Drugs

Drug Trial Snapshot: TPOXX

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights subjects who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among these subjects when grouped by sex, race, and age. The efficacy of this drug was studied in animal models while the safety was studied in healthy human volunteers. 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 TPOXX Prescribing Information for complete information.

TPOXX (tecovirimat)
(Tee-pahx)
SIGA Technologies
Approval date: July 13, 2018


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

TPOXX is a drug for the treatment of smallpox disease.

Smallpox is a serious and highly contagious viral disease that causes fever, rash and deep skin scars and may progress to death. No cases of naturally occurring smallpox disease have happened since the late 1970s because worldwide vaccination led to the eradication of smallpox.

How is this drug used?

TPOXX is taken twice daily for 14 days. The number of capsules per day depends on patient’s weight.

What are the benefits of this drug?

More animals treated with TPOXX lived compared to the animals treated with placebo. Because smallpox disease has been eradicated from the world and it is not feasible or ethical to conduct efficacy trials in humans, the efficacy of TPOXX could not be studied in patients.

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

The efficacy of TPOXX for the treatment of smallpox is based on studies in monkeys (cynomolgus macaques) and New Zealand White (NZW) rabbits. The primary efficacy endpoint was proportion of infected animals that survived to the pre-specified end-of-study.

It was not possible to conduct controlled clinical trials in humans with smallpox because this disease is eradicated.

Table 2. Survival Rates in TPOXX Treatment Studies in Cynomolgus Macaques and NZW Rabbits Exhibiting Clinical Signs of Orthopoxvirus Disease

 

Treatment Initiationa

Survival Percentage
(# survived/n)

p-valueb

Survival Rate Differencec
(95% CI)d

Placebo

TPOXX

Cynomolgus Macaques

Study 1

Day 4

0% (0/7)

80% (4/5)

0.0038

80% (20.8%, 99.5%)

Study 2

Day 4

0% (0/6)

100% (6/6)

0.0002

100% (47.1%, 100%)

Study 3

Day 4

0% (0/3)

83% (5/6)

0.0151

83% (7.5%, 99.6%)

Day 5

83% (5/6)

0.0151

83% (7.5%, 99.6%)

Day 6

50% (3/6)

0.1231

50% (-28.3%, 90.2%)

NZW Rabbits

Study 4

Day 4

0% (0/10)

90% (9/10)

< 0.0001

90% (50.3%, 99.8%)

Study 5

Day 4

NAe

88% (7/8)

NA

NA

aDay post-challenge tecovirimat treatment was initiated
bp-value is from 1-sided Boschloo Test (with Berger-Boos modification of gamma = 0.000001) compared to placebo
cSurvival percentage in tecovirimat treated animals minus survival percentage in placebo treated animals
dExact 95% confidence interval based on the score statistic of difference in survival rates
eA placebo control group was not included in this study.
NA = Not Applicable
 

TPOXX Prescribing Information

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

The efficacy of TPOXX has been studied only in animals, so the differences among patients grouped by sex, race, and age could not be assessed.

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

Due to smallpox disease eradication and ethical considerations, clinical efficacy trials for TPOXX were not conducted in humans. Therefore, human data on efficacy and subgroup analyses are not available.

What are the possible side effects?

The side effects of TPOXX have been studied in healthy human volunteers.

TPOXX may cause lowering of blood sugar levels when co-administered with blood glucose-lowering drug repaglinide.

The most common side effects of TPOXX are headache, nausea, abdominal pain, and vomiting.

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

The table below summarizes adverse reactions that occurred in at least 2% of participants in the TPOXX treatment group.

Table 3. Adverse Reactions Reported in ≥ 2% of Healthy Adults Receiving at Least One Dose of TPOXX 600 mg

Adverse Reaction

TPOXX
N = 359
(%)

Placebo
N = 90
(%)

Headache

12

8

Nausea

5

4

Abdominal paina

2

1

Vomiting

2

0

aIncludes abdominal pain, abdominal pain upper, abdominal distension, abdominal discomfort, abdominal pain lower, epigastric pain

TPOXX 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 between White and Black participants. Differences among other races could not be determined due to the small number of participants.
  • Age: Most participants in the clinical trial were younger than 65 years of age, so differences in the occurrence of side effects between participants 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 shows the incidence of treatment-emergent adverse events (TEAEs) by subgroup.

