Drug Trials Snapshots: ALIQOPA
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 ALIQOPA Prescribing Information for complete information.
ALIQOPA (copanlisib)
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Bayer HealthCare Pharmaceuticals Inc.
Approval date: September 14, 2017
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
ALIQOPA is used to treat adults with follicular lymphoma whose disease has come back after at least two previous treatments.
Follicular lymphoma is a slow-growing cancer of the lymph system, which is part of the body’s immune system.
ALIQOPA was approved under FDA’s accelerated approval program, which provides earlier patient access to a promising new drug while the company continues to conduct clinical trials to confirm that the drug works well.
How is this drug used?
ALIQOPA is given by a healthcare provider directly into the bloodstream through a needle in the vein. This is known as an intravenous, or IV infusion. It takes about one hour to receive an ALIQOPA infusion.
ALIQOPA is given once a week for the first three weeks of a four week treatment cycle (three weeks on and one week off).
What are the benefits of this drug?
In a clinical trial, 59 percent of 104 patients with follicular lymphoma had a complete or partial shrinkage of their tumors that lasted about 12 months.
There is an ongoing clinical trial to confirm the clinical benefit of ALIQOPA.
What are the benefits of this drug (results of trials used to assess efficacy)?
The table below summarizes efficacy results established on the basis of Overall Response Rate (ORR) assessed by an Independent Review Committee.
Table 2. Overall Response Rate (ORR) and Duration of Response (DOR) in Patients with Relapsed Follicular Lymphoma
| ALIQOPA N=104 | |
|---|---|
| ORR, n (%) | 61 (59%) |
| (95% CI) | (49, 68) |
| CR, n (%) | 15 (14%) |
| PR, n (%) | 46 (44%) |
| Median* DOR, months (range) | 12.2 (0+, 22.6) |
ORR = overall response rate; CI = confidence interval; CR = complete response;
PR = partial response; DOR = duration of response
*Kaplan-Meier estimate
ALIQOPA Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: ALIQOPA worked similarly in men and women.
- Race: Most of the patients were White. Differences in how well the drug worked among races could not be determined because of the small number of patients in other races.
- Age: ALIQOPA worked similarly in patients younger and older than 65 years of age.
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 demographic subgroups. Because of the small sample sizes, these exploratory analyses should be interpreted with caution.
Table 3. Subgroup Analyses of Objective Response Rate
| ALIQOPA n/N (%) | |
|---|---|
| Sex | |
| Men | 30/54 (55.6) |
| Women | 31/50 (62) |
| Age | |
| <65> | 39/63 (61.9) |
| ≥65 years | 22/41 (53.7) |
| Race | |
| White | 51/86 (53.9) |
| Asian | 7/13 (53.9) |
| Unknown | 3/5 (60) |
Adapted from FDA review
What are the possible side effects?
ALIQOPA may cause serious side effects including infections, high blood sugar levels (hyperglycemia), high blood pressure (hypertension), inflammation of the lungs (pneumonitis), decreased level of infection-fighting white blood cells (neutropenia) and skin rashes.
The most common side effects of ALIQOPA are high blood sugar levels, diarrhea, decreased general strength and energy, high blood pressure, low levels of certain white blood cells (leukopenia, neutropenia), nausea, lower respiratory tract infections, and low levels of blood platelets (thrombocytopenia).
What are the possible side effects (results of trials used to assess safety)?
The table below summarizes adverse reactions in patients with hematological malignancies including follicular lymphoma who were treated with at least one dose of ALIQOPA in the trial (safety population defined as all patients who were treated with ALIQOPA at recommended dose).
Table 4. Adverse Reactions Reported in ≥10% of Patients with Follicular Lymphoma and Other Hematological Malignancies Treated with ALIQOPA
| ADVERSE REACTIONS | ALIQOPA N = 168 |
||
|---|---|---|---|
| Any Grade n (%) |
Grade 3 n (%) |
Grade 4 n (%) |
|
| Metabolism and nutrition disorders | |||
| Hyperglycemia | 90 (54%) | 56 (33%) | 10 (6%) |
| Blood and lymphatic system disorders | |||
| Leukopenia | 61 (36%) | 20 (12%) | 26 (15%) |
| Neutropenia (including febrile neutropenia) | 53 (32%) | 16 (10%) | 26 (15%) |
| Thrombocytopenia | 37 (22%) | 12 (7%) | 2 (1%) |
| General disorders and administration site conditions | |||
| Decreased general strength and energy (includes fatigue and asthenia) | 61 (36%) | 6 (4%) | 0 |
| Gastrointestinal disorders | |||
| Diarrhea | 60 (36%) | 8 (5%) | 0 |
| Nausea | 43 (26%) | 1 (<> | 0 |
| Stomatitis (includes oropharyngeal erosion and ulcer, oral pain) | 24 (14%) | 3 (2%) | 0 |
| Vomiting | 21 (13%) | 0 | 0 |
| Vascular disorders | |||
| Hypertension (includes secondary hypertension) | 59 (35%) | 46 (27%) | 0 |
| Infections | |||
| Lower respiratory tract infections * | 35 (21%) | 20 (12%) | 3 (2%) |
| Skin and subcutaneous tissue disorders | |||
| Rash (includes exfoliative skin reactions) | 26 (15%) | 2 (1%) | 1 (<> |
*includes pneumonia, pneumonia bacterial, pneumonia pneumococcal, pneumonia fungal, pneumonia viral, pneumocystis jiroveci pneumonia, bronchopulmonary aspergillosis and lung infection)
ALIQOPA 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: Most of the patients were White. Differences in the occurrence of side effects among races could not be determined because of the small number of patients in other races.
