Drug Trials Snapshots: VYEPTI
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 VYEPTI Package Insert for complete information.
VYEPTI (eptinezumab-jjmr)
vye ep' tee
Lundbeck
Approval date: February 21, 2020
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
VYEPTI is a drug used for the preventive treatment of migraine in adults.
A migraine is a type of headache that can be associated with nausea, vomiting, and/or sensitivity to light or sound.
How is this drug used?
VYEPTI is an injection given directly into the vein (intravenous infusion) by a healthcare provider every three months. It takes about 30 minutes to receive the VYEPTI infusion.
What are the benefits of this drug?
Over the three-month treatment period, patients treated with VYEPTI experienced fewer days of migraine headaches in comparison to patients who received the placebo treatment.
What are the benefits of this drug (results of trials used to assess efficacy)?
The tables below summarize efficacy results for the evaluated patients in Trials 1 and 2. The primary outcome was the change in monthly migraine days (MMD).
Table 1. Efficacy Endpoint Results in Trial 1
|
|
VYEPTI N=221 |
VYEPTI N=222 |
Placebo
N=222 |
|
Monthly Migraine Days (MMD) – Months 1-3 |
|
||
|
Change from baseline |
-3.9 |
-4.3 |
-3.2 |
|
Difference from placebo |
-0.7 |
-1.1 |
|
|
p-value |
0.018 |
<0.001 |
|
|
≥50% MMD responders – Months 1-3 |
|
||
|
% Responders |
49.8% |
56.3% |
37.4% |
|
Difference from placebo |
12.4% |
18.9% |
|
|
p-value |
0.009* |
<0.001 |
|
|
≥75% MMD responders – Months 1-3 |
|
||
|
% Responders |
22.2% |
29.7% |
16.2% |
|
Difference from placebo |
6.0% |
13.5% |
|
|
p-value |
NS** |
<0.001 |
|
* Nominal statistical significance
** NS = Not statistically significant
VYEPTI Prescribing Information
Table 2. Efficacy Endpoint Results in Trial 2
|
|
VYEPTI N=356 |
VYEPTI N=350 |
Placebo
N=366 |
|
Monthly Migraine Days (MMD) – Months 1-3 |
|
||
|
Change from baseline |
-7.7 |
-8.2 |
-5.6 |
|
Difference from placebo |
-2.0 |
-2.6 |
|
|
p-value |
<0.001 |
<0.001 |
|
|
≥50% MMD responders – Months 1-3 |
|
||
|
% Responders |
57.6% |
61.4% |
39.3% |
|
Difference from placebo |
18.2% |
22.1% |
|
|
p-value |
<0.001 |
<0.001 |
|
|
≥75% MMD responders – Months 1-3 |
|
||
|
% Responders |
26.7% |
33.1% |
15.0% |
|
Difference from placebo |
11.7% |
18.1% |
|
|
p-value |
<0.001 |
<0.001 |
|
VYEPTI Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: VYEPTI worked similarly in men and women.
- Race: The majority of patients were White. The number of patients in other races was limited; therefore, differences in how VYEPTI worked among races could not be determined.
- Age: VYEPTI worked similarly in all tested age groups. The number of patients older than 65 years was insufficient to determine if VYEPTI worked differently in this age group.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
The figures below summarize efficacy results by subgroups in Trials 1 and 2, respectively.
Figure 5. Forest Plot of Difference from Placebo in Monthly Migraine Days Change from Baseline Over Weeks 1-12 by Subgroup – VYEPTI 300 mg-Trial 1
Figure 6. Forest Plot of Difference from Placebo in Monthly Migraine Days Change from Baseline Over Weeks 1-12 by Subgroup – VYEPTI 100 mg-Trial 1
Figure 7. Forest Plot of Difference from Placebo in Monthly Migraine Days Change from Baseline Over Weeks 1-12 by Subgroup – VYEPTI 300 mg-Trial 2
Figure 8. Forest Plot of Difference from Placebo in Monthly Migraine Days Change from Baseline Over Weeks 1-12 by Subgroup – VYEPTI 100 mg-Trial 2
ALD403 300=VYEPTI 300 mg
FDA Statistical Review
What are the possible side effects?
VYEPTI may cause serious allergic reactions including swelling of face, tongue or throat, hives, trouble breathing, facial redness and rash.
The most common side effects of VYEPTI are stuffy nose and scratchy throat (nasopharyngitis) and allergic reactions.
What are the possible side effects (results of trials used to assess safety)?
The table below summarizes adverse reactions in adult patients with chronic or episodic migraine headaches in combined trials (safety population).
Table 4. Adverse Reactions Occurring with an Incidence of At Least 2% for VYEPTI At Least 2% Greater Than Placebo in Trials 1 and 2
|
Adverse Reactions |
VYEPTI 100 mg |
VYEPTI 300 mg |
Placebo |
|
Nasopharyngitis |
6 |
8 |
6 |
|
Hypersensitivity reactions* |
1 |
2 |
0 |
* Hypersensitivity reactions includes multiple related adverse event terms, such as hypersensitivity, pruritus, and flushing/hot flush that occurred on the day of dosing.
VYEPTI 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 majority of patients were White. The number of patients in other races was limited; therefore, differences in side effects among races could not be determined.
- Age: The occurrence of side effects was similar in patients younger and older than 40 years of age. The number of patients older than 65 years was insufficient to determine if the occurrence of side effects in this age group differ from the younger patients.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
The table below summarizes adverse events by subgroups in combined Trials 1 and 2.