Table 4. Subgroup Analysis of TEAEs

Subgroup

TPOXX (N=359)

Placebo (N=90)

n (%)

Total
number of patients (N)

 

n (%)

Total
number of patients (N)

Overall/All participants

134 (37.3)

359

30 (33.3)

90

Sex

   Male

48 (32.4)

148

9 (25)

36

   Female

89 (42.1)

211

21(38.8)

54

Race

 

   White and Other

105 (42.1)

249

17 (27.4)

62

   Black or African American

25 (24.7)

101

12 (46.1)

26

   All   Other

4 (44.4)

9

1 (50)

2

Age Group

   18-65 years

118 (36.5)

323

26 (32.9)

79

   ≥65 years

16 (44.4)

36

4 (36.4)

11

Clinical trial data

WHO WAS IN THE STUDIES?

Who participated in the clinical trials?

The FDA approved TPOXX based on efficacy results from animal studies and safety results from one clinical trial. The clinical trial enrolled 449 heathy adults and was conducted at 12 sites in the United States.

The figure below summarizes how many men and women were in the clinical trial that evaluated TPOXX safety.

Figure 1. Baseline Demographics by Sex

Pie chart summarizing how many men and women were in the clinical trials. In total, 184 men (41%) and 265 women (59%) participated in the clinical.

FDA Review

Figure 2 and Table 1 below summarize healthy participants by race who participated in the clinical trial that evaluated TPOXX safety.

Figure 2. Baseline Demographics by Race

Pie chart summarizing the percentage of patients by race enrolled in the clinical trial. In total, 311 White (69%), 127  Black or African American (28%), 4 Asian (1%), and 7 Other (2%), participants were in the clinical Trial FDA Review

Table 1. Baseline Demographics by Race

Race

Number of Participants

Percentage

White

311

69

Black or African American

127

28

Asian

4

1

Other

7

2

FDA Review

Figure 3 summarizes the percentage of healthy participants by age group who participated in the clinical trial that evaluated TPOXX safety.

Figure 3. Baseline Demographics by Age

Pie charts summarizing how many individuals of certain age groups were enrolled in the clinical trial. In total, 402 participants were less than 65 years old (90%) and 47 participants were 65 years and older (10%).

FDA Review

The table below summarizes demographics of participants in the clinical trial.

Table 5. Baseline Demographics of Healthy Participants in the Safety Clinical Trials

Demographic Parameters

TPOXX
(N=359)
n (%)

Placebo
 (N=90)
n (%)

Total
(N=449)
n (%)

Sex

Men

148 (41%)

36 (40%)

184 (41%)

Women

211 (59%)

54 (60%)

265 (59%)

Race

White

249 (69%)

62 (69%)

311 (69%)

Black or African American

101 (28%)

26 (29%)

127 (28%)

Asian

3 (1%)

1 (1%)

4 (1%)

Other1

6 (2%)

1 (1%)

7 (2%)

Age

Mean years (SD)

40 (15.7)

42 (15.9)

41 (15.7)

Median (years)

38

41

39

Min, max (years)

18, 79

18, 80

18, 80

Age Group

 < 65 years

323 (90%)

79 (88%)

402 (90%)

≥ 65 years

36 (10%)

11 (12%)

47 (10%)

Ethnicity

Hispanic or Latino

43 (12%)

5 (6%)

48 (11%)

Non-Hispanic or Latino

315 (88%)

85 (94%)

400 (89%)

Not disclosed

1 (<1%)

0

1 (<1%)

Geographic location

US

359 (100%)

90 (100%)

449 (100%)

Rest of the world

0

0

0

1Includes American Indian/Alaska Native, Hawaiian or Pacific Islander and other

FDA Review

How were the trials designed?

The efficacy of TPOXX was evaluated in animal studies. The side effects of TPOXX were evaluated in one clinical trial of healthy participants. Participants received either TPOXX or placebo twice a day for 14 days. Neither the participant nor the health care providers knew which treatment was given until after the trial was completed.

How were the trials designed?

The efficacy of TPOXX for the treatment of smallpox was studied in cynomolgus macaques and NZW rabbits. The animal efficacy studies were conducted under varying conditions and compared survival rates in TPOXX and placebo treated groups.

The safety of TPOXX was studied in one randomized, double-blind, placebo-controlled clinical trial of healthy participants who were treated with TPOXX or placebo twice daily for 14 days.

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

Back to Drug Trials Snapshots

Page Last Updated: 07/17/2018
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