生产厂家】:Epizyme, Inc

【商品名】:Tazverik 

【药品名】:tazemetostat

 

【Tazverik作用机理】

1.Tazemetostat是甲基转移酶EZH2和一些EZH2功能获得性突变的抑制剂，包括Y646X，A682G和A692V。Tazemetostat还以392 nM的一半最大抑制浓度（IC50）抑制EZH1，约为抑制EZH2的IC50的36倍。

2.EZH2最有特色的功能是作为多梳抑制复合物2（PRC2）的催化亚基，催化组蛋白H3的赖氨酸27的单，二和三甲基化。组蛋白H3的三甲基化导致转录抑制。

3.SWItch/蔗糖不可发酵（SWI/SNF）复合物可拮抗PRC2在上皮样肉瘤患者某些基因表达的调节中的功能。某些SWI/SNF复杂成员（例如整合酶相互作用子1[INI1/SNF5/SMARCB1/BAF47]，SMARCA4和SMARCA2）丧失或功能异常的临床前体外和体内模型可导致异常的EZH2活性或表达并导致致癌对EZH2的依赖。

4.Tazemetostat在体外抑制B细胞淋巴瘤细胞系的增殖，并在具有或不具有EZH2功能获得性突变的B细胞淋巴瘤的小鼠异种移植模型中显示出抗肿瘤活性。

5.Tazemetostat证明对具有突变EZH2的淋巴瘤细胞系增殖的抑制作用更大。

 

【Tazverik适应症和用途】

TAZVERIK是一种甲基转移酶抑制剂，可用于治疗：

1.16岁及以上患有转移性或局部晚期上皮样肉瘤的成人和儿科患者不符合完全切除的条件

2.成人复发或难治性滤泡性淋巴瘤患者，其肿瘤经美国食品药品管理局（FDA）批准的检测为EZH2突变阳性，并且至少接受过2种先前的全身疗法。

3.成人复发或难治性滤泡性淋巴瘤患者，没有令人满意的替代治疗选择。

这些指示根据总体响应率和响应时间在加速批准下获得批准。这些适应症的持续批准可能取决于验证试验中对临床益处的验证和描述。

 

【Tazverik剂量和给药】

建议的剂量为800毫克，每天口服两次，带或不带食物。

剂量形式和强度

片：200毫克

 

 

【Tazverik警告和注意事项】

1.继发性恶性肿瘤：TAZVERIK增加了发生继发性恶性肿瘤的风险，包括T细胞淋巴母细胞淋巴瘤，骨髓增生异常综合症和急性髓细胞性白血病。长期监测患者的继发性恶性肿瘤的发展。

2.胚胎-胎儿毒性：可引起胎儿伤害。建议患者有胎儿潜在危险，并使用有效的非激素避孕方法。

 

【Tazverik不良反应】

1.上皮样肉瘤患者最常见的不良反应（≥20％）为疼痛，疲劳，恶心，食欲下降，呕吐和便秘。

2.滤泡性淋巴瘤患者最常见的不良反应（≥20％）是疲劳，上呼吸道感染，肌肉骨骼痛，恶心和腹痛。

 

 

【Tazverik药物相互作用】

1.强和中度细胞色素P450（CYP）3A抑制剂：避免将强和中度CYP3A抑制剂与TAZVERIK并用。

如果无法避免与中度CYP3A抑制剂并用，减低TAZVERIK的剂量。

2.强和中度CYP3A诱导剂：避免与TAZVERIK共同给药。

 

【Tazverik在特定人群中的使用】

哺乳期：建议不要母乳喂养。

 

【Tazverik包装供应/存储和处理方式】

TAZVERIK 200mg薄膜衣片为红色，圆形，双凸形，一侧凹陷有“ EZM 200”，另一侧凹陷了。 TAZVERIK可用于：

装有干燥剂的240片瓶； NDC 72607-100-00

请勿在30°C（86°F）以上的温度下存放。

生产厂家】:Epizyme, Inc

【商品名】:Tazverik 

【药品名】:tazemetostat

 

