An independent review of current treatments for migraine

Here we look at the options and review some of the most recent advances.

Missed our previous edition for the Migraine series? Review the epidemiology and pathophysiology here or look at the final part which will looks at treatments on the horizon and the molecules in early clinical trials here.

Non-specific drugs

Current treatments include non-specific drugs such as analgesics and non-steroidal anti-inflammatories, as well as ergot derivatives and triptans which work by vasoconstriction and inhibition of neurotransmitter release. The latter includes the now generic almotriptan, zolmitriptan and frovatriptan, which were first approved about 20 years ago.

However Dr Reddy/Promius Pharma have developed intranasal and injectable forms of triptan: Tosymra (sumatriptan intranasal) - otherwise known as DFN 02 - was FDA approved on 8 January 2019 for acute migraine and Zembrace Sym Touch (sumatriptan injection) – known as DFN 11 – which was FDA approved in 2016 for the same indication. Although Dr Reddy has now sold the global rights to Tosymra and Zembrace Sym Touch to Upsher Smith for $70 million, the company retains a migraine portfolio with DFN 15 (a liquid formulation of celecoxib) and DFN 19 (dihydroergotamine nasal spray).

Despite variation in methods of delivery such as nasal spray and transdermal patch, headache recurrence can occur in up to 40 % of patients taking triptans, and the drugs can have a variety of side-effects such as paraesthesias [Ref 1]. The now generic anti-epileptic drug Topamax (topiramate), from Janssen, is also widely used though its exact mechanism in migraine prevention is not understood. In addition, studies show that nearly 1 in 5 people with migraine are currently using opioids to treat their disease, which can lead to addiction problems.

Calcitonin gene-related peptide (CGRP) inhibitors

Undoubtedly the most exciting migraine therapy development in recent years has been with calcitonin gene-related peptide (CGRP) inhibitors. Analysts suggest that CGRP inhibitors could account for nearly half ($4.5 billion) of the migraine drug market by 2025.

Aimovig (erenumab) from Amgen/Novartis is a CGRP receptor antagonist monoclonal antibody approved in both EU and US in 2018. Phase III STRIVE data shows that 55% of patients on Aimovig 140 mg experienced at least a halving in the number of monthly migraine days requiring acute medication at week 52. Aimovig also provides sustained efficacy in the prevention of episodic migraine – headaches occurring on less than 15 days per month. Despite study results, England’s NICE has rejected its use, arguing that there is insufficient evidence that Aimovig is cost effective compared to other treatments in chronic migraine.

Another monoclonal antibody CGRP receptor antagonist, Ajovy (fremanezumab) from Teva, was first approved in 2018. Ajovy is prescribed in two options monthly in subcutaneous injection or three monthly in three subcutaneous injections. Phase III studies show reductions from baseline in monthly days with migraine, moderate to severe headache, or use of acute headache medications were about 3.5 days (30 per cent) greater with fremanezumab than with placebo. Its long half-life, target specificity and pharmacokinetic profiles, including lack of hepatic metabolism and limited potential for drug interaction, may address substantial unmet needs for the prevention of frequent episodic migraines, as well as chronic migraines – defined as attacks that occur on more than 15 days per month. 

Not surprisingly, high frequency episodic migraine shares many similarities with chronic migraine. Patients with this condition are at a high risk of transformation to chronic migraine. So far there is only one FDA approved drug for the prevention of chronic migraine: Botox (onabotulinumtoxin A) from Allergan/Abbvie which was FDA approved in 2010. Head-to-head data from a study in chronic migraine demonstrated that Botox had a more favourable tolerability profile than topiramate. Of patients randomised to receive topiramate, 50.7% of patients discontinued treatment due to adverse events, compared to 3.6% of patients randomised to receive onabotulinumtoxin A. Findings also show a significantly higher number of patients reported at least a 50% reduction in headache frequency when treated with Botox.

Emgality (galcanezumab) from Eli Lilly was FDA approved in 2019.  It is another calcitonin gene-related peptide (CGRP) indicated in adults for the preventive treatment of migraine but also for the treatment of episodic cluster headache. In the Phase III CONQUOR study, treatment with Emgality reduced monthly migraine headache days by 4.1 days compared with 1.0 day with placebo in the total (chronic and episodic migraine) study population. In EVOLVE-1 and EVOLVE-2 studies for episodic and chronic migraine, Emgality produced a 50 % reduction in 60% of patients versus 36%-39% on placebo. In the REGAIN study Emgality showed a 50% reduction in around 28% of patients.

Reference
“Recent advances in migraine therapy” Fabio Antonaci et al. Springerplus, 2016 May 17. doi: 10.1186/s40064-016-2211-8.