DESCOVY (Page 7 of 9)

13.2 Animal Toxicology and/or Pharmacology

Minimal to slight infiltration of mononuclear cells in the posterior uvea was observed in dogs with similar severity after three- and nine-month administration of TAF; reversibility was seen after a three-month recovery period. No eye toxicity was observed in the dog at systemic exposures of 5 (TAF) and 15 (tenofovir) times the exposure seen in humans with the recommended daily TAF dose in DESCOVY.

14 CLINICAL STUDIES

14.1 Overview of Clinical Trials

The efficacy and safety of DESCOVY have been evaluated in the trials summarized in Table 15.

Table 15 Trials Conducted with FTC+TAF-Containing Products for HIV-1 Treatment and DESCOVY for HIV-1 PrEP
Trial Population Study Arms (N) Timepoint
*
Randomized, double-blind, active-controlled study.
Administered as GENVOYA®.
Administered as STRIBILD®.
§
Randomized, open-label, active controlled trial.
HIV-1 RNA less than 50 copies per mL.
#
Open label trial
Þ
Estimated creatinine clearance between 30 and 69 mL per minute by Cockcroft-Gault method.
ß
End stage renal disease (estimated creatinine clearance of less than 15 mL per minute by Cockcroft-Gault method).
à
Administered as BIKTARVY®.
è
Exposure in the DESCOVY group.
Study 104 *(NCT01780506)Study 111 *(NCT01797445) HIV-1 infected treatment-naïve adults FTC+TAF with EVG+COBI (866)FTC+TDF with EVG+COBI (867) 48 Weeks
Study 109 §(NCT01815736) HIV-1 infected virologically suppressed adults FTC+TAF with EVG+COBI (799)ATRIPLA® or TRUVADA® +atazanavir+cobicistat or ritonavir or FTC+TDF with EVG+COBI (397) 48 Weeks
Study 112 #(NCT01818596) HIV-1 infected virologically-suppressed adults with renal impairment Þ FTC+TAF with EVG+COBI (242) 24 Weeks
Study 1825 #(NCT02600819) HIV-1 infected virologically-suppressed adults with ESRD ß receiving chronic hemodialysis FTC+TAF with EVG+COBI (55) 48 Weeks
Study 106 #(Cohort 1)(NCT01854775) HIV-1 infected treatment-naïve adolescents between the ages of 12 to less than 18 years (at least 35 kg) FTC+TAF with EVG+COBI (50) 48 Weeks
Study 106 #(Cohort 2)(NCT01854775) HIV-1 infected, virologically suppressed children between the ages of 6 to less than 12 years (at least 25 kg) FTC+TAF with EVG+COBI (52) 48 Weeks
Study 1474 # (Cohort 3) (NCT02881320) HIV-1 infected, virologically suppressed children at least 2 years (at least 14 kg and less than 25 kg) FTC+TAF with bictegravir à (22) 24 Weeks
DISCOVER *(NCT02842086) HIV-1 uninfected men or transgender women who have sex with men DESCOVY (2,670)TRUVADA® (2,665) 4,370 person-years è

14.2 Clinical Trial Results for Treatment of HIV-1

Clinical Trials in Adults with HIV-1

In trials of FTC+TAF with EVG+COBI in HIV-1 infected adults as initial therapy in those with no antiretroviral treatment history (N=866) and to replace a stable antiretroviral regimen in those who were virologically-suppressed for at least 6 months with no known resistance substitutions (N=799), 92% and 96% of patients in the two populations, respectively, had HIV-1 RNA less than 50 copies per mL at Week 48.

Clinical Trials in Pediatric Patients with HIV-1

An open-label, single arm trial of FTC+TAF with EVG+COBI enrolled 50 treatment-naïve HIV-1 infected adolescents aged 12 to less than 18 years weighing at least 35 kg (cohort 1) and 52 virologically suppressed children aged 6 to less than 12 years weighing at least 25 kg (cohort 2). In cohort 1, the virologic response rate (i.e., HIV-1 RNA less than 50 copies per mL) was 92% (46/50) and the mean increase from baseline in CD4+ cell count was 224 cells per mm3 at Week 48. In cohort 2, 98% (51/52) of subjects remained virologically suppressed at Week 48. From a mean (SD) baseline CD4+ cell count of 961 (275.5) cells per mm3 , the mean change from baseline in CD4+ cell count was -66 cells per mm3 and the mean (SD) change in CD4% was -0.6% (4.4%) at Week 48. All subjects maintained CD4+ cell counts above 400 cells/mm3 [see Adverse Reactions (6.1) and Use in Specific Populations (8.4)].

In a separate open-label single arm trial of FTC+TAF with bictegravir that enrolled 24 virologically-suppressed children at least 2 years of age and weighing at least 14 to less than 25 kg (cohort 3), 91% (20/22) of subjects remained virologically suppressed at Week 24. From a mean (SD) baseline CD4+ count of 1104 (440), the mean (SD) change from baseline in CD4+ cell count was −126 (264) cells per mm3 , and the mean (SD) change in CD4% was 0.2% (4.4%) at Week 24.

Clinical Trials in Adults with HIV-1 and Renal Insufficiency

In a trial in 248 HIV-1 infected adults with estimated creatinine clearance greater than 30 mL per minute but less than 70 mL per minute, 95% (235/248) of the combined population of treatment-naïve subjects began on FTC+TAF with EVG+COBI (N=6) and those previously virologically-suppressed on other regimens and switched to FTC+TAF with EVG+COBI (N=242) had HIV-1 RNA less than 50 copies per mL at Week 24.

In a trial in 55 HIV-1 infected virologically-suppressed adults with ESRD (estimated creatinine clearance of less than 15 mL per minute) receiving chronic hemodialysis for at least 6 months who switched to FTC+TAF with EVG+COBI, 82% (45/55) maintained HIV-1 RNA less than 50 copies per mL at Week 48. Two subjects had HIV-1 RNA ≥ 50 copies per mL by Week 48, 7 discontinued due to AE or other reasons while suppressed, and 1 did not have an HIV-1 RNA measurement at Week 48.

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