Efficacy and safety of erenumab (AMG334) in episodic migraine patients with prior preventive treatment failure: A subgroup analysis of a randomized, double-blind, placebo-controlled study

Cephalalgia ◽  
2019 ◽  
Vol 39 (7) ◽  
pp. 817-826 ◽  
Author(s):  
Peter J Goadsby ◽  
Koen Paemeleire ◽  
Gregor Broessner ◽  
Jan Brandes ◽  
Jan Klatt ◽  
...  
Keyword(s):  
Placebo Response ◽  
Preventive Treatment ◽  
Episodic Migraine ◽  
Prior Treatment ◽  
Controlled Study ◽  
Study Phase ◽  
Acute Migraine ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Specific Medication

Background Erenumab was effective and well tolerated in a pivotal clinical trial of episodic migraine that included subjects both naïve to, and those who had failed, previous preventives. Here we evaluated the efficacy and safety of erenumab (70 mg or 140 mg) versus placebo in the subgroup of patients who had previously failed preventive treatment(s): ≥1 or ≥2 prior failed migraine preventive categories, and in patients who had never failed. Methods Prespecified subgroup analyses evaluated change from baseline to months 4–6 (the primary endpoint of the blinded study phase) in monthly migraine days, achievement of ≥50% and ≥75% reduction in monthly migraine days, and change from baseline in acute migraine-specific medication days. Adverse events were also evaluated. Results Treatment with both doses of erenumab resulted in greater reductions in monthly migraine days at months 4–6 (treatment difference versus placebo [95% CI], never failed subgroup: −0.9 [−1.5, −0.3] for 70 mg and −1.3 [−1.9, −0.7] for 140 mg; ≥1 prior failed medication categories subgroup: −2.0 [−2.8, −1.2] for 70 mg and −2.5 [−3.4, −1.7] for 140 mg; ≥2 prior failed medication categories subgroup: −1.3 [−2.6, 0.0] for 70 mg and −2.7 [−4.0, −1.4] for 140 mg). Similar results were observed in the monthly acute migraine-specific medication days endpoint, and in the achievement of ≥50% and ≥75% reduction in monthly migraine days. For the ≥50% reduction in monthly migraine day endpoint, placebo response in the no prior treatment failed group was 32.6%, in the ≥1 failed treatment 17.5%, and in the ≥2 failed treatments 11.1%. Conclusion Erenumab showed consistent efficacy in episodic migraine patients who had failed prior preventive treatments and was well tolerated across subgroups. The data suggest prior patients with prior treatment failures have lower placebo response rates.

Efficacy and safety of erenumab (AMG334) in chronic migraine patients with prior preventive treatment failure: A subgroup analysis of a randomized, double-blind, placebo-controlled study

Cephalalgia ◽  
2018 ◽  
Vol 38 (10) ◽  
pp. 1611-1621 ◽  
Author(s):  
Messoud Ashina ◽  
Stewart Tepper ◽  
Jan Lewis Brandes ◽  
Uwe Reuter ◽  
Guy Boudreau ◽  
...  
Keyword(s):  
Chronic Migraine ◽  
Preventive Treatment ◽  
Controlled Study ◽  
Acute Migraine ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Safety Issues ◽  
Subgroup Analyses ◽  
Specific Medication

Background Erenumab was effective and well tolerated in a pivotal clinical trial of chronic migraine. Here, we evaluated efficacy and safety of monthly erenumab (70 mg or 140 mg) versus placebo in the subgroup of patients who had previously failed preventive treatment(s) (≥ 1, ≥ 2 prior failed medication categories) and in patients who had never failed. Methods Subgroup analyses evaluated change from baseline in monthly migraine days; achievement of ≥ 50% and ≥ 75% reduction in monthly migraine days; and change in monthly acute migraine-specific medication days. Adverse events were evaluated for each subgroup. Results Treatment with both doses of erenumab resulted in greater reductions in monthly migraine days (primary endpoint) at Month 3 (treatment difference [95% CI], never failed subgroup: −2.2 [−4.1, −0.3] for 70 mg and −0.5 [−2.4, 1.5] for 140 mg; ≥ 1 prior failed medication categories subgroup: −2.5 [−3.8, −1.2], for 70 mg and −3.3 [−4.6, −2.1] for 140 mg; ≥ 2 prior failed medication categories subgroup: −2.7 [−4.2, −1.2], for 70 mg and −4.3 [−5.8, −2.8] for 140 mg). Similar results were observed in the monthly acute migraine-specific medication days endpoint, and in the achievement of ≥ 50% and ≥ 75% reduction in monthly migraine days. There were no new or unexpected safety issues. Conclusion Erenumab showed consistent efficacy in chronic migraine patients who had failed prior preventive treatments and was well tolerated across subgroups.

