Drugs

Drug Trials Snapshots: AZEDRA

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 AZEDRA Package Insert for complete information.

AZEDRA (iobenguane I 131)
ah-‘zed-rƏ
Progenics Pharmaceuticals, Inc.
Approval date: July 30, 2018


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

AZEDRA is a radioactive drug for the treatment of patients 12 years and older who require systemic treatment (drugs that spread throughout the body to treat cancer cells) for tumors called pheochromocytomas or paragangliomas that have spread, or cannot be removed with surgery.

Pheochromocytoma is a rare tumor of the adrenal gland. When this type of tumor occurs outside the adrenal gland, it is called a paraganglioma. Both tumors increase the production of stress hormones (called epinephrine and norepinephrine), leading to high blood pressure and symptoms such as headaches, irritability, chest pain or anxiety.

How is this drug used?

AZEDRA is injected into a vein (intravenous) by a healthcare provider. The first injection is given to determine the treatment dose. After the first injection, two treatment doses are administered 90 days apart.

What are the benefits of this drug?

Out of 68 patients who received AZEDRA, 17 patients (25%) experienced at least a 50% reduction (including discontinuation) of all blood pressure medication for at least six months.

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

The table below summarizes efficacy results for the evaluated patients for Trial 2. The primary outcome was the proportion of patients with reduction of all antihypertensive medications by at least 50% maintained for at least 6 months.

Table 2. Efficacy Results in Patients with Pheochromocytoma or Paraganglioma in Trial 2

  At least the first therapeutic dose
N=68
Reduction of all antihypertensive medications by at least 50% maintained for at least 6 months, n (%)
Number of patients 17
Proportion of patients (95% CIa) 25% (16%, 37%)

a Calculated using the Agresti-Coull method.

Adapted from AZEDRA Prescribing Information

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

  • Sex: AZEDRA worked similarly in males and females.
  • Race: The majority of patients were White. The number of patients in other races was limited. Therefore, differences among race could not be determined.
  • Age: The number of patients older than 65 years was limited. Therefore, differences among age groups could not be determined.

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

The table below summarizes efficacy results by sex, race and age. Racial subgroup differences were investigated between White race and all other races combined since the majority of patients were White.

Table 3. Primary Endpoint in Subgroups

Subgroup Responders*/Total Patients, n (%)
Sex
Male 7/39 (18.0)
Female 10/29 (34.5)
Race
White 17/51 (33.3)
All Others 0/17 (0)**
Age Group
< 65 years 14/57 (24.6)
> 65 years 3/11 (27.3)

*Patients who had reduction (including discontinuation) of all antihypertensive medications by at least 50% maintained for at least 6 months.
**Although no response as defined by the primary endpoint was observed in African American or Asian patients, decrease in in blood pressure or blood pressure medication use which did not qualify for the primary endpoint and shrinkage of the tumor defined by imaging criteria were observed in the patients from the two groups. Given the small number of patients in these subgroups, the response rate defined by the primary endpoint is not expected to be predictive of clinical benefit by race.

FDA Review

What are the possible side effects?

AZEDRA may cause serious side effects including radiation exposure, decreased or abnormal bone marrow production of blood cells, increased risk of cancer, underactive thyroid, elevations in blood pressure, damage to the kidneys, lung inflammation, risk to a fetus, and infertility.

The most common side effects were low blood cells counts, and fatigue.

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

The table below summarizes adverse reactions in patients from both trials (safety population).

Table 4. Adverse Reactions Occurring in ≥10% of Patients Receiving Therapeutic Dose of AZEDRA in Trials 1 and 2

Adverse Reaction All Gradesa, (%) Gradesa 3 - 4, (%)
Hematologicb
Lymphopenia 96 78
Anemia 93 24
Thrombocytopenia 91 50
Neutropenia 84 59
Gastrointestinal
Nausea 78 16
Vomitingc 58 10
Dry mouth 48 2
Sialadenitisd 39 1
Diarrhea 25 3
Abdominal paine 23 6
Constipation 19 7
Oropharyngeal pain 14 0
Dyspepsia 10 0
General
Fatiguef 72 26
Pyrexia 14 2
Injection site pain 10 0
Hyperhidrosis 10 0
Alopecia 10 0
Infections
Upper respiratory tract infectiong 16 2
Urinary tract infection 11 1
Investigationsb
International normalized ratio increasedh 85 18
Increased blood alkaline phosphatase 53 5
Increased aspartate aminotransferase 50 2
Increased alanine aminotransferase 43 2
Metabolism and nutrition
Decreased appetite 30 5
Dehydration 16 4
Decreased weight 16 1
Musculoskeletal and connective tissue disorders
Back pain 17 2
Pain in extremity 15 0
Nervous system
DizzinessI 34 13
Headache 32 6
Dysgeusiaj 24 1
Respiratory, thoracic, and mediastinal disorders
Cough 18 0
Dyspnea 18 7
Vascular
Hypotension 24 4
Hypertensionk 20 11
Tachycardia 10 3

a NCI CTCAE version 3.0
b Based on laboratory data
c Includes vomiting and retching
d Includes sialoadenitis, salivary gland pain, and salivary gland enlargement
e Includes abdominal pain, abdominal pain upper, and abdominal pain lower.
f Incudes fatigue, asthenia.
g Includes upper respiratory tract infection, sinusitis, rhinorrhea, upper-airway cough syndrome, nasopharyngitis
h Only assessed in Study IB12B (N=68)
i Includes dizziness and dizziness postural
j Includes dysgeusia, hypogeusia and ageusia
k Includes blood pressure increased and hypertension.

