Drugs

Drug Trials Snapshots: PIFELTRO

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.

LIMITATIONS OF THIS SNAPSHOT:
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 PIFELTRO Prescribing Information for complete information.

PIFELTRO (doravirine)
pih-FEL-tro
Merck Sharp & Dohme Corp.
Approval date: August 30, 2018


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

PIFELTRO is a drug for the treatment of human immunodeficiency virus-1 (HIV-1) infection in adults who have not taken HIV-1 medicines before.

HIV-1 is the virus that causes acquired immune deficiency syndrome (AIDS).

How is this drug used?

PIFELTRO is a tablet that is taken by mouth once a day in combination with other drugs approved for the treatment of HIV-1 infection.

Use of PIFELTRO with some common medicines is prohibited because of interactions that affect PILFETRO’s benefit.

What are the benefits of this drug?

PIFELTRO reduced viral load of HIV-1 and is comparable to other approved drugs for treatment of HIV-1 infection.

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

The table below summarizes the primary efficacy endpoint (virologic outcomes) at Week 48 for the two clinical trials of treatment-naïve adults.

Table 2. Virologic Outcomes in Trial 1 and Trial 2 at Week 48 in HIV-1 Adults with No Antiviral Treatment History

OutcomeTrial 1Trial 2
PIFELTRO +
2 NRTIs
DRV+r
+ 2 NRTIs
DELSTRIGOEFV/FTC/TDF
N=383N=383N=364N=364
HIV-1 RNA <50 copies/mL84%80%84%81%
Treatment Differences (95% CI) *3.9% (-1.6%, 9.4%)3.5% (-2.0%, 9.0%)

*The 95% CIs for the treatment differences were calculated using stratum-adjusted Mantel-Haenszel method.
Note: NRTIs = FTC/3TC or ABC/3TC
NRTI=nucleoside reverse transcriptase inhibitor
DVR+r= darunavir+ ritonavir; FTC=emtricitabine; 3TC=lamivudine; ABC=abacavir; EFV=efavirenz; TDF=tenofovir disoproxil fumarate

PIFELTRO Prescribing Information

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

  • Sex: PIFELTRO worked similarly in men and women.
  • Race: PIFELTRO worked similarly in all races.
  • Age: The majority of patients in the trials were below 65 years of age. Differences in how well PIFELTRO worked between those below and 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?

Subgroup analyses based on HIV-1 RNA <50 copies/mL at Week 48 are presented below.

Table 3. Proportion (%) of Subjects With HIV-1 RNA <50 copies/mL at Week 48 by Demographic Category

Demographic SubgroupTrial 1Trial 2
PIFELTRO +
2 NRTIs
DRV+r
+ 2 NRTIs
DELSTRIGOEFV/FTC/TDF
N=383N=383N=364N=364
Sex
Men84%
(n = 319)
82%
(n = 326)
84%
(n = 305)
80%
(n = 311)
Women81%
(n = 64)
67%
(n = 57)
85%
(n = 59)
83%
(n = 53)
Race
White87%
(n = 280)
83%
(n = 280)
84%
(n = 177)
81%
(n = 170)
Non-White75%
(n = 103)
72%
(n = 103)
84%
(n = 187)
80%
(n = 194)
Age Group
<65 years84%
(n=381)
80%
(n=379)
84%
(n=362)
81%
(n=362)
≥ 65 years100%
(n=2)
75%
(n=4)
100%
(n=2)
50%
(n=2)
Ethnicity
Hispanic or Latino88%
(n = 93)
81%
(n = 86)
83%
(n = 126)
84%
(n = 120)
Not Hispanic or Latino82%
(n = 284)
79%
(n = 290)
85%
(n = 236)
79%
(n = 238)

Note: NRTIs = FTC/3TC or ABC/3TC.

FDA Review

What are the possible side effects?

PIFELTRO may cause a serious condition called immune reconstitution syndrome, similar to other approved drugs for treatment of HIV-1 infection. This condition can happen at the beginning of HIV-1 treatment when the immune system may get stronger and begin to fight infections that have been hidden in the body for a long time.

