Long-term treatment with galcanezumab in patients with chronic migraine: results from the open-label extension of the REGAIN study

Abstract

Background

Galcanezumab, a monoclonal antibody to calcitonin gene-related peptide, was found to be safe and efficacious for the preventive treatment of chronic migraine based on the randomized, placebo-controlled double-blind period of the REGAIN study. Long-term safety and efficacy were assessed in an open-label extension.

Methods

Patients 18–65 years old with chronic migraine completing the 3-month double-blind period of REGAIN could enter a 9-month open-label extension (OLE; months 4–12). Upon entering the OLE, patients received a 240-mg galcanezumab loading dose, then 120 mg at the next month, with flexible dosing thereafter (120 or 240 mg/month). The primary efficacy measure was the mean change in the number of monthly migraine headache days from double-blind baseline to month 12. Other endpoints included response rates (based on percent reduction in monthly migraine headache days from double-blind baseline to month 12), safety and tolerability.

Results

Of patients who completed double-blind treatment, 1022 (99%) entered the OLE, with 81% completing month 12. From a baseline of 19.4 monthly migraine headache days at the beginning of the double-blind period, patients at month 12 in the previous placebo, 120-mg, and 240-mg galcanezumab groups had a mean change of −8.5, −9.0, and −8.0, respectively (SE = 0.43 to 0.55, within-group p’s < .001). At month 12, the percentage of patients with ≥50% response was 57%, 57%, and 53%, respectively. Percentage with ≥75% response was 32%, 31%, and 30%, respectively. Percentage with 100% response was 8%, 6%, and 6%, respectively. There were no significant new safety findings during the open-label period. The incidence of discontinuation from the OLE due to adverse events was 5%.

Conclusion

Galcanezumab was effective, safe, and well-tolerated, with high adherence, for up to 12 months of treatment in patients with chronic migraine.

Trial Registration

Clinicaltrials.gov identifier: NCT02614261; www.clinicaltrials.gov/ct2/show/NCT02614261

Keywords:

• Galcanezumab
• open-label extension
• chronic migraine
• long-term
• CGRP
• preventive treatment

Transparency

Declaration of funding

This work was supported by Eli Lilly and Company. Eli Lilly and Company funded the study in a whole and its employees and assignees were involved in study design, data collection, data analysis, data interpretation, and writing of all related reports and publications. The corresponding author had full access to all study data and had final responsibility for the decision to submit for publication. Editorial assistance provided by Syneos Health was also funded by Eli Lilly and Company.

Declaration of financial/other relationships

HCD and LQL are full-time employees and minor stockholders of Eli Lilly and Company. SW is a full-time employee of Sarepta Therapeutics. SKA is an employee of Impel NeuroPharma. PPR has received honoraria as a speaker and consultant for Allergan, Amgen, Biohaven, Eli Lilly and Company, Medscape, Novartis, and Teva. She does not have stocks from any pharmaceutical company. UR has received honorarium for the participation in advisory boards, consultation or presentations from Allergan, Amgen, CoLucid, Electrocore, Eli Lilly and Company, Medscape, Novartis, StreaMedUp, and Teva. DD has received honoraria for the participation in advisory boards, consultation, or as a speaker from Novartis, Amgen, Eli Lilly and Company, and Teva. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Conception of the work: HCD, SW; Design of the work: HCD, SW; Data acquisition: PPR, UR, DD; Data analysis: SW; Interpretation of data: all authors (HCD, SW, PPR, UR, DD, LQL, SKA); Drafting of the manuscript: HCD; Critical revision of the manuscript for important intellectual content: all authors (HCD, SW, PPR, UR, DD, LQL, SKA).

Acknowledgements

The authors thank all the study participants, site investigators, and personnel involved in the REGAIN study. Editorial assistance was provided by Regina E. Burris (Syneos Health). Additional statistical support was provided by Hai-An Hsu (TechData Service Company).

Data availability statement

Lilly provides access to all individual participant data collected during the trial, after anonymization, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the United States and European Union and after primary publication acceptance, whichever is later. No expiration date of data requests is currently set once data are made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data sharing agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, blank or annotated case report forms, will be provided in a secure data sharing environment. For details on submitting a request, see the instructions provided at www.vivli.org.

Ethics statement

This study was reviewed and approved by appropriate institutional review boards and was conducted according to the Declaration of Helsinki. All participants gave written informed consent. The ethical review boards included Quorum Review, Inc., Dean Foundation for Health Research and Education, Baylor, Scott, & White, IRB Services, Montreal Neurological Institute and Hospital, West Midlands - Edgbaston REC, Isala Klinieken METC, Hospital Universitari Vall d'Hebron, Comitato Etico Irccs San Raffaele Pisana, Comitato Etico Interaziendale Bologna-IMOLA, Comitato Etico Area Vasta Centro Presso AOU, Comitato Etico della Provincia di Modena, Comitato Etico Ospedale San Raffaele, Eticka Komise IKEM a Thomayerovy Nemocnice, Eticka Komise Clintrial, s.r.o., Eticka Komise FN u sv. Anny v Brne, Ethikkommission der Landesärztekammer Hessen, Comite de Etica Independiente en Invest. Clinica Dr. C Barclay, Comite de Etica del Centro de Osteopatias Medicas, Sanatorio Allende-Cordoba, Instituto Reumatologico Strusberg, Hillel Yaffe Medical Center, Chaim Sheba Medical Center, Maccabi Healthcare Services, Kfar Saba, Tel Aviv Sourasky Medical Center, Chi-Mei Medical Center - Yung Kang, Institutional Review Board, Kaohsiung Medical University Chung-Ho Memorial Hospital, Sin-Lau Hospital, Taipei Veterans General Hospital, Institutional Review Board, Far Eastern Memorial Hospital, Research Ethics Review Committee, Grupo Médico CAMINO S.C., Hospital Angeles de Culiacan, Hospital Hispano S.A. de C.V.