AZEDRA Prescribing Information

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

  • Sex: The occurrence of side effects was similar in males and females.
  • Race: The majority of patients were White. The number of patients in other races was limited; therefore, differences in the occurrence of side effects among races could not be determined.
  • Age: The number of patients older than 65 years was limited. Therefore, differences in side effects among age groups 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 the most common adverse reaction, lymphopenia, by subgroup.

Table 5. Pooled Subgroup Analysis of Lymphopenia (safety population)

Demographic Characteristic AZEDRA
 n/N (%)
Sex
Male 49/51 (96.1)
Female 35/37 (94.6)
Race
White 63/66 (95.5)
Black or African American 16/17 (94.1)
Asian 5/5 (100.0)
Age Group
< 65years 70/74 (94.6)
> 65 years 14/14 (100.0)

Clinical Trial Data

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved AZEDRA based on evidence from two clinical trials (Trial 1 /NCT01413503 and Trial 2 /NCT00874614) of 88 patients with pheochromocytomas or paragangliomas that have spread and cannot be removed with surgery. The trials were conducted at 13 sites in the United States.

Both trials were used to evaluate safety of AZEDRA. The safety population is presented below. Only Trial 1 was used to evaluate the benefits of AZEDRA. Demographics of these patients are presented in Table 7, under the MORE INFO section.

Figure 1 summarizes the percentage of patients by sex in the combined clinical trials used to evaluate safety.

Figure 1. Baseline Demographics by Sex (safety population)

Pie chart summarizing how many males and females were in the clinical trial. In total, 51 (58%) males and 37 (42%) females participated in the clinical trials.

FDA Review

Figure 2 summarizes the percentage of patients by race in the combined clinical trials used to evaluate safety.

Figure 2. Baseline Demographics by Race (safety population)

Pie chart summarizing the percentage of patients by race enrolled in the clinical trials. In total, 66 (75%) White, 17 (19%) Black or African American, and 5 (6%) Asian patients participated in the clinical trials.

FDA Review

Table 1. Demographics of Clinical Trials by Race

Race Number of Patients Percentage of Patients
White 66 75%
Black or African American 17 19%
Asian 5 6%

FDA Review

Figure 3 summarizes the percentage of patients by age in the clinical trials used to evaluate safety.

Figure 3. Baseline Demographics by Age (safety population)

Pie chart summarizing how many individuals of certain age groups were enrolled in the clinical trial. In total, 74 patients (84%) were 65 years old and 14 patients (16%) were 65 years and older.

FDA Review

Who participated in the trials?

The table below summarizes demographics of all patients in the combined clinical trials.

Table 6. Demographic Characteristics for Trials 1 and 2 (safety population)

Demographic Characteristics AZEDRA (N=88)
n (%)
Sex
Male 51 (58.0%)
Female 37 (42.0%)
Race
White 66 (75.0%)
Black of African American 17 (19.3%)
Asian 5 (5.7%)
Mean Age (SD) 50.8 (13.7)
Age Group
< 65 years 74 (84.1%)
> 65 years 14 (15.9%)
Ethnicity
Not Hispanic or Latino 87 (98.9%)
Hispanic or Latino 1 (1.1%)
Region
United States 88 (100.0%)

FDA Review

The table below summarizes demographics of patients in Trial 2 used to assess efficacy.

Table 7. Demographic Characteristics of All Enrolled Patients in Trial 2 (efficacy population)

Demographic Characteristics AZEDRA (N=68)
>n (%)
Sex
Male 39 (57%)
Female 29 (43%)
Race
White 51 (75.0%)
Black of African American 14 (20.6%)
Asian 3 (4.4%)
Mean Age (SD) 50.9 (13.9)
Age Group
< 65 years 57 (83.8%)
> 65 11 (16.2%)
Ethnicity
Not Hispanic or Latino 67 (98.5%)
Hispanic or Latino 1 (1.5%)
Region
United States 68 (100.0%)

FDA Review

How were the trials designed?

The benefit and side effects of AZEDRA were evaluated in two clinical trials that enrolled patients with specific tumors called pheochromocytomas or paragangliomas that have spread and cannot be removed with surgery. The presence of all tumors was confirmed with an imaging scan.

Trial 1 enrolled adult patients who were 18 years and older. All patients received a starting dose of AZEDRA. Afterwards, patients were assigned to one of four strengths of AZEDRA that was given as a single injection within 7 – 28 days after the starting dose. Patients were evaluated for side effects.

Trial 2 enrolled patients who were 12 years and older. Patients received a starting dose of AZEDRA followed by 2 treatment doses 3 months apart. Patients were evaluated for side effects and benefit. The benefit of AZEDRA was assessed by the proportion of patients who achieved at least a 50% decrease in the use of blood pressure medications for 6 months.

How were the trials designed?

The safety and efficacy of AZEDRA were established in 2 open-label, single-arm trials. Patents with AZEDRA scan- positive, unresectable, locally advanced or metastatic pheochromocytomas and paragangliomas were evaluated.

Trial 1 was a dose-finding trial in adult patients. Following the dosimetric dose, patients received a single AZEDRA dose of 6, 7, 8, or 9 mCi/Kg within 7 -28 days. Patients were evaluated for safety.

Trial 2 evaluated patients 12 years of age and older. Following the dosimetric dose, patients were administered two therapeutic doses of AZEDRA (500mCi or 8mCi/kg for patients < 62.5 kg per dose) three months apart. The primary efficacy outcome was the proportion of patients with a reduction (including discontinuation) of all antihypertensive medications by at least 50% for at least 6 months.

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: 08/14/2018
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