Drugs

Drug Trials Snapshot: BIKTARVY

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

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Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to the BIKTARVY Package Insert for complete information.

BIKTARVY (bictegravir/emtricitabine/tenofovir alafenamide)
(bik-TAR-vee)
Gilead Sciences
Approval date: February 7, 2018


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

BIKTARVY is a drug for the treatment of human immunodeficiency virus 1 (HIV-1) infection in adults. BIKTARVY is a combination of three antiviral drugs in a single tablet: bictegravir (new drug for HIV-1 treatment), emtricitabine, and tenofovir alafenamide (previously approved for HIV-1 treatment).

HIV-1 is the virus that causes AIDS (Acquired Immune Deficiency Syndrome).

How is this drug used?

BIKTARVY is a tablet that is taken once daily with or without food.

What are the benefits of this drug?

In patients with HIV-1 infection, BIKTARVY decreases viral load (number of HIV-1 copies in the blood) and increases the number of immune cells in the blood (CD4 count).

What are the benefits of this drug (results of trials used to assess efficacy)?

The table below summarizes the primary efficacy endpoint at Week 48 for the two clinical trials in treatment-naïve patients.

Table 2. Virologic Outcomes of Randomized Treatment in Trials 1489 and 1490 at Week 48a in Patients with No Antiretroviral Treatment History

 Trial 1489Trial 1490
 BIKTARVY
(N=314)
ABC/DTG/3TC*
(N=315)
BIKTARVY
(N=320)
FTC/TAF+DTG**
(N=325)
HIV-1 RNA < 50 copies/mL92%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/mLb1%3%4%1%
No Virologic Data at Week 48 Window7%4%6%6%
Discontinued Study Drug Due to Adverse Event or Deathc01%1%1%
Discontinued Study Drug Due to Other Reasons and Last Available HIV-1 RNA <50 copies/mLd5%3%3%4%
Missing Data During Window but on Study Drug2%<1%2%1%

*ABC: abacavir; DTG: dolutegravir; 3TC: lamivudine
**FTC: emtricitabine; TAF: tenofovir alafenamide

a. Week 48 window was between Day 295 and 378 (inclusive).
b. Includes patients who had ≥ 50 copies/mL in the Week 48 window; patients who discontinued early due to lack or loss of efficacy; patients 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.
c. Includes patients who discontinued due to Adverse Event 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.
d. Includes patients who discontinued for reasons other than an Adverse Event, death, or lack or loss of efficacy, e.g., withdrew consent, loss to follow-up, etc.

BIKTARVY Prescribing Information

The table below summarizes the primary efficacy endpoint at Week 48 for the two clinical trials in virologically-suppressed patients.

Table 3. Virologic Outcomes of Trials 1844 and 1878 at Week 48a in Virologically-Suppressed Patients Who Switched to BIKTARVY

 Trial 1844Trial 1878
 BIKTARVY
(N=282)
ABC/DTG/3TC*
(N=281)
BIKTARVY
(N=290)
ATV- or DRV-based regimen**
(N=287)
HIV-1 RNA ≥ 50 copies/mLb1%<1%2%2%
Treatment Difference (95% CI) BIKTARVY vs. Comparator0.7% (-1.0% to 2.8%)0.0% (-2.5% to 2.5%)
HIV-1 RNA < 50 copies/mL94%95%92%89%
No Virologic Data at Week 48 Window5%5%6%9%
Discontinued Study Drug Due to Adverse Event or Death and Last Available HIV-1 RNA < 50 copies/mL2%1%1%1%
Discontinued Study Drug Due to Other Reasons and Last Available HIV-1 RNA < 50 copies/mLc2%3%3%7%
Missing Data During Window but on Study Drug2%1%2%2%

*ABC: abacavir; DTG: dolutegravir; 3TC: lamivudine
**ATV: atazanavir; DRV: darunavir

a. Week 48 window was between Day 295 and 378 (inclusive).
b. Includes patients who had ≥ 50 copies/mL in the Week 48 window; patients who discontinued early due to lack or loss of efficacy; patients who discontinued for reasons other than lack or loss of efficacy and at the time of discontinuation had a viral value of ≥ 50 copies/mL.
c. Includes patients who discontinued for reasons other than an Adverse Event, death, or lack or loss of efficacy, e.g., withdrew consent, loss to follow-up, etc.