【Tazverik作用机理】

1.Tazemetostat是甲基转移酶EZH2和一些EZH2功能获得性突变的抑制剂，包括Y646X，A682G和A692V。Tazemetostat还以392 nM的一半最大抑制浓度（IC50）抑制EZH1，约为抑制EZH2的IC50的36倍。

2.EZH2最有特色的功能是作为多梳抑制复合物2（PRC2）的催化亚基，催化组蛋白H3的赖氨酸27的单，二和三甲基化。组蛋白H3的三甲基化导致转录抑制。

3.SWItch/蔗糖不可发酵（SWI/SNF）复合物可拮抗PRC2在上皮样肉瘤患者某些基因表达的调节中的功能。某些SWI/SNF复杂成员（例如整合酶相互作用子1[INI1/SNF5/SMARCB1/BAF47]，SMARCA4和SMARCA2）丧失或功能异常的临床前体外和体内模型可导致异常的EZH2活性或表达并导致致癌对EZH2的依赖。

4.Tazemetostat在体外抑制B细胞淋巴瘤细胞系的增殖，并在具有或不具有EZH2功能获得性突变的B细胞淋巴瘤的小鼠异种移植模型中显示出抗肿瘤活性。

5.Tazemetostat证明对具有突变EZH2的淋巴瘤细胞系增殖的抑制作用更大。

 

【Tazverik适应症和用途】

TAZVERIK是一种甲基转移酶抑制剂，可用于治疗：

1.16岁及以上患有转移性或局部晚期上皮样肉瘤的成人和儿科患者不符合完全切除的条件

2.成人复发或难治性滤泡性淋巴瘤患者，其肿瘤经美国食品药品管理局（FDA）批准的检测为EZH2突变阳性，并且至少接受过2种先前的全身疗法。

3.成人复发或难治性滤泡性淋巴瘤患者，没有令人满意的替代治疗选择。

这些指示根据总体响应率和响应时间在加速批准下获得批准。这些适应症的持续批准可能取决于验证试验中对临床益处的验证和描述。

 

【Tazverik剂量和给药】

建议的剂量为800毫克，每天口服两次，带或不带食物。

剂量形式和强度

片：200毫克

 

 

【Tazverik警告和注意事项】

1.继发性恶性肿瘤：TAZVERIK增加了发生继发性恶性肿瘤的风险，包括T细胞淋巴母细胞淋巴瘤，骨髓增生异常综合症和急性髓细胞性白血病。长期监测患者的继发性恶性肿瘤的发展。

2.胚胎-胎儿毒性：可引起胎儿伤害。建议患者有胎儿潜在危险，并使用有效的非激素避孕方法。

 

【Tazverik不良反应】

1.上皮样肉瘤患者最常见的不良反应（≥20％）为疼痛，疲劳，恶心，食欲下降，呕吐和便秘。

2.滤泡性淋巴瘤患者最常见的不良反应（≥20％）是疲劳，上呼吸道感染，肌肉骨骼痛，恶心和腹痛。

 

 

【Tazverik药物相互作用】

1.强和中度细胞色素P450（CYP）3A抑制剂：避免将强和中度CYP3A抑制剂与TAZVERIK并用。

如果无法避免与中度CYP3A抑制剂并用，减低TAZVERIK的剂量。

2.强和中度CYP3A诱导剂：避免与TAZVERIK共同给药。

 

【Tazverik在特定人群中的使用】

哺乳期：建议不要母乳喂养。

 

