Important Safety Information

Contraindication: Aimovig® is contraindicated in patients with serious hypersensitivity to erenumab-aooe or to any of the excipients. Reactions have included anaphylaxis and angioedema.

Hypersensitivity Reactions: Hypersensitivity reactions, including rash, angioedema, and anaphylaxis, have been reported with Aimovig® in post marketing experience. Most reactions were not serious and occurred within hours of administration, although some occurred more than one week after administration. If a serious or severe reaction occurs, discontinue Aimovig® and initiate appropriate therapy.

Constipation with Serious Complications: Constipation with serious complications has been reported following the use of Aimovig® in the postmarketing setting. There were cases that required hospitalization, including cases where surgery was necessary. The onset of constipation was reported after the first dose in a majority of these cases, but patients also reported later on in treatment. Aimovig® was discontinued in most reported cases. Constipation was one of the most common (up to 3%) adverse reactions reported in clinical studies.

Monitor patients treated with Aimovig® for severe constipation and manage as clinically appropriate. Concurrent use of medications associated with decreased gastrointestinal motility may increase the risk for more severe constipation and the potential for constipation-related complications.

Adverse Reactions: The most common adverse reactions in clinical studies (≥ 3% of Aimovig®-treated patients and more often than placebo) were injection site reactions and constipation.

Please see Aimovig® full Prescribing Information.


Indication

Aimovig® is indicated for the preventive treatment of migraine in adults.

It's time to give your patients...

MORE DAYS without migraine vs placebo

  • Patients experienced more migraine-free days starting at month 11
  • Up to half of Aimovig®-treated EM patients cut monthly migraine days by at least ≥ 50%1-3

MORE YEARS of data with Aimovig® than ever before

  • Established efficacy and safety out to 4.5 years in episodic migraine4
  • 3 out of 4 patients experienced at least ≥ 50% reduction in episodic migraine4

Aimovig®: evaluated in a broad range of patients1-3

Phase 3 Episodic Migraine Study Design

Aimovig® was evaluated for prevention of episodic migraine in adults aged 18-65 years with 4 to 14 monthly migraine days in a phase 3, randomized, multicenter, 24-week, placebo-controlled, double-blind study. The mean migraine frequency at baseline was ~ 8 monthly migraine days across treatment groups.1-3 

Following the 24-week double-blind treatment phase, patients were re-randomized to receive Aimovig® 70 mg
(n = 421) or 140 mg (n = 424) during the active treatment phase, with re-randomization stratified by treatment group assigned during the double-blind treatment phase.5

Following the 24-week double-blind treatment phase, patients were re-randomized to receive Aimovig® 70 mg (n = 421) or 140 mg (n = 424) during the active treatment phase, with re-randomization stratified by treatment group assigned during the double-blind treatment phase.5

Study design schematic for study in patients with episodic migraine Study design schematic for study in patients with episodic migraine

SC = subcutaneous; QM = once monthly.

*Baseline characteristics were similar between all treatment groups.

 

*SEE LONG-TERM EFFICACY AND SAFETY DATA BELOW*

*

SEE LONG-TERM EFFICACY
AND SAFETY DATA BELOW

*

 

Aimovig®: evaluated during a 4.5-year interim analysis4-6

Phase 2 Episodic Migraine Study Design

Aimovig® was evaluated in a phase 2, multicenter, randomized, placebo-controlled, double-blind, dose-finding study of subjects with episodic migraine. The mean migraine frequency at baseline was ~9 monthly migraine days across treatment groups (Placebo, n = 120; 70 mg, n = 88).

Following the 12-week, double-blind treatment phase, subjects were able to continue in a 5-year, open-label extension of Aimovig® (N = 383). The interim analysis for the open-label extension evaluated the long-term efficacy, safety, and tolerability of Aimovig® at 4.5 years of exposure. A protocol amendment increased the dosage to 140 mg in all subjects after a median of 2.0 years of exposure to 70 mg monthly in the OLTP. As post hoc analysis, efficacy was evaluated in these subjects based on last dose received. Analysis was conducted when all remaining patients completed 4.5 years of the 5-Year OLTP.4-6


Study design schematic for study in patients with episodic migraine Study design schematic for study in patients with episodic migraine

STUDY DESIGN: Aimovig® was evaluated in a phase 2, multicenter, randomized, placebo-controlled, double-blind, dose-finding study of subjects with episodic migraine. The mean migraine frequency at baseline was ~9 monthly migraine days across treatment groups (Placebo, n = 160; 70 mg, n = 107).2,5,6

OLTP = open-label treatment phase; SC = subcutaneous; QM = once monthly.