The most common side effects associated with PIFELTRO are nausea, dizziness, headache, fatigue, diarrhea, abdominal pain, and abnormal dreams.

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

The table below summarizes adverse reactions reported in greater than or equal to 5% of patients in any treatment group from these 2 trials.

Table 4: Adverse Reactions* (All Grades) Reported in >5%† of Subjects in Any Treatment Group in Adults with No Antiretroviral Treatment History in Trial 1 and Trial (Week 48)

 Trial 1Trial 2
PIFELTRO+2 NRTIs
N=383
DRV+r+2 NRTIs‡
N=383
DELSTRIGO
N=364
EFV/FTC/TDF
N=364
Nausea7%8%5%7%
Headache6%3%4%4%
Fatigue6%3%4%4%
Diarrhea5%13%3%5%
Abdominal Pain5%2%1%2%
Dizziness3%2%7%32%
Rash2%3%2%12%
Abnormal Dreams1%<1%5%9%
Insomnia1%2%4%5%
Somnolence0%<1%3%7%

*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 (moderate or severe) occurred in ≥ 2% of subjects treated with doravirine.
NRTI = nucleoside reverse transcriptase inhibitor.
NRTIs = FTC/TDF or ABC/3TC.
Fatigue: includes fatigue, asthenia, malaise
Abdominal Pain: includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, epigastric discomfort
Rash: includes rash, rash erythematous, rash generalized, rash macular, rash maculo-papular, rash papular, rash pruritic, rash pustular

PIFELTRO Prescribing Information

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

  • Sex: The risk of side effects was similar in men and women.
  • Race: The risk of side effects was similar in all races.
  • Age: The majority of patients in the trials were below 65 years of age. Differences in the risk of side effects between those below and above 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?

The table below summarizes the occurrence of treatment-emergent adverse events (TEAEs) by subgroups in each trial from 0-48 weeks.

Table 5. Treatment-Emergent Adverse Events (TEAE) by Demographic Subgroups

 Trial 1Trial 2
PIFELTRO+2 NRTIs
n/N (%)
DRV+r+2 NRTIs
n/N (%)
DELSTRIGO
n/N (%)
EFV/FTC/TDF
n/N (%)
Overall TEAEs307/383 (80.2)300/383 (78.3)301/364 (82.7)330/364 (90.7)
Sex
Men258/319 (80.9)256/326 (78.5)255/305 (83.6)283/311 (91)
Women49/64 (76.6)44/57 (77.2)46/59 (78)47/53 (88.7)
Race
White228/280 (81.4)217/280 (77.5)150/177 (84.7)155/170 (91.2)
Black or
African
American
65/86 (75.6)69/88 (78.4)53/67 (79.1)58/68 (85.3)
Asian6/7 (85.7)7/7 (100)45/59 (76.3)60/65 (92.3)
Age Group
<65 years305/381 (80.1)296/379 (78.1)301/362 (83.1)328/362 (90.6)
≥65 years2/2 (100)4/4 (100)0/2 (0)2/2 (100)

Clinical Trial Data

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved PIFELTRO based primarily on evidence from 2 clinical trials (Trial 1/ NCT02275780 and Trial 2/NCT02403674) of 1,494 adults with HIV-1 infection who have not received any prior treatments for the infection.

Trials were conducted in the United States,Canada, Europe, Asia, Africa and Latin America.

Figure 1 summarizes how many men and women were in the clinical trials.

Figure 1. Baseline Demographics by Sex

Pie chart summarizing how many men and women were in the clinical trials. In total, 1261 men (84%) and 233 women (16%) participated in the clinical trials.

FDA Review

Figure 2 and Table 1 summarize the percentage of patients by race in the clinical trials.

Figure 2. Baseline Demographics by Race

Pie chart summarizing the percentage of patients by race enrolled in the clinical trials. In total, 907 Whites (61%), 309 Black or African Americans (21%), 138 Asians (9%)  and 140 all Other (9%) participated in the clinical trials.

