Drug Trials Snapshots: BLENREP
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 BLENREP Prescribing Information for complete information.
BLENREP (belantamab mafodotin-blmf)
blen-rep
GlaxoSmithKline
Approval date: August 5, 2020
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
BLENREP is a drug used to treat a form of blood cancer called multiple myeloma. It is to be used in patients with whose cancer came back after, or did not respond to, at least four previous treatments.
How is this drug used?
BLENREP is given directly into the vein (an I.V. infusion) by a heathcare professional every three weeks. It takes about 30 minutes to receive the BLENREP infusion.
What are the benefits of this drug?
In the trial, 30 of 97 patients (31%) treated with BLENREP experienced an improvement in their disease. For seventy-three percent of responders that improvement lasted at least 6 months.
BLENREP 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.
What are the benefits of this drug (results of trials used to assess efficacy)?
The efficacy of BLENREP was evaluated by ORR, as assessed by an Independent Review Committee (IRC) based on the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma.
Table 1. Efficacy Results
|
BLENREP |
Overall response rate (ORR), n (%) |
30 (31%) |
Stringent complete response (sCR), n (%) |
2 (2%) |
Complete response (CR), n (%) |
1 (1%) |
Very good partial response (VGPR), n (%) |
15 (15%) |
Partial response (PR), n (%) |
12 (12%) |
Median duration of response in monthsa (range) |
NR [NR to NR] |
BLENREP Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: BLENREP was similarly effective in men and women.
- Race: The majority of patients were White. Differences in effectiveness among races could not be determined because of the small number of patients in other races.
- Age: Differences in the effectiveness of BLENREP among patients below and above 65 years of age could not be determined because of the small numbers of patients aged 65 and above.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
The table below summarizes subgroup analysis of ORR.
Table 2. Subgroup Analysis of ORR
Subgroup |
n (%); [97.5% CI] |
All Patients (N=97) |
30 (30.9); [20.8, 42.6] |
Sex |
|
Men (N = 51) |
14 (27.5); [14.6, 43.7] |
Women (N = 46) |
16 (34.8); [19.8, 52.3] |
Race |
|
White (N = 76) |
24 (31.6); [20.1, 44.9] |
Black or African American (N = 16) |
6 (37.5); [13.1, 67.7] |
Othera (N=5) |
0 (0.0); [0.0, 58.4] |
Age |
|
18-64 years (N = 45) |
12 (26.7); [13.3, 44.1] |
65-74 years (N = 39) |
17 (43.6); [25.9, 62.5] |
≥ 75 years (N = 13) |
1 (7.7); [0.1, 40.1] |
Adapted from FDA Review
What are the possible side effects?
BLENREP may cause serious changes to the surface of the eye (cornea) that can lead to worsening vision and vision loss. Because of the eye problems BLENREP is available only through a drug safety program called the BLENREP Risk Evaluation and Mitigation Strategy (REMS). Other serious side effects include low platelet counts, infusion related reactions, and harm to an unborn baby. The most common side effects of BLENREP are corneal changes, decreased vision or blurred vision , nausea, low blood cell counts, fever, infusion-related reactions, fatigue, and changes in kidney or liver function blood tests.
What are the possible side effects (results of trials used to assess safety)?
The table below summarizes the adverse reactions.
Table 3. Adverse Reactions (≥10%) in Patients Who Received BLENREP
Adverse Reactions |
BLENREP |
|
All Grades |
Grade 3-4 |
|
Eye disorders |
|
|
Keratopathya |
71 |
44 |
Decreased visual acuityb |
53 |
28 |
Blurred visionc |
22 |
4 |
Dry eyesd |
14 |
1 |
Gastrointestinal disorders |
|
|
Nausea |
24 |
0 |
Constipation |
13 |
0 |
Diarrhea |
13 |
1 |
General disorders and administration site conditions |
|
|
Pyrexia |
22 |
3 |
Fatiguee |
20 |
2 |
Procedural complications |
|
|
Infusion-related reactionsf |
21 |
3 |
Musculoskeletal and connective tissue disorders |
|
|
Arthralgia |
12 |
0 |
Back pain |
11 |
2 |
Metabolic and nutritional disorders |
|
|
Decreased appetite |
12 |
0 |
Infections and infestations |
|
|
Upper respiratory tract infectiong |
11 |
0 |
a Keratopathy was based on slit lamp eye examination, characterized as corneal epithelium changes with or without symptoms.
b Visual acuity changes were determined upon eye examination.
c Blurred vision included diplopia, vision blurred, visual acuity reduced, and visual impairment.
d Dry eyes included dry eye, ocular discomfort, and eye pruritus.
e Fatigue included fatigue and asthenia.
f Infusion-related reactions included infusion-related reaction, pyrexia, chills, diarrhea, nausea, asthenia, hypertension, lethargy, tachycardia.
g Upper respiratory tract infection included upper respiratory tract infection, nasopharyngitis, rhinovirus infections, and sinusitis.
