Table 4.
Current developmental pipeline in migraine
| Mechanism/Indication | Treatment | Current Stage |
|---|---|---|
| Calcitonin gene-related peptide (CGRP) mechanism antagonist | ||
| CGRP receptor antagonist (gepant) | Olcegepant (638) | Phase II |
| Telcagepant-acute (396) | Phase II* | |
| Telcagepant-preventive (394) | Phase II | |
| Rimagepant (561) | Phase II | |
| BI44370TA (216) | Phase II* | |
| MK-3207 (391) | Phase II | |
| Ubrogepant (828) | Phase II | |
| Atogepant (AGN-241689) (preventive)+ | Phase I | |
| CGRP antibody (nezumab) | Eptinezumab (224) | Phase III |
| Galcanezumab (225) | Phase III | |
| Fremanezumab (96, 97) | Phase III | |
| CGRP receptor antibody (numab) | Erenumab (770) | Phase III |
| Serotonin related | ||
| Serotonin 5-HT1F receptor agonist (ditan) | Lasmiditan (260, 267) | Phase III |
| Nitric oxide synthase (NOS) inhibition | ||
| Pan NOS | 546C88 (507) | Phase II |
| Inducible NOS | ||
| GW274150 acute (649) | Phase II (F) | |
| GW274150 preventive (403) | Phase II (F) | |
| Neuronal NOS plus triptan | NXN-188 (428, 595) | Phase II (F) |
| Glutamatergic targets | ||
| NMDA receptor migraine with prolonged aura | Ketamine (10) | Phase II |
| Prevention of aura not headache | Tonabersat (326, 381) | Phase II |
| AMPA/kainate | Tezampanel/LY293558 (704) | Phase II |
| iGluR5 (kainate) receptor | LY466195 (448) | Phase II |
| mGluR5 (glurants) | ADX10059 (839) | Phase II |
| AMPA receptor antagonist | BGG492 (353) | Phase II (F) |
| Neuroinflammatory targets | ||
| TRPV1 | SB-705498 (165) | Phase II (F) |
| Substance P/neurokinin-1 | Dapitant (218) | Phase II (F) |
| Lanepitant (351) | Phase II (F) | |
| GR205171 (176) | Phase II (F) | |
| Fosaprepitant (629) | Phase II (F) | |
| Lanepitant (349) Prevention | Phase II (F) | |
| Neurogenic plasma protein extravasation (PPE) | CP-122,288 (691) | Phase II (F) |
| 4991W93 (233) | Phase II (F) | |
| Other targets | ||
| Orexin 1 and 2 receptors (rexants) | Fliorexant (150) | Phase II (F) |
| Angiotensin receptor (?) | Candesartan (765, 800) | Off-License (F) |
| Telmisartan (219) | ||
| Emerging targets | ||
| Acid sensing ion channel (ASICs) | Amiloride (406) | |
| Pituitary adenylate cyclase activating peptide (PACAP) | PACAP receptor antagonists (17, 41, 874) | |
| Neuronal NOS | Neuronal NOS inhibition (310) | |
| Phosphodiesterase inhibition | Ibudilast (514) | |
| Neuromodulation strategies | ||
| Transcranial magnetic stimulation (TMS) | Single-pulse TMS (94, 537) | Marketed |
| Occipital nerve stimulation (ONS) | Chronic migraine (538, 705, 735) | Phase II (F) |
| Transcutaneous vagal nerve stimulation | Gammacore device (327, 736) | Phase II (F) |
| Supraorbital nerve stimulation | Cefaly (711) | Marketed |
| Sphenopalatine ganglion stimulation | ATI device (NCT01540799) | Phase II |
(F), study failed;
*
Liver toxicity led to termination of development. +Reported to exist in November 2015 at Allergan R&D Day. [Modified from Goadsby (306).]