BIKTARVY® | Clinical Studies in Treatment-Naïve Adults

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.

BIKTARVY^® is Backed by Robust Clinical Trial Experience^1-6

Extensive clinical trials with over 1400 adults including various age groups and ethnicities

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)

Virologically Suppressed Adult Women

STUDY 1961

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

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 Adults^1,2,7,8

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

Treatment-Naïve Adults
(N=629)

HIV-1 RNA ≥500 copies/mL
eGFR_CG ≥50 mL/min

1:1

n=314

n=315

BIKTARVY QD

ABC/DTG/3TC QD

Week 48
Primary endpoint

Week 96
Secondary endpoint

Primary endpoint

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

Secondary endpoint

Efficacy, safety, and tolerability were assessed at Week 96

Study 1489^2,7:
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 Adults^1,3,8,9

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

Treatment-Naïve Adults
(N=645)

HIV-1 RNA ≥500 copies/mL
eGFR_CG ≥30 mL/min

1:1

n=320

n=325

BIKTARVY QD

FTC/TAF+DTG QD

Week 48
Primary endpoint

Week 96
Secondary endpoint

Primary endpoint

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

Secondary endpoint

Efficacy, safety, and tolerability were assessed at Week 96

Study 1490^3,8,9:
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 Long-Term Efficacy in Treatment-Naïve Adults at Week 96^1-3,7-9

Results noninferior to comparators

Study 1489: Virologic Response

Virologic Response in Study 1489 and Study 1490

^‡95% confidence interval.

At Week 48, 1% of adults who received BIKTARVY experienced virologic failure vs 3% with ABC/DTG/3TC
At Week 96, 1% of adults who received BIKTARVY experienced virologic failure vs 2% with ABC/DTG/3TC

Study 1490: Virologic Response

^‡95% confidence interval.

At Week 48, 4% of adults who received BIKTARVY experienced virologic failure vs 1% with FTC/TAF+DTG
At Week 96, 4% of adults who received BIKTARVY experienced virologic failure vs 3% with FTC/TAF+DTG

In both studies, treatment outcomes were similar across subgroups, regardless of age, sex, race, baseline viral load, and baseline CD4+ cell count⁸

No Treatment-Emergent Resistance Associated With BIKTARVY^1-3,7-9

In two large phase 3 clinical trials in treatment-naïve adults through Week 96

cases of resistance with
BIKTARVY

Among 634 treatment-naïve adults in Studies 1489 and 1490, 7 treatment-failure subjects were tested and no amino acid substitutions emerged that were associated with BIKTARVY resistance

Week 48:
Study 1489 Virologic Outcomes^1,7,8*

Week 48

BIKTARVY^®(n=314)

ABC/
DTG/
3TC(n=315)

Week 96

BIKTARVY(n=314)

ABC/
DTG/3TC(n=315)

HIV-1 RNA <50 copies/mL	92%	93%	88%	90%
Treatment difference (95% CI) BIKTARVY vs comparator	-0.6%(-4.8% to 3.6%)		-1.9%(-6.9% to 3.1%)
HIV-1 RNA ≥50 copies/mL^†	1%	3%	1%	2%
No virologic data	7%	4%	11%	8%
Discontinued study drug due to AE or death^‡	0%	1%	<1%	2%
Discontinued study drug due to other reasons and last available HIV-1 RNA <50 copies/mL^§	5%	3%	10%	5%
Missing data during window but on study drug	2%	<1%	1%	1%

Week 96:
Study 1489 Virologic Outcomes^1,7,9*

BIKTARVY(n=314)

ABC/DTG/
3TC(n=315)

HIV-1 RNA <50 copies/mL	88%	90%
Treatment difference (95% CI) BIKTARVY vs comparator	-1.9%(6.9% to 3.1%)
HIV-1 RNA ≥50 copies/mL^†	1%	2%
No virologic data	11%	8%
Discontinued study drug due to AE or death^‡	<1%	2%
Discontinued study drug due to other reasons and last available HIV-1 RNA <50 copies/mL^§	10%	5%
Missing data during window but on study drug	1%	1%

*Week 48 window was between Day 295 and 378 (inclusive); Week 96 window was between Day 631 and 754 (inclusive).