FDA Review

Table 1. Baseline Demographics by Race

RaceNumber of PatientsPercentage of Patients
White90761
Black or African American30921
Asian1389
American Indian or Alaska Native221
Native Hawaiian or Other Pacific Islander3less than 1
Other1157

FDA Review

Figure 3 summarizes patients by age in the clinical trials.

Figure 3. Baseline Demographics by Age

Pie chart summarizing how many individuals of certain age groups were in the clinical trials. In total, 1484 patients were less than 65 years old (99%) and 10 were 65 and older (1%).

FDA Review

Who participated in the trials?

The table below summarizes baseline demographics for two clinical trials.

Table 6. Baseline Demographics in Trials 1 and 2

Demographic CategoryTRIAL 1
N=766
Trial 2
N=728
TOTAL
N=1494
Sex
Men645 (84.2)616 (84.6)1261 (84.4)
Women121 (15.8)112 (15.4)233 (15.6)
Race
White560 (73.1)347 (47.7)907 (60.7)
Black or African
American
174 (22.7)135 (18.5)309 (20.7)
Asian14 (1.8)124 (17)138 (9.2)
American Indian or
Alaska Native
6 (0.8)16 (2.2)22 (1.5)
Native Hawaiian or
Other Pacific Islander
3 (0.4)03 (0.2)
Other9 (1.2)106 (14.6)115 (7.7)
Age (years)
Min, max18, 6918, 7018,70
Age Group 
< 65 years760 (99.2)724 (99.5)1484 (99.3)
≥ 65 years6 (0.8)4 (0.5)10 (0.7)
Ethnicity
Hispanic or Latino179 (23.4)246 (33.8)425 (28.4)
Not Hispanic or Latino574 (74.9)474 (65.1)1048 (70.1)
Not Reported or
Unknown
13 (1.7)8 (1.1)21 (1.4)
Region
United States266 (34.7)175 (24.1)441 (29.5)
Canada20 (2.6)10 (1.1)
7 (1.9%)
30 (2)
Latin America71 (9.3)176 (24.2)247 (16.5)
Europe349 (45.6)182 (25.0)531 (35.5)
Asia/Pacific15 (2.0)121 (16.6)136 (9.1)
Africa45 (5.9)64 (8.8)109 (7.3)

Adapted from FDA Review

How were the trials designed?

PIFELTRO was evaluated in two clinical trials of adults with HIV-1 infection who have not taken medicines to treat the infection before. Both trials compared PIFELTRO to other medicines for HIV-1 infection.

In Trial 1, patients were randomized to either PIFELTRO once daily or darunavir + ritonavir once daily. Both groups also received either emtricitabine/ tenofovir disoproxil fumarate or abacavir/lamivudine based on the investigator’s decision.

In Trial 2, patients were randomized to either fixed combination of PIFELTRO/ lamivudine / tenofovir disoproxil fumarate (called DELSTRIGO)* or efavirenez/ emtricitabine / tenofovir disoproxil fumarate once daily.

The benefit of PIFELTRO was assessed 48 weeks later by comparing it to other medicines. The measure of benefit was a proportion of patients who decreased the HIV-1 viral load in the blood to less than 50 copies/mL.

*DELSTRIGO was developed as a complete regimen for the treatment of HIV-1 infection.

How were the trials designed?

FDA approved PIFELTRO based primarily on data from two randomized, multicenter, double-blind, active controlled Phase 3 trials in HIV-1 infected patients with no antiretroviral treatment history.

In Trial 1, patients were randomized to either PIFELTRO once daily or darunavir 800 mg + ritonavir 100 mg (DRV+r) once daily each in combination with emtricitabine/tenofovir DF (FTC/TDF) or abacavir/lamivudine (ABC/3TC) selected by the investigator.

In Trial 2, patients were randomized to either fixed combination of doravirine/3TC/TDF or EFV 600 mg/FTC 200 mg/TDF 300 mg once daily.

Primary efficacy outcome was the proportion of patients with HIV-1 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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Page Last Updated: 09/13/2018
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