Table 5. Rates of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) by Sex, Race and Age Subgroups Occurring in VYEPTI Treatment Arms (safety population)
|
|
Sex |
Race |
Age |
||||
|
Men |
Women |
White |
Black or African American |
Other* |
< 40 y |
≥ 40 y |
|
|
TEAEs |
79 |
528 |
530 |
59 |
18 |
297 |
310 |
|
SAEs |
1 |
13 |
12 |
2 |
0 |
5 |
9 |
*Other races = Asian, American Indian, Native Hawaiian, Multiple, Other, or Not Reported
Adapted from FDA Clinical Review
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved VYEPTI based primarily on evidence from two clinical trials (Trial 1/ NCT02559895 and Trial 2/ NCT02974153) of 1741 patients with chronic or episodic migraine headaches. Trials were conducted at 212 sites in United States, Georgia, Russia, Ukraine and European Union.
Figure 1 summarizes how many men and women were in the clinical trials.
Figure 1. Baseline Demographics by Sex
Adapted from FDA Review
Figure 2 summarizes the percentage of patients by race in the clinical trials.
Figure 2. Baseline Demographics by Race
*Other includes Asian, American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander Multiple and Other
Adapted from FDA Review
Figure 3 summarizes the percentage of patients by age in the clinical trials.
Figure 3. Baseline Demographics by Age
Adapted from FDA Review
Figure 4 summarizes the percentage of patients by ethnicity in the clinical trials.
Figure 4. Baseline Demographics by Ethnicity
Adapted from FDA Review
Who participated in the trials?
The table below summarizes demographics of the safety population.
Table 7. Baseline Demographics of the Safety Population
|
Demographic Parameters |
VYEPTI 100 mg |
VYEPTI 300 mg |
Placebo |
Overall |
|
Sex |
|
|
|
|
|
Men |
93 (16) |
61 (11) |
77 (13) |
231 (13) |
|
Women |
486 (84) |
513 (89) |
511 (87) |
1510 (87) |
|
Race |
|
|
|
|
|
White |
528 (91) |
509 (89) |
502 (85) |
1539 (88) |
|
Black or African American |
38 (7) |
50 (9) |
68 (12) |
156 (9) |
|
Asian |
2 (<1) |
2 (<1) |
3 (0.5) |
7 (<1) |
|
American Indian or Alaska Native |
1 (<1) |
3 (0.5) |
2 (<1) |
6 (<1) |
|
Native Hawaiian or Other Pacific Islander |
1 (<1) |
2 (<1) |
1 |
4 (<1) |
|
Multiple |
8 (1) |
7 (1) |
9 (1.5) |
24 (1) |
|
Other |
1(<1) |
1 (<1) |
3 (0.5) |
5 (<1) |
|
Age (years) |
|
|
|
|
|
Median (years) |
41 |
40 |
40 |
40 |
|
Min, max (years) |
18, 68 |
18, 71 |
18, 71 |
18, 71 |
|
Age Group |
|
|
|
|
|
≤ 35 years |
186 (32) |
203 (35) |
229 (39) |
618 (36) |
|
> 35 years and < 65 years |
390 (67) |
364 (63) |
350 (60) |
1104 (63) |
|
≥ 65 years |
3 (1) |
7 (1) |
9 (2) |
19 (1) |
|
Ethnicity |
|
|
|
|
|
Hispanic or Latino |
75 (13) |
58 (10) |
69 (11.7) |
202 (12) |
|
Not Hispanic or Latino |
504 (87) |
516 (90) |
519 (88) |
1539 (88) |
|
Region/Country |
|
|
|
|
|
United States |
382 (66) |
381 (66) |
417 (71) |
1180 (68) |
|
Republic of Georgia, Russia, |
147 (25) |
140 (24) |
120 (20) |
407(23) |
|
European Union |
50 (9) |
53 (9) |
51 (9) |
154 (9) |
Adapted from FDA Clinical Review
How were the trials designed?
The benefit and side effects of VYEPTI were evaluated in two clinical trials of adult patients 18 – 71 years of age with a history of migraine headaches. The trials had similar designs.
Trial 1 enrolled patients with a history of episodic migraine headaches and Trial 2 enrolled patients with chronic migraine headaches. Patients were assigned to receive one of two doses of VYEPTI or placebo injections every 3 months for a total of 12 months in Trial 1, and for a total of 6 months in Trial 2. Neither the patients nor the health care providers knew which treatment was being given until the trial was completed.
The benefit of VYEPTI in comparison to placebo was assessed based on the change in the number of migraine days per month during the first 3-month treatment period.
How were the trials designed?
The efficacy and safety of VYEPTI were evaluated in two similar, randomized, multicenter, placebo-controlled clinical trials.
Trial 1 enrolled patients with episodic migraine. VYEPTI or placebo was administered by intravenous infusion every 3 months for 12 months; however, the primary endpoint was measured at 12 weeks.
Trial 2 enrolled patients with chronic migraine. VYEPTI or placebo was administered by intravenous infusion every 3 months for 6 months; the primary endpoint was measured at 12 weeks.
The primary efficacy endpoint for both trials was the change from baseline in mean monthly migraine days over Months 1-3. Secondary endpoints included the percentages of patients with 50% or greater and 75% or greater reductions from baseline in monthly migraine days over Months 1-3.
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.
LINK TO DRUG PACKAGE INSERT