【Tazverik包装供应/存储和处理方式】

TAZVERIK 200mg薄膜衣片为红色，圆形，双凸形，一侧凹陷有“ EZM 200”，另一侧凹陷了。 TAZVERIK可用于：

装有干燥剂的240片瓶； NDC 72607-100-00

请勿在30°C（86°F）以上的温度下存放。

 
HIGHLIGHTS OF PRESCRIBING INFORMATION 
These highlights do not include all the information needed to use 
RUKOBIA safely and effectively. See full prescribing information for 
RUKOBIA. 
x
x
QTc prolongation: Use RUKOBIA with caution in patients with a history 
of QTc prolongation or with relevant pre-existing cardiac disease or who 
are taking drugs with a known risk of Torsade de Pointes. (5.2) 
Elevations in hepatic transaminases in patients with hepatitis B or C virus 
co-infection: Elevations in hepatic transaminases were observed in a 
greater proportion of subjects with HBV and/or HCV co-infection 
compared with those with HIV mono-infection. (5.3) 
RUKOBIA (fostemsavir) extended-release tablets, for oral use 
Initial U.S. Approval: 2020 
--------------------------- INDICATIONS AND USAGE----------------------------
RUKOBIA, a human immunodeficiency virus type 1 (HIV-1) gp120-directed 
attachment inhibitor, in combination with other antiretroviral(s), is indicated 
for the treatment of HIV-1 infection in heavily treatment-experienced adults 
with multidrug-resistant HIV-1 infection failing their current antiretroviral 
regimen due to resistance, intolerance, or safety considerations. (1, 12.4) 
------------------------------ ADVERSE REACTIONS ------------------------------
The most common adverse reaction (all grades) observed in •5% of subjects 
was nausea. (6.1) 
To report SUSPECTED ADVERSE REACTIONS, contact ViiV 




-----------------------DOSAGE AND ADMINISTRATION -----------------------
One tablet taken twice daily with or without food. (2) 
------------------------------ DRUG INTERACTIONS-------------------------------
x
See full prescribing information for complete list of significant drug 
interactions. (4, 7) 
Doses of oral contraceptives should not contain more than 30 mcg of 
ethinyl estradiol per day. (7.2) 
--------------------- DOSAGE FORMS AND STRENGTHS----------------------
Extended-release tablets: 600 mg (3) 
x
------------------------------ CONTRAINDICATIONS ------------------------------
x
Hypersensitivity to fostemsavir or any of the components of the 
formulation. (4) 
Coadministration with strong cytochrome P450 (CYP)3A inducers as 
significant decreases in temsavir plasma concentrations may occur, which 
may result in loss of virologic response. (4) 
----------------------- USE IN SPECIFIC POPULATIONS -----------------------
x
Lactation: Breastfeeding is not recommended due to the potential for 
HIV-1 transmission. (8.2) 
x
See 17 for PATIENT COUNSELING INFORMATION and FDA-
approved patient labeling. 
----------------------- WARNINGS AND PRECAUTIONS------------------------
x
Immune reconstitution syndrome has been reported in patients treated 
with combination antiretroviral therapies. (5.1) 
Revised: 07/2020 
FULL PRESCRIBING INFORMATION: CONTENTS* 
1 
2 
3 
4 
5 
INDICATIONS AND USAGE 
8
USE IN SPECIFIC POPULATIONS 
DOSAGE AND ADMINISTRATION 
DOSAGE FORMS AND STRENGTHS 
CONTRAINDICATIONS 
8.1
8.2
8.4
8.5
8.6
8.7
Pregnancy 
Lactation 
Pediatric Use 
Geriatric Use 
Renal Impairment 
Hepatic Impairment 
WARNINGS AND PRECAUTIONS 
5.1
5.2
5.3
Immune Reconstitution Syndrome 
QTc Prolongation with Higher than Recommended Dosages 
Elevations in Hepatic Transaminases in Patients with 
Hepatitis B or C Virus Co-infection 
10   OVERDOSAGE 
11   DESCRIPTION 
12   CLINICAL PHARMACOLOGY 
5.4
Risk of Adverse Reactions or Loss of Virologic Response 
Due to Drug Interactions 
12.1
12.2
12.3
12.4
Mechanism of Action 
Pharmacodynamics 
Pharmacokinetics 
Microbiology 
6
7
ADVERSE REACTIONS 
6.1
Clinical Trials Experience 
DRUG INTERACTIONS 
7.1
7.2
7.3
Potential for RUKOBIA to Affect Other Drugs 
Potential for Other Drugs to Affect RUKOBIA 
Established and Other Potentially Significant Drug 
Interactions
13
NONCLINICAL TOXICOLOGY 
13.1
Carcinogenesis, Mutagenesis, Impairment of Fertility 
14   CLINICAL STUDIES 
16   HOW SUPPLIED/STORAGE AND HANDLING 
17   PATIENT COUNSELING INFORMATION 
*Sections or subsections omitted from the full prescribing information are not 
listed. 
7.4
7.5
Drugs that Prolong QT Interval 
Drugs without Clinically Significant Interactions with 
RUKOBIA 
1
Reference ID: 4635448