*Baseline characteristics were similar between all treatment groups.

Study included additional dose arms, which were not included in the FDA-approved labeling.

After a median 2 years of exposure to 70 mg monthly in the OLTP, patients continuing in the study increased dose to 140 mg monthly following a protocol amendment.

§Median exposure time presented.

12 weeks after last dose.

Aimovig®: evaluated in a broad range of patients2,8,9

Chronic Migraine Study Design

Aimovig® was evaluated for prevention of chronic migraine in patients with ≥ 15 headache days per month, including ≥ 8 migraine days per month, in a phase 2 randomized, multicenter, 12-week, placebo-controlled, double-blind study. The mean migraine frequency at baseline was ~18 monthly migraine days across treatment groups.2,8,9

Following the 12-week, DBTP, Aimovig® was evaluated for 1 year in an open-label treatment study. Patients originally received Aimovig® 70 mg monthly. A protocol amendment increased the dosage to 140 mg in subjects who had not yet completed the week 28 visit. Any subject who had a dose increase to 140 mg at or before week 28 had received 140 mg for at least 12 weeks. Patients were evaluated based on the last dose received.2,8,9


Study design schematic for study in patients with episodic migraine Study design schematic for study in patients with episodic migraine

DBTP = double-blind treatment phase; SC = subcutaneous; QM = once monthly.

*Baseline characteristics were similar between all treatment groups.

Phase 3 Episodic Migraine Study

Patients experienced more migraine-free days starting at month 11,2

Primary Outcome Measure

Change in Mean Monthly Migraine Days Between Baseline (~8 Monthly Migraine Days) and Months 4 to 61-3,*

Baseline = ~ 8 MMD

Line graph of primary endpoint results for study in patients with episodic migraine with a baseline of approximately 8 monthly migraine days Line graph of primary endpoint results for study in patients with episodic migraine with a baseline of approximately 8 monthly migraine days

*Least-squares means are presented. For Aimovig® 70 mg, the difference from placebo was -1.4 (95% CI: -1.9, -0.9). For Aimovig® 140 mg, the difference from placebo was -1.9 (95% CI: -2.3, -1.4).1,2

Earliest post-baseline prespecified assessment. Analysis is exploratory and has not been adjusted for multiple comparisons. No statistical conclusions can be drawn.1

After the 24-week DBTP, patients were re-randomized to receive Aimovig® 70 mg or 140 mg during the ATP, with re-randomization stratified by treatment group assigned during the DBTP.

Patients with ~ 8 MMD at baseline experienced up to 3.7 more migraine-free days over months 4 to 61
  • After 28 weeks in the ATP, change in MMD from baseline to 1 year: 4.2 fewer days with Aimovig® 70 mg (n = 369), and 4.6 fewer days with Aimovig® 140 mg (n = 368).1,3,‡

ATP = active treatment phase; DBTP = double-blind treatment phase;
MMD = monthly migraine days.

Phase 2 Episodic Migraine Study

Aimovig demonstrated sustained efficacy with results out to 4.5 years4,§

*LONG-TERM EFFICACY DATA*

Outcome Measure

Change From Baseline in Mean Monthly Migraine Days (~ 9 MMD) at Month 3 and Year 4.5 4,|

Mean Change from baseline Mean Change from baseline

The primary outcome measure was the change in mean MMD at month 3. At year 3, after a median 2.0 years of exposure to 70 mg monthly in the OLTP, patients increased dose to 140 mg monthly. Consider open-label extension study limitation when interpreting results. The open-label extension study was not blinded, not controlled, and included inherent self-selection bias for remaining in the trial. Overall, a total of 162 patients (42.3%), discontinued during the study, of which 19 patients (5.0%) discontinued due to adverse events.4

  OLTP = open-label treatment phase.

§In a preplanned interim analysis of a 5-year open-label treatment phase (OLTP).

Study included additional dose arms, which were not included in FDA-approved-labeling.