BIKTARVY Prescribing Information

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

  • Sex: BIKTARVY worked similarly in men and women.
  • Race: BIKTARVY worked similarly in White and Black or African American patients. The number of patients in other races was small; therefore, differences in how the drug worked in other races could not be determined.
  • Age: BIKTARVY worked similarly in patients below or above 50 years of age. The number of patients older than 65 years of age was small. Therefore, differences in how well the drug worked in patients above 65 years of age could not be determined.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

The tables below summarize the responses to BICTARVY by sex, race and age subgroups for patients with no antiretroviral treatment history and virologically-suppressed patients who switched to BICTRAVY.

Table 4. Proportion of Patients with HIV-1 RNA <50 copies at Week 48 By Sex, Race and Age in Patients with No Antiretroviral Treatment History - Trials 1489 and 1490

 Trial 1489aTrial 1490b
 BIKTARVY
n/N (%)
ABC/DTG/3TC*
n/N (%)
% Difference
(95% CI)
BIKTARVY
n/N (%)
FTC/TAF+DTG**
n/N (%)
% Difference
(95% CI)
Overall290/314
(92)
293/315
(93)
-0.6
(-4.8, 3.6)
286/320
(89)
302/325
(93)
-3.5
(-7.9, 1.0)
Sex
Men263/285
(92)
263/282
(93)
-0.9
(-5.4, 3.5)
252/280
(91)
270/288
(94)
-3.6
(-8.2, 1.0)
Women27/29
(93)
30/33
(91)
2.2
(-11.3,15.7)
34/40
(85)
32/37
(86)
-1.2
(-18.5, 16)
Race
Non-Black184/198
(92)
188/203
(93)
0.1
(-5.2, 5.5)
203/223
(91)
210/225
(93)
-2.1
(-7.2, 3.0)
Black104/114
(91)
105/112
(94)
-2.5
(-9.4, 4.3)
83/97
(86)
92/100
(92)
-6.4
(-15.2, 2.4)
Age
< 65 years288/312
(92)
291/313
(93)
-0.6
(-4.8, 3.6)
284/317
(90)
300/323
(93)
-3.3
(-7.7, 1.2)
≥65 years2/2
(100)
2/2
(100)
NA2/3
(67)
2/2
(100)
-33.3
(-86.7, 20)
<50 years250/274
(91)
256/274
(93)
-2.1
(-6.7, 2.5)
237/264
(90)
246/266
(92)
-2.7
(-7.7, 1.2)
≥50 years40/40
(100)
37/41
(90)
8.9
(-3.7, 21.4)
49/56
(88)
56/59
(95)
-7.4
(-19.3, 4.4)

a.89% of non-Black patients were White
b.84% of non-Black patients were White

* ABC: abacavir; DTG: dolutegravir; 3TC: lamivudine
** FTC: emtricitabine; TAF: tenofovir alafenamide

Clinical trial data

Table 5. Treatment Differences in HIV-1 RNA ≥ 50 copies/mL at Week 48 in Virologically-Suppressed Patients Who Switched to BIKTARVY – Trials 1844 and 1878