scholarly journals Efficacy and safety of erenumab in Japanese migraine patients with prior preventive treatment failure or concomitant preventive treatment: subgroup analyses of a phase 3, randomized trial

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Koichi Hirata ◽  
Fumihiko Sakai ◽  
Takao Takeshima ◽  
Noboru Imai ◽  
Yasuhiko Matsumori ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Preventive Treatment ◽  
Controlled Study ◽  
Acute Migraine ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Subgroup Analyses ◽  
Specific Medication

Abstract Background These subgroup analyses of a Phase 3, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of erenumab 70 mg in Japanese migraine patients with/without prior preventive treatment failure(s) (“failed-yes” and “failed-no” subgroups) and with/without concomitant preventive treatment (“concomitant preventive-yes” and “concomitant preventive-no” subgroups). Methods Overall, 261 patients were randomized; 130 and 131 patients to erenumab 70 mg and placebo, respectively. Subgroup analyses evaluated the change from baseline to Months 4–6 in mean monthly migraine days (MMD) (primary endpoint), achievement of a ≥50% reduction in mean MMD, and change from baseline in mean monthly acute migraine-specific medication (MSM) treatment days. Treatment-emergent adverse events were also evaluated. Results Of the 261 patients randomized, 117 (44.8%) and 92 (35.3%) patients were in the failed-yes and concomitant preventive-yes subgroups, respectively. Erenumab 70 mg demonstrated consistent efficacy across all subgroups, with greater reductions from baseline in mean MMD versus placebo at Months 4–6 (treatment difference versus placebo [95% CI], failed-yes: − 1.9 [− 3.3, − 0.4]; failed-no: − 1.4 [− 2.6, − 0.3]; concomitant preventive-yes: − 1.7 [− 3.3, 0.0]; concomitant preventive-no: − 1.6 [− 2.6, − 0.5]). Similar results were seen for achievement of ≥50% reduction in mean MMD and change from baseline in mean monthly acute MSM treatment days. The safety profile of erenumab 70 mg was similar across subgroups, and similar to placebo in each subgroup. Conclusion Erenumab was associated with clinically relevant improvements in all efficacy endpoints and was well tolerated across all subgroups of Japanese migraine patients with/without prior preventive treatment failure(s) and with/without concomitant preventive treatment. Trial registration Clinicaltrials.gov. NCT03812224. Registered January 23, 2019.

scholarly journals Randomised, controlled trial of erenumab for the prevention of episodic migraine in patients from Asia, the Middle East, and Latin America: The EMPOwER study

Cephalalgia ◽  
2021 ◽  
pp. 033310242110241
Author(s):  
Shuu-Jiun Wang ◽  
Artemio A Roxas ◽  
Bibiana Saravia ◽  
Byung-Kun Kim ◽  
Debashish Chowdhury ◽  
...  
Keyword(s):  
Latin America ◽  
Middle East ◽  
Primary Endpoint ◽  
Episodic Migraine ◽  
Acute Migraine ◽  
Efficacy And Safety ◽  
Medication Treatment ◽  
Significant Difference ◽  
Specific Medication ◽  
Secondary Endpoints

Objective EMPOwER, a double-blind, randomised, phase 3 study, evaluated the efficacy and safety of erenumab in adults with episodic migraine from Asia, the Middle East, and Latin America. Methods Randomised patients (N = 900) received monthly subcutaneous injections of placebo, erenumab 70 mg, or 140 mg (3:3:2) for 3 months. Primary endpoint was change from baseline in monthly migraine days at Month 3. Other endpoints included achievement of ≥50%, ≥75%, and 100% reduction in monthly migraine days, change in monthly acute migraine-specific medication treatment days, patient-reported outcomes, and safety assessment. Results At baseline, mean (standard deviation) age was 37.5 (9.9) years, 81.9% were women, and monthly migraine days was 8.2 (2.8). At Month 3, change from baseline in monthly migraine days (primary endpoint) was −3.1, −4.2, and −4.8 days for placebo, erenumab 70 mg, and erenumab 140 mg, respectively, with a statistically significant difference for erenumab versus placebo (P = 0.002 [70 mg], P < 0.001 [140 mg]). Both erenumab doses were also significantly superior to placebo on all secondary endpoints, including the proportion of patients achieving ≥50% reduction from baseline in monthly migraine days, change from baseline in monthly acute migraine-specific medication treatment days and change from baseline in the Headache Impact Test-6™ scores. The safety profile of erenumab was comparable with placebo; no new safety signals were observed. Conclusions This study of erenumab in patients with episodic migraine from Asia, the Middle East, and Latin America met all primary and secondary endpoints. A consistent numerical benefit was observed with erenumab 140 mg versus erenumab 70 mg across all efficacy endpoints. These findings extend evidence of erenumab’s efficacy and safety to patients under-represented in previous trials. ClinicalTrials.gov identifier: NCT03333109

scholarly journals 096 Assessment of the efficacy of erenumab during the open-label treatment (13–24 weeks) of subjects with episodic migraine who failed 2–4 prior preventive treatments: results of the LIBERTY study

