Objectives: Migraine is a neurological disease with recurrent headache pain, accompanied by e. g. photophobia or nausea. Number of headache days classifies to episodic or chronic migraine (EM/CM). The anti-Calcitonin-Gene-Related-Peptide (CGRP) antibody fremanezumab offers a new type of prophylaxis. Methods: In two Phase-3-trials patients with CM or EM were randomized in 1:1:1 ratio to receive subcutaneous fremanezumab quarterly (single dose: 675 mg), fremanezumab monthly (HALO-CM/HALO-EM: 675/225 mg as loading dose and 225 mg at week 4/8) or placebo. During the German market access process, the Gemeinsamer Bundesausschuss (G-BA) defined different patient populations. G-BA defined the appropriate comparator therapy (ACT) for the population of untreated patients and those with inadequate response to at least one prior preventive migraine medications: propranolol/metoprolol, topiramate, amitriptyline or flunarizine. Placebo patients did not start the medication during the trial but were continuing their pre-existing medication (ACT). Results for placebo + ACT (n=49/45) vs. fremanezumab (quarterly n=322/256, monthly n=325/249) are presented. Results: Under fremanezumab, more EM as well as CM patients reached clinical meaningful reduction by $ 50 % of their monthly migraine days (EM quarterly: RRs = 3.06, p = 0.0015, monthly: 3.38, p = 0.0005, CM: 2.39, p = 0.0150, 2.61, p = 0.0073). A reduction of $ 50 % of monthly headache days of at least moderate severity was seen (EM: RRs = 2.92, p = 0.0010, 3.01, p = 0.0007, CM: 1.98, p = 0.0187, 2.23, p = 0.0054). Patients with CM used significantly less acute migraine-specific medication (Hedges' g =-0.56 [-0.868,-0.262]). In patients with EM, fremanezumab led to significantly less serious adverse events compared with patients taking ACT (RRs = 0.18, p = 0.0298, 0.12, p = 0.0187). Conclusions: Fremanezumab as migraine prophylaxis resulted in a lower frequency of headache compared to placebo along with beta-blockers, topiramate, amitriptyline or flunarizine.