 Trial 1844aTrial 1878b
 BIKTARVY
n/N (%)
ABC/DTG/3TC*
n/N (%)
% Difference
(95% CI)
BIKTARVY
n/N (%)
ATV- or DRV-based regimen**
n/N (%)
% Difference
(95% CI)
Overall3/282
(1.1)
1/281
(0.4)
0.7
(-1, 2.8)
5 /290
(1.7)
5/287
(1.7)
-0.0
(-2.5, 2.5)
Sex
Men3/247
(1.2)
1/252
(0.4)
-0.8
(-1.2, 3.2)
5/243
(2.1)
5/234
(2.1)
-0.1
(-3.1, 2.9)
Women0/35
(0)
0/29
(0)
NA0/47
(0)
0/53
(0)
NA
Race
Non-Black3/223
(1.3)
0/216
(0)
1.3
(-0.4, 3.9)
4/211
(1.9)
3/215
(1.4)
0.5
(-2.4, 3.6)
Black0/59
(0)
1/62
(1.6)
-1.6
(-8.8, 4.7)
1/79
(1.3)
2/72
(2.8)
-1.5
(-8.6, 4.7)
Age
< 65 years3/268
(1)
1/271
(0.4)
0.8
(-1.1, 2.9)
5/279
(1.8)
5/276
(1.8)
-0.0
(-2.6, 2.6)
≥65 years0/14
(0)
0/10
(0)
NA0/11
(0)
0/11
(0)
NA
<50 years1/158
(0.6)
0/177
(0)
0.6
(-1.5, 3.6)
3/164
(1.8)
5/175
(2.9)
-1.0
(-5.0, 2.9)
≥50 years2/124
(1.6)
1/104
(1.0)
0.7
(-3.8, 4.9)
2/126
(1.6)
0/112
(0)
1.6
(-1.8, 5.7)

a. 90% of non-Black patients were White
b. 89% of non-Black patients were White

* ABC: abacavir; DTG: dolutegravir; 3TC: lamivudine
** ATV: atazanavir; DRV: darunavir

Clinical trial data

What are the possible side effects?

BIKTRAVY may cause serious side effects:

  • Worsening of hepatitis B infection may occur after discontinuation of BIKTARVY treatment in patients infected with HIV-1 and hepatitis B.
  • During the initial phase of treatment with BIKTARVY, the immune system may get stronger and begin to fight infections that were hidden (a condition called immune reconstitution syndrome).
  • New or worsening kidney problems.
  • Build-up of lactic acid in the blood with enlargement of the liver, which may be fatal.

The most common side effects of BIKTARVY include diarrhea, nausea, and headache.

What are the possible side effects (results of trials used to assess safety)?

The table below summarizes adverse reactions from the trials in for patients with no antiretroviral treatment history.

Table 6. Adverse Reactionsa Reported in ≥ 2% of HIV-1 Infected Adults with No Antiretroviral Treatment History Receiving BIKTARVY in Trials 1489 or 1490 (Week 48 Analysis)

 Trial 1489Trial 1490
Adverse ReactionsBIKTARVY
N=314
ABC/DTG/3TC*
N=315
BIKTARVY
N=320
FTC/TAF+DTG**
N=325
Diarrhea6%4%3%3%
Nausea5%17%3%5%
Headache5%5%4%3%
Fatigue3%3%2%2%
Abnormal dreams3%3%<1%1%
Dizziness2%3%2%1%
Insomnia2%3%2%<1%

a. Frequencies of adverse reactions are based on all adverse events attributed to trial drugs by the investigator. No adverse reactions of Grade 2 or higher occurred in ≥ 1% of subjects treated with BIKTARVY.

*ABC: abacavir; DTG: dolutegravir; 3TC: lamivudine
**FTC: emtricitabine; TAF: tenofovir alafenamide

BIKTARVY Prescribing Information

Adverse reactions from the trials in virologically-suppressed patients

The safety of BIKTARVY at Week 48 in 282 virologically-suppressed adults who were switched to BIKTARVY from dolutegravir plus abacavir plus lamivudine (Trial 1844) and in 280 virologically-suppressed adults who were switched to BIKTARVY from a regimen containing atazanavir or darunavir plus either emtricitabine/tenofovir or abacavir/lamivudine (Trial 1878) was similar to that in patients with no antiretroviral treatment history.

BIKTARVY Prescribing Information

Were there any differences in side effects among sex, race and age?