 
FULL PRESCRIBING INFORMATION
INDICATIONS AND USAGE
1
RUKOBIA, in combination with other antiretroviral(s), is indicated for the treatment of human
immunodeficiency virus type 1 (HIV-1) infection in heavily treatment-experienced adults with
multidrug-resistant HIV-1 infection failing their current antiretroviral regimen due to resistance,
intolerance, or safety considerations [see Clinical Studies (14)].
2
DOSAGE AND ADMINISTRATION
The recommended dosage of RUKOBIA is one 600-mg tablet taken orally twice daily with or
without food [see Clinical Pharmacology (12.3)]. Swallow tablets whole. Do not chew, crush, or
split tablets.
3
DOSAGE FORMS AND STRENGTHS
Each RUKOBIA extended-release tablet contains 600 mg of fostemsavir (equivalent to 725 mg
of fostemsavir tromethamine). The tablets are beige, oval, film-coated, biconvex tablets,
debossed with “SV 1V7” on one side.
4
CONTRAINDICATIONS
RUKOBIA is contraindicated in patients:
x    with previous hypersensitivity to fostemsavir or any of the components of RUKOBIA.
x    coadministered strong cytochrome P450 (CYP)3A inducers, as significant decreases in
temsavir (the active moiety of fostemsavir) plasma concentrations may occur which may
result in loss of virologic response. These drugs include, but are not limited to [see Drug
Interactions (7), Clinical Pharmacology (12.3)]:
o  Androgen receptor inhibitor: Enzalutamide
o  Anticonvulsants: Carbamazepine, phenytoin
o  Antimycobacterial: Rifampin
o  Antineoplastic: Mitotane
o  Herbal product: St John’s wort (Hypericum perforatum)
5
WARNINGS AND PRECAUTIONS
Immune Reconstitution Syndrome
5.1
Immune reconstitution syndrome has been reported in patients treated with combination
antiretroviral therapy, including RUKOBIA [see Adverse Reactions (6.1)]. During the initial
phase of combination antiretroviral treatment, patients whose immune systems respond may
2
Reference ID: 4635448