^†Includes subjects who had ≥50 copies/mL in the Week 48 or 96 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 through week 96 were diarrhea (6%), nausea (6%), and headache (5%).

CI, confidence interval.

Week 48:
Study 1490 Virologic Outcomes^1,8,9*

Week 48

BIKTARVY^®(n=320)

FTC/TAF
+DTG(n=325)

Week 96

BIKTARVY(n=320)

FTC/TAF
+DTG(n=325)

HIV-1 RNA <50 copies/mL	89%	93%	84%	86%
Treatment difference (95% CI) BIKTARVY vs comparator	-3.5%(-7.9% to 1.0%)		-2.3%(-7.9% to 3.2%)
HIV-1 RNA ≥50 copies/mL^†	4%	1%	4%	3%
No virologic data	6%	6%	12%	11%
Discontinued study drug due to AE or death^‡	1%	1%	3%	2%
Discontinued study drug due to other reasons and last available HIV-1 RNA <50 copies/mL^§	3%	4%	8%	7%
Missing data during window but on study drug	2%	1%	1%	1%

Week 96:
Study 1490 Virologic Outcomes^1,8,9*

BIKTARVY(n=320)

FTC/TAF
+DTG(n=325)

HIV-1 RNA <50 copies/mL	84%	86%
Treatment difference (95% CI) BIKTARVY vs comparator	-2.3%(-7.9% to 3.2%)
HIV-1 RNA ≥50 copies/mL^†	4%	3%
No virologic data	12%	11%
Discontinued study drug due to AE or death^‡	3%	2%
Discontinued study drug due to other reasons and last available HIV-1 RNA <50 copies/mL^§	8%	7%
Missing data during window but on study drug	1%	1%

*Week 48 window was between Day 295 and 378 (inclusive); Week 96 window was between Day 631 and 714 (inclusive).

^‡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 through week 96 were diarrhea (6%), nausea (6%), and headache (5%).

CI, confidence interval.

INDICATION

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 through week 96 were diarrhea (6%), nausea (6%), 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; eGFR_CG, 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. 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. 3. Sax PE, Pozniak A, Montes ML, et al. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for the initial treatment of HIV-1 infection (GS-US-1490): a randomised, double-blind, multicenter, phase 3, non-inferiority trial. Lancet. 2017;390(10107):2073-2082. 4. Molina JM, Ward, D, Brar I, et al. Switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from dolutegravir plus abacavir and lamivudine in virologically suppressed adults with HIV-1: 48 week results of a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. Lancet HIV. 2018;5(7):e357-e365. 5. Daar ES, DeJesus E, Ruane P, et al. Efficacy and safety of switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically suppressed adults with HIV-1: 48 week results of a randomised, open-label, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2018;5(7):e347-e356. 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. Wohl D, Yazdanpanah Y, Baumgarten A, et al. A phase 3, randomized, controlled clinical trial of bictegravir in a fixed-dose combination, B/F/TAF, vs DTG/ABC/3TC in treatment-naïve adults at week 96. Oral presentation at: IDWeek; October 3-7, 2018; San Francisco, CA. 8. Data on file. Gilead Sciences, Inc. 9. Stellbrink HJ, Arribas J, Stephens JL, et al. Phase III randomized, controlled clinical trial of bictegravir coformulated with FTC/TAF in a fixed-dose combination (B/F/TAF) versus dolutegravir (DTG) + F/TAF in treatment-naïve HIV-1 positive adults: week 96. Oral presentation at: HIV Drug Therapy; October 28-31, 2018; Glasgow, UK.