Migraine is the most prevalent brain disorder in the world, and yet, until earlier this year, the options for preventative treatment only included a variety of off-label drugs or drugs repurposed from other indications. The result is that many of these preventative therapies had poor efficacy profiles, and on top of this, poor safety and tolerability profiles meant that even fewer patients were adequately managed. These patients, who have tried more than one preventative therapy and failed to see improvement are largely defined as refractory patients, and they represent a major underserved population in the migraine market. Indeed, in some cases, migraines can worsen, with 2.5% of patients progressing from episodic migraine (four to 14 migraines per month) to chronic migraine (15+ migraines per month).
Eli Lilly, which has an active pipeline with respect to migraine drugs, conducted a study analysing migraine patients on preventative therapies to try to understand the burden on patients who discontinue medication over a 12-month period and compared that to patients who persisted with their therapies. The study included 55,000 patients split across four arms: those that persisted, those that changed medication once, changed medication twice, and changed medication three times.
The study showed that only 20% of patients persisted throughout the year with their originally prescribed therapy, with 70% changing once, 10% changing twice, and <1% changing three times. Unsurprisingly, the study showed that the more a patient changes medication, the higher the cost and thus the greater the economic burden. Rather more surprisingly, the study showed that the distribution of the prescribing physician does not change throughout the four patient groups; roughly 35% of patients from each group were treated by primary care physicians, 35% by neurologists or headache specialists, and 30% by other physicians. These findings suggest that the most difficult-to-treat patients, who have switched medication multiple times, are still being treated by primary care physicians when in reality they should be treated by specialists, pointing to a problem in the referral system and potential for improvement.
However, the latest class of drugs to be approved in the migraine field – CGRP monoclonal antibodies (mAbs) – have shown that times are changing for preventative therapies. Clinical trials in chronic migraine have shown that CGRP mAbs significantly improve the burden of migraine. Results show that, in refractory patients who have failed two previous medications, 50% responder rates for patients receiving the drugs are 30.4%, compared to 9.4% in the placebo group. The number of migraine days each migraineur experiences is also improved, with 1.3 fewer migraine days in the placebo group compared to 5.8 fewer migraine days in the CGRP mAb group. On top of this, safety results show the most common adverse events associated with CGRP mAb’s is injection site pain, a mild event compared to other preventive therapies.
Ultimately, patients that suffer from migraine have been inadequately managed for decades, with preventative therapies that have poor efficacy and safety profiles for first line treatments, which has led to high economic and social burdens for patients. However, the new CGRP mAbs have hugely improved the outlook of migraine patients, particularly those that are refractory, and have begun to address once of the largest unmet needs in the market.