 
develop an inflammatory response to indolent or residual opportunistic infections (such as
Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or
tuberculosis), which may necessitate further evaluation and treatment.
Autoimmune disorders (such as Graves’ disease, polymyositis, Guillain-Barré syndrome, and
autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution;
however, the time to onset is more variable and can occur many months after initiation of
treatment.
5.2
QTc Prolongation with Higher than Recommended Dosages
RUKOBIA at 2,400 mg twice daily, 4 times the recommended daily dose, has been shown to
significantly prolong the QTc interval of the electrocardiogram [see Drug Interactions (7.4),
Clinical Pharmacology(12.2)]. RUKOBIA should be used with caution in patients with a history
of QTc interval prolongation, when coadministered with a drug with a known risk of Torsade de
Pointes, or in patients with relevant pre-existing cardiac disease. Elderly patients may be more
susceptible to drug-induced QT interval prolongation.
5.3
Elevations in Hepatic Transaminases in Patients with Hepatitis B or C Virus Co-
infection
Monitoring of liver chemistries is recommended in patients with hepatitis B and/or C co-
infection. Elevations in hepatic transaminases were observed in a greater proportion of subjects
with HBV and/or HCV co-infection compared with those with HIV mono-infection. Some of
these elevations in transaminases were consistent with hepatitis B reactivation, particularly in the
setting where anti-hepatitis therapy was withdrawn [see Adverse Reactions (6.1)]. Particular
diligence should be applied in initiating or maintaining effective hepatitis B therapy (referring to
treatment guidelines) when starting RUKOBIA in patients co-infected with hepatitis B.
5.4
Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions
The concomitant use of RUKOBIA and certain other drugs may result in known or potentially
significant drug interactions, some of which may lead to [see Contraindications (4), Warnings
and Precautions (5.2), Drug Interactions (7.3), Clinical Pharmacology (12.3)]:
x    Loss of therapeutic effect of RUKOBIA and possible development of resistance due to
reduced exposure of temsavir.
x    Possible prolongation of QTc interval from increased exposure to temsavir [see Drug
Interactions (7.4)].
See Table 3 for steps to prevent or manage these possible and known significant drug
interactions, including dosing recommendations. Consider the potential for drug interactions
prior to and during therapy with RUKOBIA, review concomitant medications during therapy
with RUKOBIA, and monitor for the adverse reactions associated with the concomitant drugs.
3
Reference ID: 4635448








 
6
ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of the labeling:
x    Immune reconstitution syndrome [see Warnings and Precautions (5.1)].
x    QTc prolongation [see Warnings and Precautions (5.2)].
x    Elevations in hepatic transaminases in patients with hepatitis B or C virus co-infection  [see
Warnings and Precautions (5.3)].
6.1
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of a drug cannot be directly compared with rates in the clinical
trials of another drug and may not reflect the rates observed in practice.
A total of 620 subjects with HIV-1 infection received at least one dose of RUKOBIA as part of a
controlled clinical trial.
The primary safety assessment of RUKOBIA is based on 96 weeks of data from a Phase 3
partially randomized, international, multicenter, double-blind, placebo-controlled trial
(BRIGHTE) conducted in 371 heavily treatment-experienced adult subjects [see Clinical Studies
(14)]. In the randomized cohort, 203 subjects received at least one dose of blinded RUKOBIA
600 mg twice daily and 69 subjects received placebo in addition to their current failing regimen
for 8 days of functional monotherapy. Beyond Day 8, all randomized subjects except one
received open-label RUKOBIA 600 mg twice daily plus an optimized background therapy
(OBT). In the nonrandomized cohort, 99 subjects received open-label RUKOBIA 600 mg twice
daily plus OBT from Day 1 onward.
A total of 370 subjects (271 randomized and 99 nonrandomized) received at least 1 dose of
RUKOBIA 600 mg twice daily in the BRIGHTE trial. Overall, most (81%) of the adverse
reactions reported with RUKOBIA were mild or moderate in severity. The proportion of subjects
who discontinued treatment with RUKOBIA due to an adverse event was 7% at Week 96
(randomized: 5% and nonrandomized: 12%). The most common adverse events leading to
discontinuation were related to infections (3% of subjects receiving RUKOBIA). Serious drug
reactions occurred in 3% of subjects and included 3 cases of severe immune reconstitution
inflammatory syndrome.
Data from the randomized cohort form the basis of the safety assessment of RUKOBIA because
the presence of significant comorbid illness in the nonrandomized cohort (associated with
advanced HIV infection) may confound the assessment of causality. Adverse reactions (all


JUDGHVUHSRUWHGLQ•RIsubjects in the randomized cohort in the Week 96 analysis are listed
in Table 1.
4
Reference ID: 4635448