With Aimovig®, patients can get more days back per month2,8,9,*

Outcome Measure

Change in Mean Monthly Migraine Days Between Baseline (~ 18 Monthly Migraine Days) at Month 3 and at Month 162,8,9

Line graph of primary endpoint results for study in patients with chronic migraine with a baseline of approximately 18  monthly migraine days Line graph of primary endpoint results for study in patients with chronic migraine with a baseline of approximately 18  monthly migraine days

For the open-label extension, consider treatment phase study limitations when interpreting results. The open-label treatment phase was not blinded, and included inherent self-selection bias. Overall, 22.8% (n = 139) patients discontinued Aimovig® during the study, of which 16 patients (2.6%) discontinued due to AE.

Patients who completed the 1-year OLE had received the same OLE dose (70 mg QM vs 140 mg QM) for at least 6 months at week 52. Since subjects who switched from 70 mg QM to 140 mg QM should reach steady state ~ 3 months after the dose switch, week 52 should reflect the efficacy at 140 mg QM in patients who increased the Aimovig® dose and completed the OLE. As a post-hoc analysis, efficacy was evaluated in these subjects based on the last dose.10

AE = adverse events; CI = confidence interval; OLE = open-label extension; QM = once monthly.

*vs placebo in the DBTP; vs baseline in the OLE.

Least-squares means are presented. Statistically significant reductions from baseline in mean monthly migraine days at month 3 for Aimovig® 70 mg and 140 mg vs placebo (P < 0.001). For both Aimovig® 70 mg and Aimovig® 140 mg, the difference from placebo was ‒2.5 (95% CI: ‒3.5, ‒1.4).2,8

Phase 3 Episodic Migraine Study

Up to half of Aimovig®-treated patients cut migraine days by at least 50%1-3

Outcome Measure:
Proportion of patients achieving at least a 50% reduction in mean monthly migraine days from baseline during months 4 to 6 and at year 11,2
Bar graph of secondary endpoint results for study in patients with episodic migraine with a baseline of approximately 8 monthly migraine days Bar graph of secondary endpoint results for study in patients with episodic migraine with a baseline of approximately 8 monthly migraine days

In an exploratory analysis

~ 1 in 5 Aimovig®-treated patients cut migraine days by at least 75%11,‡

Exploratory Analysis Exploratory Analysis

Analysis is exploratory and has not been adjusted for multiple comparisons. No conclusions of statistical or clinical significance can be drawn.

*Odds of achieving a ≥ 50% reduction were significantly higher (2.1x, 95% CI: 1.5, 3.0) for Aimovig® 70 mg group than for the placebo group (P < 0.001).1,2

Odds of achieving a ≥ 50% reduction were significantly higher (2.8x, 95% CI: 2.0, 3.9) for Aimovig® 140 mg group than for the placebo group (P < 0.001).1,2

75% reduction from baseline in mean monthly migraine days was observed during months 4 to 6.1,2

Phase 2 Episodic Migraine Study

At 4.5 years, patients experienced at least ≥ 50% fewer migraine days4

  • 46.5% of Aimovig® 70 mg patients achieved a ≥ 50% response at the 3-month, double-blind treatment phase portion of this study vs 30% for placebo5

Roughly half of patients cut migraine days by at least ≥ 75%4

75% more response 75% more response
  • 20.7% of Aimovig® 70 mg patients achieved a ≥ 75% response at the 3-month, double-blind treatment phase portion of this study vs 13.3% for placebo12

Consider open-label extension study limitations when interpreting results. The open-label extension study was not blinded, not controlled, and included inherent self-selection bias for remaining in the trial. A total of 162 patients (42.3%) discontinued during the study, of which 18 patients (4.7%) discontinued due to adverse events.4

MMD = monthly migraine days.

Aimovig® reduced migraine frequency by at least 50% for many patients in chronic migraine2,8

Secondary Outcome Measure:

Proportion of patients achieving at least a 50% reduction in MMD from baseline at month 32,8

50% reduction 50% reduction

~ 40% of patients achieved at least a 50% reduction in monthly migraine days with Aimovig®2,8

MMD = monthly migraine days.

*Odds of achieving a ≥ 50% reduction were significantly higher (2.2x, 95% CI: 1.5, 3.3) for the Aimovig® 70 mg group than for the placebo group (P < 0.001).

Odds of achieving a ≥ 50% reduction were significantly higher (2.3x, 95% CI: 1.6, 3.5) for the Aimovig® 140 mg group than for the placebo group (P < 0.001).

