Drug Trials Snapshot: ANTHIM
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 ANTHIM Prescribing Information for complete information.
ANTHIM (obiltoxaximab)
(ˈan(t)-thim)
Elusys Therapeutics, Inc
Approval date: March 18, 2016
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
ANTHIM is a drug for the treatment of inhalational anthrax. It is meant to be used together with an appropriate antibiotic.
ANTHIM can also be used to prevent inhalational anthrax when there are no other treatment options.
Inhalational anthrax is a rare and serious bacterial disease that can cause massive and irreversible tissue injury, shock and death.
How is this drug used?
ANTHIM is given by a healthcare provider through a vein (IV or intravenous infusion) over about 1 hour and 30 minutes.
What are the benefits of this drug?
ANTHIM improved survival in the studies done on animals with inhalational anthrax. Because inhalational anthrax is very rare, the efficacy of ANTHIM could not be studied in human patients.
What are the benefits of this drug (results of trials used to assess efficacy)?
The efficacy of ANTHIM for the treatment of inhalational anthrax is based on studies in New Zealand White (NZW) rabbits and monkeys (cynomolgus macaques). More animals survived in the group treated with ANTHIM compared to the placebo group. It was not possible to conduct controlled clinical trials in humans with inhalational anthrax, because this infection is very rare.
Table 2. Survival Proportions in Monotherapy Treatment Studies of ANTHIM 16 mg/kg IV in All Randomized Animals Positive for Bacteremia Prior to Treatment
| Proportion of Survival at Day 281 (# survived/n) | p-value2 | 95% CI3 | ||
|---|---|---|---|---|
| Placebo | ANTHIM 16 mg/kg IV | |||
| NZW* Rabbits | ||||
| Study 1 | 0% (0/9) | 93% (13/14) | 0.0010 | (0.59, 1.00) |
| Study 2 | 0 % (0/13) | 62% (8/13) | 0.0013 | (0.29, 0.86) |
| Cynomolgus Macaques | ||||
| Study 3 | 6 % (1/16) | 47% (7/15) | 0.0068 | (0.09, 0.68) |
| Study 44 | 0 % (0/17) | 31% (5/16) 35% (6/17) | 0.0085 0.0055 | (0.08, 0.59) (0.11, 0.62) |
1Survival assessed 28 days after spore challenge
2p-value is from 1-sided Boschloo Test (with Berger-Boos modification of gamma=0.001) compared to placebo
3Exact 95% confidence interval of difference in survival rates
4ANTHIM products manufactured at two different facilities were tested in two separate treatment arms.
*New Zealand White
ANTHIM Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
The efficacy of ANTHIM has been studied only in animals, so the differences among subjects grouped by sex, race, and age could not be determined.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Due to ethical considerations, clinical efficacy trials for ANTHIM 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 ANTHIM have been studied in healthy human volunteers.
ANTHIM may cause serious allergic reactions including a life threatening reaction called anaphylaxis.
Other common side effects of ANTHIM are headache, itching, upper respiratory tract infections, cough, IV site bruising, swelling, and pain, stuffy nose (nasal congestion), rash, and pain in a limb.
What are the possible side effects (results of trials used to assess safety)?
Hypersensitivity reactions were the most common adverse reactions seen in 34 (10%) of the healthy humans who received Anthim; these reactions included pruritus, urticaria, cough and anaphylaxis. The table below summarizes adverse reactions that occurred in ≥ 1.5% of healthy human participants receiving a single dose of ANTHIM (16 mg/kg IV) and more frequently than those receiving placebo.