 
Table 1. Adverse Reactions  (Grades 1 to 4) Reported in •2% of Subjects Receiving
a 
RUKOBIA plus OBT in the BRIGHTE Trial, Randomized Cohort (Week 96 Analysis)
RUKOBIA plus OBT
Adverse Reaction
(n = 271)
b 
10%
4%
Nausea
Diarrhea
Headache
Abdominal pain
Dyspepsia
4%
c 
3%
3%
Fatigue
d 
3%
Rash
e 
3%
Sleep disturbance
f 
3%
Immune Reconstitution Inflammatory Syndrome
2%
Somnolence
Vomiting
2%
2%
a 
Frequencies of adverse reactions are based on all treatment-emergent adverse events attributed
to study drug by the investigator.
b 
Of the 272 subjects enrolled in the randomized cohort, 1 subject who received placebo
withdrew from the trial prior to receiving RUKOBIA in the open-label phase of the trial.
Includes pooled terms: abdominal discomfort, abdominal pain, and abdominal pain upper.
Includes pooled terms: fatigue and asthenia.
Includes pooled terms: rash, rash generalized, rash maculo-papular, rash pruritic, and dermatitis
allergic.
c 
d 
e 
f 
Includes pooled terms: insomnia, sleep deficit, sleep disorder, abnormal dreams.
Adverse reactions in the nonrandomized cohort were similar to those observed in the randomized
cohort. The most common adverse reactions reported in nonrandomized subjects were fatigue
(7%), nausea (6%), and diarrhea (6%).
Less Common Adverse Reactions
The following adverse reactions occurred in <2% of subjects receiving RUKOBIA in the
randomized cohort of the BRIGHTE trial. These events have been included based on the
assessment of potential causal relationship and were also reported in the nonrandomized cohort.
Cardiac Disorders: Electrocardiogram QT prolonged. All reports were asymptomatic.
Musculoskeletal Disorders:  Myalgia.
Nervous System Disorders: Dizziness, dysgeusia, neuropathy peripheral (includes pooled terms:
neuropathy peripheral and peripheral sensory neuropathy).
Skin and Subcutaneous Tissue Disorders:  Pruritus.
5
Reference ID: 4635448


 
Laboratory Abnormalities
Selected laboratory abnormalities (Grades 3 to 4) with a worsening grade from baseline and
representing the worst-grade toxicity in •2% of subjects in the randomized cohort of the
BRIGHTE trial are presented in Table 2.
Table 2. Selected Laboratory Abnormalities (Grades 3 to 4) Reported in  •RI
Subjects in the Randomized Cohort Receiving RUKOBIA plus OBT in the BRIGHTE
Trial (Week 96 Analysis)
Laboratory Parameter
Preferred Term
RUKOBIA plus OBT
a
(n = 271 )
5%
ALT (>5.0 x ULN)
AST (>5.0 x ULN)
4%
Direct bilirubin (>ULN)
Bilirubin •x ULN)
b 
7%
3%
Cholesterol 

 classes of antiretroviral medications remaining at baseline due to resistance, intolerability,
contraindication, or other safety concerns. Subjects were enrolled in either a randomized or
nonrandomized cohort defined as follows:
x    Within the randomized cohort (n = 272), subjects had 1, but no more than 2, fully active and
available antiretroviral agent(s) at screening which could be combined as part of an
efficacious background regimen. Randomized subjects received either blinded RUKOBIA
600 mg twice daily (n = 203) or placebo (n = 69) in addition to their current failing regimen
for 8 days of functional monotherapy. Beyond Day 8, randomized subjects received open-
label RUKOBIA 600 mg twice daily plus an investigator-selected OBT. This cohort provides
primary evidence of efficacy of RUKOBIA.
x    Within the nonrandomized cohort (n = 99), subjects had no fully active and approved
antiretroviral agent(s) available at screening. Nonrandomized subjects were treated with
23
Reference ID: 4635448


