The U.S. Food and Drug Administration approved 59 new drugs in 2018 – a 30% increase over the number approved in 2017 and a 270% increase over the low-water mark set in 2016. Only 7 of the new approvals were for drugs used in neurology; there were no approvals of psychiatric agents.

The hottest area in neurology was drugs used for migraine prophylaxis with three calcitonin gene-related peptide (CGRP) antagonists receiving the nod in the U.S. The first was Aimovig (erenumab, Novartis), a monoclonal antibody that targets the CGRP receptor; it is administered subcutaneously once-monthly. Aimovig also received approval by Health Canada in May.

The field soon became competitive with two other MAbs, both of which target the CGRP ligand, receiving approval in the U.S. (but not in Canada) in September. Ajovy (fremanezumab, Teva) is administered subcutaneously either once-monthly or once every three months. Emgality (galcanezumab, Eli Lilly) is administered subcutaneously once-monthly.  In late-stage development but unapproved are an infusion drug, eptinezumab (Alder), and the oral CGRP antagonists ubrogepant and rimegepant for acute migraine (for a review see Holland & Goadsby. Neurotherapeutics 2018;15:304-312; free full text at www.ncbi.nlm.nih.gov/pmc/articles/PMC5935646/pdf/13311_2018_Article_617.pdf).

Epidiolex (cannabidiol, Greenwich Research) was approved in June as an antiseizure add-on therapy for patients with Lennox-Gastaut syndrome and Dravet syndrome. The drug is a liquid solution taken twice-daily in combination with other antiseizure medications. Approval was based on the results of three efficacy trials (Devinsky et al. N Engl J Med 2018;378:1888-1897; Thiele et al. Lancet 2018;391:1085-1096; Devinsky et al. N Engl J Med 2017;376:2011-2020). Epidiolex is the first cannabinoid drug and the first treatment for Dravet syndrome to be approved in the U.S.

However, two months later, the FDA approved a second drug for Dravet syndrome, Diacomit (stiripentol, Biocodex) for use in combination with clobazam. Diacomit was approved in Canada in 2012 as an add-on to clobazam and valproate in patients with severe myoclonic epilepsy in infancy (SMEI) and Dravet syndrome.

Another FDA first was Onpattro (patisiran, Alnylam Pharmaceuticals) – the first small interfering RNA (siRNA) agent and the first therapy to receive approval for the treatment of polyneuropathy caused by hereditary transthyretin-mediated amyloidosis (hATTR). For Onpattro, siRNA is encased in a lipid nanoparticle and delivered by infusion to the liver, where it halts production of abnormal amyloid protein that would otherwise accumulate in peripheral nerves. hATTR is an orphan disease with an estimated 50,000 cases worldwide. A second drug for hATTR patients, Tegsedi (inotersen, Akcea Theraps), also received approval in the U.S. and Canada. Tegsedi is a transthyretin-directed antisense oligonucleotide indicated for the treatment of the stage 1 or 2 polyneuropathy in adults with hATTR.