data during window but on study drug 2% 1%

*Week 48 window was between Day 295 and 378 (inclusive).

†Includes subjects who had ≥50 copies/mL in the Week 48 window; subjects who discontinued early due to lack or loss of efficacy; and subjects who discontinued for reasons other than an adverse event (AE), death, or lack or loss of efficacy and at the time of discontinuation had a viral value of ≥50 copies/mL.

‡Includes subjects who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted in no virologic data on treatment during the specified window.

§Includes subjects who discontinued for reasons other than an AE, death, or lack or loss of efficacy, eg, withdrew consent, loss to follow-up, etc.

IMPORTANT SAFETY INFORMATION

Adverse reactions

  • Most common adverse reactions (incidence ≥5%; all grades) in clinical studies were diarrhea (6%), nausea (5%), and headache (5%).

CI, confidence interval.


INDICATION

BIKTARVY® is indicated as a complete regimen for the treatment of HIV-1 infection in adults who have no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA <50 copies per mL) on a stable ARV regimen for ≥3 months with no history of treatment failure and no known resistance to any component of BIKTARVY.

DHHS RECOMMENDED
AS AN INITIAL REGIMEN FOR
ADULTS WITH HIV-11

IMPORTANT SAFETY INFORMATION (cont'd)

BOXED WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B

  • Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of BIKTARVY. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue BIKTARVY. If appropriate, anti-hepatitis B therapy may be warranted.

Contraindications

  • Coadministration: Do not use BIKTARVY with dofetilide or rifampin.

Warnings and precautions

  • Drug interactions: See Contraindications and Drug Interactions sections. Consider the potential for drug interactions prior to and during BIKTARVY therapy and monitor for adverse reactions.
  • Immune reconstitution syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported.
  • New onset or worsening renal impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of tenofovir prodrugs. In clinical trials of BIKTARVY, there have been no cases of Fanconi syndrome or proximal renal tubulopathy (PRT). Do not initiate BIKTARVY in patients with estimated creatinine clearance (CrCl) <30 mL/min. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue BIKTARVY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.
    Renal monitoring: Prior to or when initiating BIKTARVY and during therapy, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients as clinically appropriate. In patients with chronic kidney disease, also assess serum phosphorus.
  • Lactic acidosis and severe hepatomegaly with steatosis: Fatal cases have been reported with the use of nucleoside analogs, including FTC and TDF. Discontinue BIKTARVY if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.

Adverse reactions

  • Most common adverse reactions (incidence ≥5%; all grades) in clinical studies were diarrhea (6%), nausea (5%), and headache (5%).

Drug interactions

  • Prescribing information: Consult the full prescribing information for BIKTARVY for more information on Contraindications, Warnings, and potentially significant drug interactions, including clinical comments.
  • Enzymes/transporters: Drugs that induce P-gp or induce both CYP3A and UGT1A1 can substantially decrease the concentration of components of BIKTARVY. Drugs that inhibit P-gp, BCRP, or inhibit both CYP3A and UGT1A1 may significantly increase the concentrations of components of BIKTARVY. BIKTARVY can increase the concentration of drugs that are substrates of OCT2 or MATE1.
  • Drugs affecting renal function: Coadministration of BIKTARVY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC and tenofovir and the risk of adverse reactions.

Dosage and administration

  • Dosage: 1 tablet taken once daily with or without food.
  • Renal impairment: Not recommended in patients with CrCl <30 mL/min.
  • Hepatic impairment: Not recommended in patients with severe hepatic impairment.
  • Prior to or when initiating: Test patients for HBV infection.
  • Prior to or when initiating, and during treatment: As clinically appropriate, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, assess serum phosphorus.

Pregnancy and lactation

  • Pregnancy: There is insufficient human data on the use of BIKTARVY during pregnancy. An Antiretroviral Pregnancy Registry (APR) has been established. Available data from the APR for FTC shows no difference in the rates of birth defects compared with a US reference population.
  • Lactation: Women infected with HIV-1 should be instructed not to breastfeed, due to the potential for HIV-1 transmission.

Please see full Prescribing Information for BIKTARVY® and DESCOVY®, including BOXED WARNINGS.

*ABC/3TC or FTC/TDF + boosted ATV or DRV regimen (cobicistat or ritonavir).

†E/C/F/TAF or E/C/F/TDF or ATV+RTV+FTC/TDF.

3TC, lamivudine; ABC, abacavir; AE, adverse event; ATV, atazanavir; C, cobicistat; DRV, darunavir; DTG, dolutegravir; eGFRCG, estimated glomerular filtration rate (Cockcroft-Gault); E, elvitegravir; F, emtricitabine; FTC, emtricitabine; M=F, missing equals failure; QD, once daily; RTV, ritonavir; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate.

References: 1. BIKTARVY [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2018. 2. Data on file. Gilead Sciences, Inc. 3. Gallant J, Lazzarin A, Mills A, et al. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Lancet. 2017;390(10107):2063-2072. 4. Sax PE, Pozniak A, Montes ML, et al. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet. 2017;390(10107):2073-2082. 5. Sax PE, Pozniak A, Montes ML, et al. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial [supplementary appendix]. Lancet. 2017;390(10107):2073-2082. 6. Kityo C, Hagins D, Koenig E, et al. Switching to bictegravir/emtricitabine/tenofovir alafenamide in women. Poster presented at: Conference on Retroviruses and Opportunistic Infections; March 4-7, 2018; Boston, MA. 7. Molina JM, Ward D, Brar I, et al. Switch to bictegravir/F/TAF from DTG and ABC/3TC. Oral presentation at: Conference on Retroviruses and Opportunistic Infections; March 4-7, 2018; Boston, MA. 8. Daar ES, DeJesus E, Ruane P, et al. Phase 3 randomized, controlled trial of switching to fixed-dose bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) from boosted protease inhibitor-based regimens in virologically suppressed adults: week 48 results. Oral presentation at: IDWeek; October 4-8, 2017; San Diego, CA.