BLENREP 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 between White and Black or African American patients was similar. Differences in side effects among other races could not be determined because of the small number of patients in those races.
- Age: The occurence of overall side effects was similar in patients below and above 65 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
The tables below summarize adverse reactions (AR) by subgroups in pooled safety population (N=103) of all patients who received the recommended BLENREP dose during the drug development program.
Table 4. Summary of Adverse Reactions by Sex
AR Category |
Men |
Women |
Any AR |
51 (98) |
50 (98) |
Keratopathy* |
32 (62%) |
36 (71%) |
Any Grade 3 or 4 AR |
42 (81) |
40 (78) |
Serious AR |
25 (48) |
17 (33) |
Table 5. Summary of Adverse Reactions by Race
|
White |
Black or African American |
Any AR |
77 (97) |
19 (100) |
Keratopathy* |
53 (67) |
12 (63) |
Any Grade 3 or 4 AR |
65 (82) |
14 (74) |
Serious AR |
36 (46) |
5 (26) |
Table 6. Summary of Adverse Reactions by Age
AR Category |
<65 years |
≥65 to 75 years |
≥75 years |
Any AR |
47 (98) |
40 (100) |
14 (93) |
Keratopathy* |
30 (63) |
31 (78) |
7 (47) |
Any Grade 3 or 4 AR |
39 (81) |
34 (85) |
9 (60) |
Serious AR |
19 (40) |
18 (45) |
5 (33) |
Clinical Trial Data
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved BLENREP based primarily on evidence from a clinical trial (NCT03525678) which enrolled patients with multiple myeloma whose disease came back after, or did not respond to, previous treatments. The trial was conducted at 59 sites in US, Canada, Europe and Australia.
Presented below is the population that provided data for evaluation of the BLENREP benefit (efficacy population).
Figure 1 summarizes how many men and women were in the clinical trial.
Figure 1. Baseline Demographics by Sex (efficacy population)
FDA Review
Figure 2 summarizes the percentage of patients by race in the clinical trial.
Figure 2. Baseline Demographics by Race (efficacy population)
FDA Review
Figure 3 summarizes the percentage of patients by age group in the clinical trial.
Figure 3. Baseline Demographics by Age (efficacy population)
FDA Review
Figure 4 summarizes the percentage of patients by ethnicity in the clinical trial.
Figure 4. Baseline Demographics by Ethnicity (efficacy population)
FDA Review
The tables below summarize efficacy population from the trial.
Table 7. Demographics of Patients in the Clinical Trial (efficacy population)
Demographic Parameter |
BLENREP |
Sex, n (%) |
|
Men |
51 (53) |
Women |
46 (47) |
Race, n (%) |
|
White |
76 (78) |
Black or African American |
16 (16) |
Asian |
2 (2) |
Multiple |
1 (1) |
Not Reported |
2 (2) |
Age (years) |
|
Mean±SD |
64.1±10.01 |
Median (range) |
65.0 (39 to 85) |
Age Group , n (%) |
|
18 to <65 years |
45 (46) |
65 to <75 years |
39 (40) |
³75 years |
13 (13) |
Ethnicity, n (%) |
|
Hispanic or Latino |
4 (4) |
Not Hispanic or Latino |
91 (94) |
Not Reported |
2 (2) |
Region, n(%) |
|
USA |
59 (61) |
Canada |
2 (2) |
Europe |
34 (35) |
Australia |
2 (2) |
Adapted from FDA Review
How were the trials designed?
There was one trial that provided data for BLENREP’s approval.
The trial enrolled patients with multiple myeloma whose disease came back after, or did not respond to, previous treatments. All patients in the trial received BLENREP every three weeks until the disease progressed or the side effects became too toxic.
The benefit of BLENREP was measured by the proportion of patients that achieved improvement (overall response rate or ORR).
How were the trials designed?
The efficacy and safety of BLENREP were evaluated in a multicenter, open-label trial of patients with relapsed refractory multiple myeloma who had previously received 3 or more anti-myeloma treatment regimens, and whose disease no longer responded to an immunomodulatory agent and a proteasome inhibitor. Treatment was administered as an intravenous infusion once every 3 weeks until disease progression or unacceptable toxicity.
The primary endpoint was ORR, defined as the proportion of patients with a PR or better, as assessed by an IRC based on the IMWG Uniform Response Criteria for Multiple Myeloma.
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.