 
open-label RUKOBIA 600 mg twice daily plus OBT from Day 1 onward. The use of an
investigational drug(s) as a component of the OBT was permitted in the nonrandomized
cohort.
Overall, the majority of subjects were male (78%), white (70%), and the median age was 49
years (range: 17 to 73 years). At baseline, the median HIV-1 RNA was 4.6 log10 copies/mL and
the median CD4+ cell count was 80 cells/mm
nonrandomized subjects, respectively). Seventy-five percent (75%) of all treated subjects had a
CD4+ cell count <200 cells/mm  at baseline (with 30% <20 cells/mm  ). Overall, 86% had a
(100 and 41 cells/mm  for randomized and
3                                                      3 
3 
3
history of Acquired Immune Deficiency Syndrome (AIDS) and 8% had a history of hepatitis B
and/or C virus co-infection at baseline. Seventy one percent (71%) of subjects had been treated
for HIV for >15 years; 85% had been exposed to •5 different HIV treatment regimens upon
entry into the trial.
Fifty-two percent (52%) of subjects in the randomized cohort had 1 fully active agent within
their initial failing background regimen, 42% had 2, and 6% had no fully active agent. Within the
nonrandomized cohort, 81% of subjects had no fully active agent(s) in their original regimen and
19% had 1 fully active agent, including 15% (n = 15) who received ibalizumab, which was an
investigational agent at the time of the BRIGHTE trial start-up.
Randomized Cohort
The primary efficacy endpoint was the adjusted mean decline in HIV-1 RNA from Day 1 to
Day 8 with RUKOBIA versus placebo in the randomized cohort. The results of the primary
endpoint analysis demonstrated superiority of RUKOBIA compared with placebo, as shown in
Table 11.
Table 11. Plasma HIV-1 RNA Log10 (copies/mL) Change from Day 1 to Day 8
(Randomized Cohort) in BRIGHTE Trial – ITT-E Population
RUKOBIA
600 mg Twice Daily
a
(n = 201 )
Placebo
(n = 69)
-0.166
Adjusted Mean
b 
(95% CI)
-0.791
(-0.885, -0.698)
-0.625
(-0.326, -0.007)
-
Difference
c 
(95% CI)
(-0.810, -0.441)
d 
a 
Two subjects who received RUKOBIA with missing Day 1 HIV-1 RNA values were not
included in the analysis.
b 
c 
d 
Mean adjusted by Day 1 log10 HIV-1 RNA.
Difference: RUKOBIA minus placebo.
P-value <0.0001 for the adjusted and unadjusted mean difference of viral load change from
baseline for RUKOBIA compared with placebo.
24
Reference ID: 4635448


 
At Day 8, 65% (131/203) and 46% (93/203) of subjects who received RUKOBIA had a
reduction in viral load from baseline >0.5 log10 copies/mL and >1 log10 copies/mL,  respectively,
compared with 19% (13/69) and 10% (7/69) of subjects, respectively, in the placebo group.
By subgroup analysis, randomized subjects who received RUKOBIA with baseline HIV-1 RNA
>1,000 copies/mL achieved a mean decline in viral load of 0.86 log10 copies/mL at Day 8
compared with 0.20 log10 copies/mL in subjects treated with blinded placebo. Subjects with
baseline HIV-1 RNA ”1,000 copies/mL achieved a mean decline in viral load of 0.22 log10 
copies/mL at Day 8 compared with a mean increase of 0.10 log10 copies/mL in subjects treated
with blinded placebo.
Virologic outcomes by ITT-E Snapshot Analysis at Weeks 24 and 96 in the BRIGHTE trial
are shown in Table 12 and Table 13 for the randomized cohort. There was considerable
variability in the number of antiretrovirals (fully active and otherwise) included in OBT
regimens. The majority of subjects (84%) received dolutegravir as a component of OBT, of
which approximately half (51% overall) also received darunavir with ritonavir or cobicistat.
Virologic outcomes by ITT-E Snapshot Analysis at Week 48 were consistent with those
observed at Week 24.
Table 12. Virologic Outcomes (HIV-1 RNA <40 copies/mL) at Weeks 24 and 96 with
RUKOBIA (600 mg Twice Daily) plus OBT (Randomized Cohort) in BRIGHTE Trial
(ITT-E Population, Snapshot Algorithm)
RUKOBIA 600 mg Twice Daily plus OBT
Week 24
(n = 272)
53%
Week 96
(n = 272)
60%
HIV-1 RNA <40 copies/mL
HIV-51$•