- Age: The occurrence of side effects was similar in patients younger and older than 65 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
The table below summarizes some of the common adverse reactions by sex and age subgroup. Because of the small sample sizes, these exploratory analyses should be interpreted with caution.
Table 5. Subgroup Analyses of Common Adverse Reactions by Sex
| Adverse Reaction | Women N = 90 |
Men N = 78 |
Risk Difference | ||
|---|---|---|---|---|---|
| n | % | n | % | ||
| Hyperglycemia | 53 | 58.9 | 32 | 41.0 | 18 |
| Neutropenia | 27 | 30.0 | 15 | 19.2 | 11 |
| Hypertension | 35 | 38.9 | 23 | 29.5 | 9 |
Table 6. Subgroup Analyses of Common Adverse Events by Age Group
| Adverse Reaction | ≥ 65 Years of Age N = 80 |
< 65 Years of Age N = 88 |
Risk Difference | ||
|---|---|---|---|---|---|
| n | % | n | % | ||
| Hypertension | 37 | 46.3 | 21 | 23.9 | 22 |
| Hyperglycemia | 45 | 56.3 | 40 | 45.5 | 11 |
| Neutropenia | 23 | 28.6 | 19 | 21.6 | 7 |
Adapted from FDA Review
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved ALIQOPA based on evidence from one clinical trial (NCT 01660451) that was conducted in the United States, Canada, European Union, Korea, Singapore, Hong Kong, Israel, and Australia. Patients who participated in the trial had different types of the lymphatic cancers, but the majority of patients had follicular lymphoma.
Part of the trial population that was used to assess the side effects of ALIQOPA (called the safety population) is presented in the figures below. Some of these patients (total of 104 patients) represent the population that was used to establish the benefit of ALIQOPA (called the efficacy population). These patients are presented in Table 8 under MORE INFO section.
Figure 1 summarizes how many men and women were part of the trial that was used to evaluate side effects of ALIQOPA (safety population).
Figure 1. Baseline Demographics by Sex (safety population)
FDA review
Figure 2 and Table 1 below summarize patients by race in safety population.
Figure 2. Baseline Demographics by Race (safety population)
FDA review
Table 1. Baseline Demographics by Race
| Race | Number of Patients | Percentage |
|---|---|---|
| White | 140 | 83 |
| Black or African American | 0 | 0 |
| Asian | 15 | 9 |
| Not reported | 13 | 8 |
FDA review
Figure 3 summarizes patients by age in safety population.
Figure 3. Baseline Demographics by Age (safety population)
FDA review
Who participated in the trials?
The table below summarizes demographics of all patients in safety population.
Table 7. Baseline Demographics of Patients (safety population)
| Demographic Characteristic | ALIQOPA N=168 n (%) |
|---|---|
| Sex, n (%) Men Women |
78 (46.4) 90 (53.6) |
| Race, n (%) White Asian Not reported |
140 (83.3) 15 (8.9) 13 (7.7) |
| Age Median (years) Min, max (years) |
64 25, 82 |
| Age Group <65 years=""> ≥65 years |
88 (52.4) 80 (47.6) |
| Ethnicity Hispanic or Latino Not Hispanic or Latino Not reported |
10 (6) 140 (83.3) 18 (10.7) |
| Geographic Region US Other |
21 (12.5) 147 (87.5) |
Table 8 . Baseline Demographics of Patients (efficacy population)
| Demographic Characteristic | ALIQOPA N=104 n (%) |
|---|---|
| Sex, n (%) Men Women |
54 (51.9) 50 (48.1) |
| Race, n (%) White Asian Not reported |
86 (82.7) 13 (12.5) 5 (4.8) |
| Age Median (years) Min, max (years) |
62 25, 81 |
| Age Group <65 years=""> ≥65 years |
63 (60.6) 41 (39.4) |
| Ethnicity Hispanic or Latino Not Hispanic or Latino Not reported |
6 (5.8) 89 (85.6) 9 (8.7) |
| Geographic Region US Other |
11 (10.6) 93 (89.4) |
FDA review
How were the trials designed?
There was one trial that evaluated the benefit and side effects of ALIQOPA in patients with follicular lymphoma whose disease has come back after at least two previous treatments.
Patients received ALIQOPA on Days 1, 8, and 15 of a 28-day treatment cycle. Treatment continued until disease progression or unacceptable side effects.
The benefit of ALIQOPA was evaluated by measuring how many patients had complete or partial tumor shrinkage (response) and by how long that response lasted.
How were the trials designed?
The safety and efficacy of ALIQOPA were established in an open label, single-arm, multicenter trial in adult patients with relapsed or refractory follicular lymphoma.
Patients received ALIQOPA administered as a 1-hour intravenous infusion on Days 1, 8, and 15 of a 28-day treatment cycle on an intermittent schedule (three weeks on and one week off) until disease progression or unacceptable toxicity.
Tumor response was assessed according to the International Working Group response criteria for malignant lymphoma. Efficacy based on overall response rate (ORR) was assessed by an Independent Review Committee.
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.