Aimovig®: established safety profile in a broad range of patients2

Safety Across Pooled Pivotal Studies of Episodic and Chronic Migraine—at Month 32

Table of most common adverse reactions occurring with Aimovig® (erenumab-aooe) Table of most common adverse reactions occurring with Aimovig® (erenumab-aooe)
  • 90% of patients with episodic migraine completed the 6-month DBTP; < 2% of patients receiving Aimovig discontinued due to adverse events2
  • 95% of patients completed the 3-month chronic migraine study; < 2% of patients receiving Aimovig discontinued due to adverse events2

Phase 3 Episodic Migraine ATP Safety Data and Completion Rates—1 Year

  • Treatment-emergent AEs were reported in 57.2% of patients in the 70 mg group (6.2% ≥ Grade 3) and 55% in the 140 mg group (4.7% ≥ Grade 3)13
  • Serious AEs were observed in 3.3% of patients in both the 70 mg group and the 140 mg group13
  • Fatal AEs were reported in 1 patient (0.2%) treated in the 140 mg group13
  • Most frequent AEs were viral URI, URI, UTI, influenza, sinusitis, and arthralgia13
  • 90.4% of patients with episodic migraine completed the STRIVE ATP (6 months to 1 year); 2% of patients discontinued due to AEs3,13,‡

*Injection site reactions include multiple preferred terms, such as injection site pain and injection site erythema.2

The rate of injection site reactions reported is with the prefilled syringe.2

The most frequently reported reasons (≥ 1.0% of total subjects) for discontinuation of Aimovig® were subject request (4.9%), adverse event (2.0%), and lost to follow-up (1.4%)3,13

Safety established over 4.5 years in episodic migraine4

The safety profile observed in the OLE was consistent with what was observed in the DBTP

Phase 2 Episodic Migraine OLTP Safety Data—Through 4.5 Years4

Safety-Study Safety-Study
  • Most frequent AEs in OLTP were nasopharyngitis, upper respiratory tract infection, influenza, sinusitis, back pain, and urinary tract infection, and arthralgia4,‖
  • 57.7% of patients completed the 4.5-year interim analysis of a 5-year phase 2 EM open-label extension study; 4.7% of patients (n = 18) discontinued due to adverse events4,¶

AE = adverse event; ATP = active treatment phase; ECG = electrocardiogram; EM = episodic migraine; n= number of patients reporting at least 1 occurrence of event; DBTP = double-blind treatment phase; OLTP = open-label treatment phase; QM = once monthly; URI = upper respiratory tract infection; UTI = urinary tract infection.

§Fatality, previously reported, due to arteriosclerosis occurred in patient with history of hypertension and left anterior hemiblock (ECG), who on autopsy showed evidence of severe coronary artery disease and presence of cardiac stimulants (liver tissue) -considered not related to investigational product by investigator.4

Events with ≥ 4.2 patients per 100 patient-years in the erenumab 70 mg/140 mg group.

The most frequently reported reasons ( > 1.0% of total subjects) for discontinuation of Aimovig® were subject request (21.9%), adverse event (5.0%), lost to follow-up (3.7%), lack of efficacy (3.1%), Other (2.3%), Non-compliance (1.8%), pregnancy (1.8%), and requirement for alternative therapy (1.0%).4

Phase 2 Chronic Migraine OLE Safety Data and Completion Rates—1 Year

  • The exposure-adjusted incidence rate for all AEs was 132 in the 70 mg group (6.6 with > Grade 3) and 148.5 in the 140 mg group (3.7 with > Grade 3)9,14,‡
  • The exposure-adjusted incidence rate for serious AEs was 3.3 in the 70 mg group and 4.7 in the 140 mg group9,14
  • Most frequent AEs were viral URI, URI, sinusitis, arthralgia, migraine, back pain, injection site pain, fatigue, nausea9,14
  • 77.2% of patients completed the 1-year CM open-label extension study; 2.6% of patients discontinued due to adverse events9,14,‡

AE = adverse event; CM = chronic migraine; DBTP = double-blind treatment phase; OLE = open-label extension; URI = upper respiratiory tract infection; UTI = urinary tract infection.

*Injection site reactions include multiple preferred terms, such as injection site pain and injection site erythema.

The rate of injection site reactions reported is with the prefilled syringe.