  • Sex: The occurrence of side effects was similar in men and women.
  • Race: The occurrence of side effects was similar in White and Black or African American patients. The number of patients in other races was small; therefore, differences in side effects among other races could not be determined.
  • Age: The occurrence of side effects was similar in patients younger or older than 50 years of age. The number of patients 65 years of age or older was small; therefore, differences in side effects among patients older than 65 years of age could not be determined.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

Table 7. Frequency of Treatment-Emergent Adverse Events (TEAE) by Sex, Race and Age in Treatment -Naïve Patients–Trials 1489 and 1490

 BIKTARVY
n/N (%)
ABC/DTG/3TC*
n/N (%)
DTG/F/TAF**
n/N (%)
N of Patients with at least one TEAE530/634 (84)283/315 (89)272/325 (84)
Sex
Men472/565 (84)253/282 (89)244/288 (85)
Women58/69 (84)30/33 (91)28/37 (76)
Race
White300/363 (83)163/179 (91)161/195 (83)
Black or African American175/211 (83)98/112 (87)82/100 (82)
Asian10/13 (77)9/10 (90)9/10 (90)
All Other45/47 (95)13/14 (93)20/20 (100)
Age
Less than 50 years448/538 (83)246/274 (90)225/266 (84)
50 years or older82/96 (85)37/41 (90)47/59 (80)
Less than 65 years525/629 (83)281/313 (90)271/323 (84)
65 years or older5/5 (100)2/2 (100)1/2 (50)

*ABC: abacavir; DTG: dolutegravir; 3TC: lamivudine
**FTC: emtricitabine; TAF: tenofovir alafenamide

Clinical trial data

Table 8. Frequency of Treatment-Emergent Adverse Events by Sex, Race and Age in Virologically-Suppressed Patients Who Were Switched to BIKTARVY – Trials 1844 and 1878

 Trial 1844Trial 1878
 BIKTARVY
n/N (%)
ABC/DTG/3TC*
n/N (%)
BIKTRAVY
n/N (%)
ATV or DRV Based Regimen**
n/N (%)
Patients with at least one TEAE225/282 (80)225/281 (80)238/290 (82)232/287 (81)
Sex
Men198/247 (80)201/252 (80)197/243 (81)192/234 (82)
Women27/35 (77)24/29 (83)41/47 (87)40/53 (75)
Race
White168/206 (82)168/202 (83)155/188 (82)157/190 (83)
Black or African American45/59 (82)42/62(68)60/79 (76)57/72 (72)
Asian5/9 (55)8/9 (89)6/6 (100)7/10 (70)
All Other7/8 (88)7/8 (88)14/17 (82)11/15 (73)
Age
Less than 50 years126/158 (80)138/177 (78)140/164 (85)139/175 (79)
50 years or older99/124 (80)87/104 (84)98/126 (78)93/112 (83)
Less than 65 years214/268 (80)216/269 (80)230/279 (82)222/276 (80)
65 years or older11/14 (80)9/12 (75)8/11 (73)10/11 (91)

*ABC: abacavir; DTG: dolutegravir; 3TC: lamivudine
**ATV: atazanavir; DRV: darunavir

Clinical trial data

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved BIKTARVY based on evidence from four clinical trials of 2,414 adult patients with HIV-1 infection. Two trials (Trial 1489-NCT 02607930, and Trial 1490- NCT 02607956) studied patients who had not received antiretroviral therapy in the past, and two trials (Trial 1844-NCT 0260312, and Trial 1878-NCT 02603107) studied patients who were treated with antiretroviral drugs that had resulted in suppression of HIV viral load for at least 3 months and who were switched to BIKTARVY.

The trials were conducted at 465 centers in 34 countries including the United States.

Figures 1, 2, and 3 summarize how many patients participated in the clinical trials by sex, race and age.

Figure 1. Baseline Demographics by Sex

Pie chart summarizing how many men and women were in the clinical trials. In total, 2111 men (87%) and  303 women (13%) participated in the clinical trials

FDA review

Figure 2. Baseline Demographics by Race

 Pie chart summarizing the percentage of patients by race in clinical trials. In total, 1523 Whites (63%), 695 Blacvk or African Americans (29%), 67 Asians (3%), and 129 Other (5%), participated in the clinical trials.