2019 ◽  
Vol 90 (e7) ◽  
pp. A31.1-A31
Author(s):  
Lauren Giles ◽  
Uwe Reuter ◽  
Peter Goadsby ◽  
Michel Lanteri-Minet ◽  
Peggy Hours-Zesiger ◽  
...  
Keyword(s):  
Treatment Phase ◽  
Preventive Treatment ◽  
Episodic Migraine ◽  
Open Label ◽  
Double Blind ◽  
Open Label Extension ◽  
Specific Medication ◽  
Continuous Use ◽  
To Receive ◽  
Headache Impact

IntroductionTo assess efficacy of erenumab in the first three months of the open-label extension phase (OLEP; 13–24 weeks) of the LIBERTY study.MethodsIn the double-blind treatment phase (DBTP), 246 patients were randomized to placebo and erenumab 140 mg for 12 weeks, following which, patients completing that phase (N=240) were enrolled in OLEP, to receive monthly erenumab 140 mg. Outcomes measured monthly throughout to week 24 were achievement of at least 50%/75%/100% reduction in monthly migraine days (MMD), change from DBTP baseline in MMD, monthly acute migraine-specific medication days (MSMD), Headache Impact Test (HIT-6TM) total score, everyday activities (EA) and physical impairment (PI) as measured by the Migraine Physical Function Impact Diary (MPFID).ResultsOverall, 228/240(95.0%) patients completed the 24 week visit of the OLEP. In the overall population at Week 24, 39.2%, 15.9% and 7.0% patients achieved ≥50%/≥75%/100% reduction in MMD. The mean (standard deviation) change from DBTP baseline in MMD was −2.7(4.4) and −1.4(3.0) in MSMD; and −7.6(8.0), −2.5(9.2) and −4.0(9.0) in HIT-6TM, MPFID-PI and MPFID-EA scores respectively. Patients with continuous use of erenumab showed sustained efficacy in all outcomes assessed. Patients who switched from placebo to erenumab in the OLEP showed improvement from the first measurement at Week 16 on all outcomes assessed.ConclusionsEfficacy of erenumab was sustained throughout 24 weeks in a hard to treat patient population with multiple prior preventive treatment failures. Overall, efficacy data over 24 weeks (assessed over weeks 13–16,17–20 and 21–24) was generally in line with prior erenumab trials.

scholarly journals Efficacy and safety of galcanezumab for prevention of migraine headache in Japanese patients with episodic migraine: A phase 2 randomized controlled clinical trial

2020 ◽  
Vol 3 ◽  
pp. 251581632093257 ◽  
Author(s):  
Fumihiko Sakai ◽  
Akichika Ozeki ◽  
Vladimir Skljarevski
Keyword(s):  
Migraine Headache ◽  
Japanese Patients ◽  
Episodic Migraine ◽  
Secondary Outcome ◽  
Controlled Study ◽  
Controlled Clinical Trial ◽  
Life Questionnaire ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Secondary Endpoints

Objective: This study was designed to assess the efficacy and safety of galcanezumab in comparison with placebo for the prevention of migraine in Japanese patients with episodic migraine. Methods: In this double-blind, placebo-controlled study, which was conducted over 6 months, randomized adult patients received subcutaneous injections of galcanezumab (120 mg n = 115, 240 mg n = 114) or placebo ( n = 230) once monthly. The primary endpoint was the overall mean change from baseline in the number of monthly migraine headache days. The key secondary outcome measures were response rates (≥50%, ≥75%, and 100%); the Migraine-Specific Quality-of-Life Questionnaire Role Function-Restrictive score; monthly migraine headache days requiring acute treatment; and Patient Global Impression of Severity (PGI-S). Results: The mean change from baseline in monthly migraine headache days over months 1–6 was significantly ( p < 0.001) greater for the 120-mg galcanezumab dose (−3.60 days) and the 240-mg galcanezumab dose (−3.36 days) compared with placebo (−0.59 days). Both the 120-mg and 240-mg doses of galcanezumab were superior compared with placebo for each of the key secondary endpoints except for PGI-S (only the 240-mg dose was superior). The most commonly reported treatment-emergent adverse events were local injection-site reactions; erythema, swelling, pruritus, and pain were more commonly reported by patients who were treated with galcanezumab than those treated with placebo. Conclusion: The number of monthly migraine headache days was reduced with both doses of galcanezumab, and both doses were safe and well tolerated in Japanese patients with episodic migraine.

