• Proportion of subjects completing the treatment period at Month 12 on the initially assigned treatment [ Time Frame: Month 12 ]
  To evaluate the effect of erenumab compared to oral prophylactics on overall subject retention defined as % subjects completing treatment period at Month 12 on initially assigned treatment
• Cumulative average change from baseline on the monthly migraine days during the treatment period for subjects on the initially assigned treatment (Months 1-12) [ Time Frame: Month 12 ]
  To evaluate the effect of erenumab compared to oral prophylactics on the change from baseline in monthly migraine days during the treatment period
• Proportion of responders (PGI-I score greater than or equal to 5) as measured by PGIC at month 12 for subjects completing the treatment period at Month 12 on initially assigned treatment [ Time Frame: Month 12 ]
  To evaluate the effect of erenumab compared to oral prophylactics on the subject's assessment of the change in clinical status since the start of treatment as measured by the Patients' Global Impression of Change (PGIC) Scale

• Proportion of subjects completing the study at Month 12 on the randomized treatment [ Time Frame: Month 12 ]
  To evaluate the effect of erenumab compared to oral prophylactic(s) on overall subject retention defined as % subjects completing study on randomized treatment
• Cumulative average change from baseline on the monthly migraine days during the treatment period (Months 1-12) [ Time Frame: Month 12 ]
  To evaluate the effect of erenumab compared to oral prophylactic(s) on the change from baseline in monthly migraine days during the treatment period
• Proportion of responders as measured by PGIC at month 12 on the randomized treatment [ Time Frame: Month 12 ]
  To evaluate the effect of erenumab compared to oral prophylactic(s) on the subject's assessment of the change in clinical status since the start of treatment as measured by the Patients' Global Impression of Change (PGIC) Scale

• Drug: Erenumab
  Erenumab Dose 1 / Dose 2 Treatment Period 52 weeks
• Drug: Oral Prophylactic
  SoC oral prophylactic (active comparator) Treatment Period 52 weeks

• Experimental: Erenumab
  Escalate to Erenumab Dose 2 OR Switch to Oral prophylactic
  Interventions:

  • Drug: Erenumab
  • Drug: Oral Prophylactic
• Active Comparator: Oral Prophylactic
  Switch Oral Prophylactic
  Intervention: Drug: Oral Prophylactic

Inclusion Criteria:

• Written informed consent must be obtained before any assessment is performed
• Adults greater than or equal to 18 years of age upon entry into screening.
• Documented history of migraine (with or without aura) greater than or equal to 12 months prior to screening according to the International Classification of Headache Disorders-3rd Edition (ICHD-3).
• Greater than or equal to 4 and less than 15 days per month of migraine symptoms (based on ICHD-3 criteria) on average across 3 months prior to screening based on retrospective reporting.
• Less than 15 days per month of headache symptoms (i.e., migraine and non-migraine).
• Subjects in need for switching by documented failure of 1 or 2 prophylactic treatments in the last 6 months due to either lack of efficacy or poor tolerability. For subjects with 1 prior treatment failure, the failure should have occurred in the last 6 months. For subjects with 2 prior treatment failures, the second treatment failure should have occurred in the last 6 months.
• During baseline: Confirmed migraine frequency of 4 to 14 migraine days and less than 15 days of headache symptoms.
• During baseline: greater than or equal to 80% compliance with the headache diary.

Exclusion Criteria:

• Subjects meeting any of the following criteria are not eligible for inclusion in this study.

  • Older than 50 years of age at migraine onset.
  • History of cluster headache or hemiplegic migraine headache.
  • Unable to differentiate migraine from other headaches.
  • Lack of efficacy or poor tolerability with greater than 2 treatments from the 7 medication categories for prophylactic treatment of migraine after an adequate therapeutic trial.
• Efficacy failure is defined as no meaningful reduction in headache frequency, duration, and/or severity after administration of the medication for at least 6 weeks at the generally accepted therapeutic dose(s) based on the investigator's assessment.
• Tolerability failure is defined as documented discontinuation due to adverse events of the respective medication during the last 6 months prior to screening
• The following scenarios do not constitute lack of therapeutic response:
• Lack of sustained response to a medication

• Patient decision to halt treatment due to improvement

  • Used a prohibited medication, device, or procedure within 2 months.
  • Exposure to botulinum toxin in the head and/or neck region within 4 months.
  • Taken the following for any indication in any month during the 2 months prior to the start of the baseline period:
  • Ergotamines or triptans on greater than or equal to 10 days per month, or Simple analgesics (non-steroidal anti-inflammatory drugs [NSAIDs], acetaminophen) on greater than or equal to 15 days per month, or
  • Opioid- or butalbital-containing analgesics on greater than or equal to 4 days per month.
  • History of major psychiatric disorders (such as schizophrenia or bipolar disorder) or current evidence of depression. Subjects with anxiety disorder and/or major depressive disorders are permitted in the study if they are considered by the investigator to be stable and are taking no more than 1 medication for each disorder. Subjects must have been on a stable dose within the 3 months prior to the start of the baseline period.
  • History of seizure disorder or other significant neurological conditions other than migraine. Note: a single childhood febrile seizure is not exclusionary.
  • History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
  • History or evidence of any other unstable or clinically significant medical condition or clinically significant vital sign, laboratory, or electrocardiogram (ECG) abnormality during that could pose a risk to subject safety or interfere with the study evaluation.
  • Myocardial infarction, stroke, transient ischemic attack, unstable angina, or coronary artery bypass surgery or other re-vascularization procedures within 6 months prior to screening.
  • Score "yes" on item 4 or item 5 of the Suicidal Ideation section of the C-SSRS, if this ideation occurred in the past 6 months, or "yes" on any item of the Suicidal Behavior section, except for the "Non-Suicidal Self-Injurious Behavior" (item also included in the Suicidal Behavior section), if this behavior occurred in the past 2 years.
  • Evidence of drug or alcohol abuse or dependence within 12 months.
  • Pregnant or nursing (lactating) women
  • Women of child-bearing potential must use contraception during dosing with study treatment.
  • Use of other investigational drugs within 5 half-lives of enrollment, or until the expected pharmacodynamic effect has returned to baseline, whichever is longer.
  • History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes.
  • Human immunodeficiency virus (HIV) infection by history.
  • Previous exposure to erenumab or exposure to any other prophylactic CGRP-targeted therapy (prior to and during the study).