FDA review

Table 1. Baseline Demographics by Race

 Number of PatientsPercentage
Race
White152363
Black or African American69529
Asian673
American Indian or Alaska Native18less than 1
Native Hawaiian or Pacific Islander7less than 1
Other/Unknown1044

FDA review

Figure 3. Baseline Demographics by Age

Pie charts summarizing how many individuals of certain age groups were in the clinical trial.s In total, 1752 patients  were younger than 50 years (73%), 607 were 50 to 65 years old (25%) and  55 patients were  65 years and older (2%)

FDA review

Who participated in the trials?

The demographics from four clinical trials of 2,414 adults with HIV-1 infection are presented below. The Full Set Analysis (FAS) population was defined as all randomized patients who received at least one dose of study drug.

Table 9. Demographics – FAS Population

 Trial 1489
N=629
n(%)
Trial 1490
N = 645
n(%)
Trial 1844
N = 563
n(%)
Trial 1878
N = 577
n(%)
Total
N = 2414
Sex
Men567 (90)568 (88)499 (89)477 (83)2111 (87)
Women62 (10)77 (12)64 (11)100 (17)303 (13)
Race
White359 (57)378 (59)408 (73)378 (66)1573 (63)
Black or African American226 (36)197 (30)121 (21)151 (26)695 (29)
Asian16 (3)17 (3)18 (3)16 (3)67 (3)
American Indian or Alaska Native6 (1)2 (< 1)4 (< 1)6 (1)13 (< 1)
Native Hawaiian or Pacific Islander3 (< 1)1 (< 1)3 (< 1)07 (< 1)
Other/Unknown19 (3)50 (7)9 (1.6)26 (4)104 (4)
Age
Less than 65 years625 (99)640 (99)539 (96)555 (96)2359 (98)
65 years or older4 (< 1)5 (< 1)24 (4)22 (4)55 (2)
Less than 50 years548 (87)530 (72)335 (59)339 (59)1752 (73)
50 years or older81 (13)115 (18)228 (41)238 (41)662 (27)
Ethnicity
Hispanic or Latino137 (22)164 (25)98 (18)107 (19)506 (21)
Not Hispanic or Latino489 (78)481 (75)463 (82)470 (82)1903 (79)
Not Reported3 (< 1)02 (< 1)05 (< 1)
Geographic Region
United States461 (73)386 (60)399 (71)330 (57)1576 (65)
Rest of the World168 (27)259 (40)164 (29)247 (43)838 (35)

Adapted from FDA review

How were the trials designed?

The benefits and side effects of BIKTARVY were studied in four clinical trials. Two trials were in adults who had not received HIV-1 treatment in the past. In these two trials, patients were randomly assigned to receive either BIKTARVY or another HIV-1 treatment, and neither the patient or the healthcare provider knew which treatment was being given until after the trials were completed.

The other two trials were in patients who were receiving HIV-1 treatment that had resulted in suppression of HIV-1 viral load. These patients were randomly assigned to continue their treatment or switch to BIKTARVY. In one trial (Trial 1844), neither the patients or the healthcare providers knew which medication was being given until after the trial was completed. In the other trial (Trial 1878), both, patients and healthcare providers knew which medication was being given.

The benefit of BICTRAVY in all four trials was assessed by measuring the number of HIV-1 copies in the blood after 48 weeks of treatment.

How were the trials designed?

The benefits and side effects of BIKTARVY were studied in four clinical trials.

Trials 1489 and 1490 were randomized, double-blind, active-controlled trials and were conducted in HIV-1 infected adults with no antiretroviral treatment history. Trials 1844 and 1878 were conducted in adults who were virologically-suppressed on another regimen and who were switched to BIKTRAVY; Trial 1844 was randomized, double-blind, active controlled, and trial 1878 was randomized, open-label, active controlled.

The primary outcome for Trials 1489 and 1490 was the the proportion of subjects with HIV RNA <50 copies at Week 48 and the primary outcome for Trials 1878 and 1844 was the proportion of subjects with HIV RNA ≥ 50 copies/ml at Week 48.

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

PRESCRIBING INFORMATION

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