The most frequently reported reasons ( ≥ 1.0% of total subjects) for discontinuation of Aimovig® were subject request (10.5%), lack of efficacy (6.4%), adverse event (2.6%), and lost to follow-up (1.5%).9,14

Indication

Aimovig® is indicated for the preventive treatment of migraine in adults.

Important Safety Information

Contraindication: Aimovig® is contraindicated in patients with serious hypersensitivity to erenumab-aooe or to any of the excipients. Reactions have included anaphylaxis and angioedema.

Hypersensitivity Reactions: Hypersensitivity reactions, including rash, angioedema, and anaphylaxis, have been reported with Aimovig® in post marketing experience. Most reactions were not serious and occurred within hours of administration, although some occurred more than one week after administration. If a serious or severe reaction occurs, discontinue Aimovig® and initiate appropriate therapy.

Constipation with Serious Complications: Constipation with serious complications has been reported following the use of Aimovig® in the postmarketing setting. There were cases that required hospitalization, including cases where surgery was necessary. The onset of constipation was reported after the first dose in a majority of these cases, but patients also reported later on in treatment. Aimovig® was discontinued in most reported cases. Constipation was one of the most common (up to 3%) adverse reactions reported in clinical studies.

Monitor patients treated with Aimovig® for severe constipation and manage as clinically appropriate. Concurrent use of medications associated with decreased gastrointestinal motility may increase the risk for more severe constipation and the potential for constipation-related complications.

Adverse Reactions: The most common adverse reactions in clinical studies (≥ 3% of Aimovig®-treated patients and more often than placebo) were injection site reactions and constipation.

Please see Aimovig® full Prescribing Information.

References: 1. Goadsby PJ, Reuter U, Hallström Y, et al. A controlled trial of erenumab for episodic migraine. N Engl J Med. 2017;377(22):2123-2132. 2. Aimovig® (erenumab-aooe) prescribing information, Amgen. 3. Goadsby PJ, Reuter U, Hallström Y, et al. Sustained efficacy over 1 year of treatment with erenumab: results from the extension phase of the STRIVE study in episodic migraine. Poster presented at: 12th European Headache Federation Congress (EHF); September 28–30, 2018; Florence, Italy. 4. Ashina M, Goadsby PJ, Reuter U, et al. Sustained efficacy and long-term safety of erenumab in patients with episodic migraine: 4+-year results of a 5-year, open-label treatment period. Oral presentation at: American Headache Society, 61st Annual Scientific Meeting; July 11-14, 2019; Philadelphia, PA. 5. Sun H, Dodick DW, Silberstein S, et al. Appendix for: Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomized, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 2016;15(4):382-390. 6. Ashina M, Tepper SJ, Brandes JL, et al. Efficacy and safety of erenumab (AMG 334) in chronic migraine patients with prior preventive treatment failure: a subgroup analysis of a randomized, double-blind, placebo-controlled study. Cephalalgia. 2018;38(10):1611-1621. 7. Ashina M, Goadsby PJ, Reuter U, et al. Long-term safety and tolerability of erenumab: three-plus year results from an ongoing open-label extension study in episodic migraine. Oral presentation at: American Headache Society, 60th Annual Scientific Meeting; June 28–July 1, 2018; San Francisco, CA. 8. Tepper S, Ashina M, Reuter U, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017;16(6):425-434. 9. Tepper SJ, Ashina M, Reuter U, et al. Assessment of the long-term safety and efficacy of erenumab during open-label treatment in subjects with chronic migraine. Poster presented at: American Headache Society, 60th Annual Scientific Meeting; June 28–July 1, 2018; San Francisco, CA. 10. Data on file, Amgen Inc. AMG 334 Clinical Study Report: 20130255 Final Analysis. February 16, 2018. 11. Brossner G, Reuter U, Bonner J, et al. Achievement of ≥ 75% and 100% response in patients treated with erenumab: 24-week results from the STRIVE study. Poster presented at: 18th Congress of the International Headache Society; September 7-10, 2017; Vancouver, Canada. 12. Data on file, Amgen Inc. AMG 334 Abbreviated Clinical Study Report: 20120178. January 28, 2016. 13. Data on file, Amgen Inc. AMG 334 Abbreviated Clinical Study Report: 20120296. July 16, 2018. 14. Data on file, Amgen Inc. AMG 334 Clinical Study Report: 20130255 Final Analysis. February 16, 2018.