scholarly journals Two-year efficacy and safety of erenumab in participants with episodic migraine and 2–4 prior preventive treatment failures: results from the LIBERTY study

2021 ◽  
pp. jnnp-2021-327480
Author(s):  
Michel Dominique Ferrari ◽  
Uwe Reuter ◽  
Peter J Goadsby ◽  
Gabriel Paiva da Silva Lima ◽  
Subhayan Mondal ◽  
...  
Keyword(s):  
Treatment Phase ◽  
Preventive Treatment ◽  
Episodic Migraine ◽  
Responder Rate ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Open Label Extension ◽  
Registration Number

ObjectiveTo evaluate individual and group long-term efficacy and safety of erenumab in individuals with episodic migraine (EM) for whom 2–4 prior preventatives had failed.MethodsParticipants completing the 12-week double-blind treatment phase (DBTP) of the LIBERTY study could continue into an open-label extension phase (OLEP) receiving erenumab 140 mg monthly for up to 3 years. Main outcomes assessed at week 112 were: ≥50%, ≥75% and 100% reduction in monthly migraine days (MMD) as group responder rate and individual responder rates, MMD change from baseline, safety and tolerability.ResultsOverall 240/246 (97.6%) entered the OLEP (118 continuing erenumab, 122 switching from placebo). In total 181/240 (75.4%) reached 112 weeks, 24.6% discontinued, mainly due to lack of efficacy (44.0%), participant decision (37.0%) and adverse events (AEs; 12.0%). The ≥50% responder rate was 57.2% (99/173) at 112 weeks. Of ≥50% responders at the end of the DBTP, 36/52 (69.2%) remained responders at ≥50% and 22/52 (42.3%) at >80% of visits. Of the non-responders at the end of the DBTP, 60/185 (32.4%) converted to ≥50% responders in at least half the visits and 24/185 (13.0%) converted to ≥50% responders in >80% of visits. Change from baseline at 112 weeks in mean (SD) MMD was −4.2 (5.0) days. Common AEs (≥10%) were nasopharyngitis, influenza and back pain.ConclusionsEfficacy was sustained over 112 weeks in individuals with difficult-to-treat EM for whom 2–4 prior migraine preventives had failed. Erenumab treatment was safe and well tolerated, in-line with previous studies.Trial registration numberNCT03096834

scholarly journals Eptinezumab in episodic migraine: A randomized, double-blind, placebo-controlled study (PROMISE-1)

Cephalalgia ◽  
2020 ◽  
Vol 40 (3) ◽  
pp. 241-254 ◽  
Author(s):  
Messoud Ashina ◽  
Joel Saper ◽  
Roger Cady ◽  
Barbara A Schaeffler ◽  
David M Biondi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Primary Endpoint ◽  
Preventive Treatment ◽  
Episodic Migraine ◽  
Controlled Study ◽  
Upper Respiratory Tract ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Parallel Group ◽  
Study Sites

Objective To evaluate the efficacy and safety of eptinezumab, a humanized anti-calcitonin gene-related peptide monoclonal antibody, in the preventive treatment of episodic migraine. Methods The PRevention Of Migraine via Intravenous ALD403 Safety and Efficacy-1 (PROMISE-1) study was a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Adults with episodic migraine were randomized to eptinezumab 30 mg, 100 mg, 300 mg, or placebo for up to four intravenous (IV) doses administered every 12 weeks. The primary endpoint was change from baseline in monthly migraine days (MMDs) over weeks 1–12. Results A total of 888 patients received treatment across 84 study sites. Mean MMDs at baseline was ∼8.6 across treatment groups. Eptinezumab 100 mg and 300 mg met the primary endpoint, significantly reducing MMDs across weeks 1–12 compared with placebo (30 mg, −4.0; 100 mg, −3.9, p = 0.0182; 300 mg, −4.3; placebo, −3.2, p = 0.0001). Treatment-emergent adverse events were reported by 58.4% (30 mg), 63.2% (100 mg), 57.6% (300 mg), and 59.5% (placebo) of patients. Treatment-emergent adverse events reported by ≥2% of eptinezumab-treated patients at an incidence greater than placebo included: upper respiratory tract infection (30 mg, 11.4%; 100 mg, 9.9%; 300 mg, 10.3%; placebo, 7.2%), and fatigue (30 mg, 2.3%; 100 mg, 3.6%; 300 mg, 3.6%; placebo, <1%). Conclusion Eptinezumab (100 mg or 300 mg) significantly reduced migraine frequency, was well tolerated, and had an acceptable safety profile when used for the preventive treatment of migraine in adults with episodic migraine. ClinicalTrials.gov identifier: NCT02559895

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