Table 3. Adverse Reactions Reported in ≥ 1.5% of Healthy Adult Participants Exposed to Single Dose ANTHIM 16 mg/kg IV
| Adverse Reactions | Placebo N =70 (%) | Single Dose ANTHIM N = 300* (%) |
|---|---|---|
| Headache | 4 (6%) | 24 (8%) |
| Pruritus | 1 (1%) | 11 (4%) |
| Infections of the upper respiratory tract | 2 (3%) | 14 (5%) |
| Cough | 0 | 9 (3%) |
| Vessel puncture site bruise | 1 (1%) | 8 (3%) |
| Infusion site swelling | 1 (1%) | 8 (3%) |
| Nasal congestion | 1 (1%) | 5 (2%) |
| Infusion site pain | 0 | 7 (2%) |
| Urticaria | 0 | 5 (2%) |
| Pain in extremity | 1 (1%) | 5 (2%) |
+ 20 participants in the ANTHIM alone treatment arm of study 3
ANTHIM 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 trials were younger than 65 years of age, so differences in the occurrence of side effects between groups of 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 | ANTHIM single dose (n=300) | Placebo (n=70) | ||
|---|---|---|---|---|
| n (%) | Total number of patients (n) | n (%) | Total number of patients (n) | |
| Overall/All participants | 138 (46%) | 300 | 27 (40%) | 70 |
| Sex | ||||
| Male | 72 (44%) | 162 | 12 (32%) | 38 |
| Female | 66 (48%) | 138 | 15 (47%) | 32 |
| Age Group | ||||
| 18-65 years | 119 (44%) | 270 | 25 (38%) | 66 |
| 65 years and older | 19 (63%) | 30 | 2 (50%) | 4 |
| Race | ||||
| White | 104 (50%) | 210 | 21 (48%) | 44 |
| Black or African American | 29 (36%) | 80 | 5 (22%) | 23 |
| Asian | 1 (33%) | 3 | 1 (50%) | 2 |
| American Indian or Alaska Native | 2 (67%) | 3 | 0 | 0 |
| Other | 2 (50%) | 4 | 0 | 1 |
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved ANTHIM based on efficacy results from animal studies and safety results from three human clinical trials. The clinical trials enrolled 370 heathy participants and were conducted in the United States.
The figure below summarizes how many men and women were in the clinical trials that evaluated ANTHIM safety.
Figure 1. Baseline Demographics by Sex
Figure 2 and Table 1 below summarize healthy participants by race were in the clinical trials that evaluated ANTHIM safety.
Figure 2. Baseline Demographics by Race
Table 1. Baseline Demographics by Race
| Race | Number of Participants | Percentage |
|---|---|---|
| White | 254 | 69% |
| Black or African American | 103 | 28% |
| Asian | 5 | 1% |
| American Indian or Alaska Native | 3 | 1% |
| Other | 5 | 1% |
Clinical trial data
Figure 3 summarizes the percentage of healthy participants by age group who were in the clinical trials that evaluated ANTHIM safety.
Figure 3. Baseline Demographics by Age
Who participated in the trials?
The table below summarizes demographics of participants in the clinical trials.
Table 5. Baseline Demographics of Healthy Participants in the Safety Clinical Trials
| Demographic Parameters | Placebo (N=70) n (%) | ANTHIM (N=300) n (%) | Total (N=370) n (%) |
|---|---|---|---|
| Sex | |||
| Male | 38 (54) | 162 (54) | 200 (54) |
| Female | 32 (46) | 138 (46) | 170 (46) |
| Age | |||
| Mean years | 41.5 | 41.9 | 41.7 |
| Median (years) | 40 | 42 | 41 |
| Min, Max (years) | 20,78 | 18,79 | 18,79 |
| Age Group (years) | |||
| ≥18 - > | 66 (94) | 270 (90) | 336(91) |
| ≥65 | 4 (6) | 30 (10) | 34 (9) |
| Race | |||
| White | 44 (63) | 210 (70) | 254(69) |
| Black or African American | 23 (33) | 80 (27) | 103(28) |
| Asian | 2 (3) | 3 (1) | 5 (1) |
| American Indian or Alaska Native | 0 | 3 (1) | 3(1) |
| Other | 1 (1) | 4 (1) | 5 (1) |
| Ethnicity | |||
| Hispanic or Latino | 9 (13) | 26 (8) | 35(9) |
| Not Hispanic or Latino | 61 (87) | 274 (91) | 335 (91) |
How were the trials designed?
The efficacy of ANTHIM was evaluated in rabbits and monkeys. The side effects of ANTHIM were evaluated in the three clinical trials of healthy participants. Most participants received one or more treatments with ANTHIM, while the rest of the participants received placebo. Neither the participant nor the health care providers knew which treatment was given until after the trials were completed.
How were the trials designed?
The efficacy of ANTHIM for the treatment of inhalational anthrax was studied in NZW rabbits and cynomolgus macaques. The animal efficacy studies were conducted under varying conditions and measured survival rates at Day 28 post-exposure.
The safety of ANTHIM was studied in healthy participants who were treated with one or more doses of 16 mg/kg IV ANTHIM in three clinical trials. Trial 1 was a single-dose placebo-controlled trial, Trial 2 was an open label repeat-dose trial, and Trial 3 was an open label, single-dose, drug interaction trial with ciprofloxacin.
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