Migraine Indication

Migraine Overview

migraine acute or chronic headache need for painkiller or prevent painMigraine is a chronic neurological disease/disorder characterized by repeated moderate to severe headaches often in association with a number of autonomic nervous system symptoms. A migraine headache causes throbbing or pulsating pain, usually on only one side of the head. The word derives from the Greek ἡμικρανία (hemikrania), “pain on one side of the head.” Migraines may occur as often as several times per week or as rarely as once or twice a year and last between four hours and three days. Migraines are often associated with symptoms such as nausea, vomiting, and extreme sensitivity to light and sound. The pain is generally made worse by physical activity. Migraine headaches (often misdiagnosed as sinus or tension headaches) can interfere with sleep, work, and other everyday activities.

The exact causes of migraines are unknown, although they are related to changes in the brain as well as genetic causes. The primary theory is related to increased excitability of the cerebral cortex and abnormal control of pain neurons in the trigeminal nucleus of the brainstem. A migraine is triggered in the migraine “pain center” or generator of the brain when hyperactive nerve cells send out impulses to the blood vessels causing them to clamp down or constrict, followed by dilation (expanding) and the release of prostaglandins, serotonin, and other inflammatory substances that cause the pulsation to be painful.

Migraine Classification/Pathways

According to the International Classification of Headache Disorders, 2nd edition (ICHD-2, 2004), migraine is classified into two major subtypes:

  • Migraine with aura (classical migraine) – An affected location or function in the nervous system; focal neurological symptoms accompany the headache.
  • Migraine without aura (common migraine) – Clinical syndrome characterized by headache and associated symptoms.

Different pathways may contribute to migraine headaches, as explained by the following overview:

  • According to neural theory, hyperexcitability in the form of cortical spreading depression leads to migraine through a cascade involving inflammation and the sympathetic nervous system.
  • According to vascular theory, vascular disturbances (vasodilatation–vasoconstriction) lead to migraine attacks through a cascade involving inflammation and the serotonin system.

These pathways described in these alternative theories may overlap with key mechanisms that may activate neural inflammation and lead to migraine pain. The possibility of different pathways suggests that different medicines that target these alternative pathways may have differential efficacy.

Migraine-Overview

It is now believed that migraines are also caused by inherited abnormalities in certain areas of the brain.

Migraine: A Global Disease

Migraine headache is a common neurological condition:

  • Migraine headaches affect 10% to 20% of the global population
  • According to the American Migraine Study1, migraine affects approximately 30 million people in the US – and is expected to continue to grow2
  • Migraines affect people during their productive years (25 to 50 years of age) and are three times more common in women than men
  • Approximately 80% of patients report having a family history of migraines, with heritability estimates as high as 50%
  • Migraine is ranked by the WHO as number 19 among all diseases worldwide causing disability

Migraines are largely under-recognized, with only half of individuals with migraine aware of their condition and less than half of them ever diagnosed with migraine. According to recent research conducted by Foster Rosenblatt, the greatest unmet need is for patients who are either refractory to or for whom triptans are contraindicated (this could represent 20% to 30% of acute migraine sufferers).

Although migraine is not the most common headache disorder, it is the most commonly diagnosed condition in primary headache disorders. Patients with migraine episodes often present with nausea, vomiting, and visual disturbances, resulting in impaired quality of life, high medical need, and social burden. A migraine does not often cause disabling conditions, and therefore remains under-reported and under-diagnosed due to a large number of migraine sufferers relying on over-the-counter treatment instead of seeking medical advice.

The disease burden of migraine headache is significant and presents a major challenge to healthcare providers. Migraine prevalence is expected to increase by 0.6% across the seven major markets (the US, Japan, France, Germany, Italy, Spain, and the UK; the highest growth rate is expected in the US). The burden of migraine is considerable as it affects individuals during their reproductive and economically productive years resulting in over 100 million “bedridden days” per year. In the U.S. alone, the indirect annual cost of migraine in lost work productivity could be as high as $17 billion (http://www.headache-help.org/)

Migraine is hereditary, but can be highly affected by depression, stress, and hormonal fluctuations. Several co-morbidities are associated with migraine, mainly epilepsy, psychiatric disorders, and stroke.

Migraine Treatment Options

Migraine treatment options are either preventative or for acute (symptomatic/abortive) treatment. Migraine treatment is classified as:

  • prophylactic (chronic treatment of migraine)
  • intermittent prophylaxis (only when a migraine is expected, e.g., during menstruation)
  • symptomatic (abortive; acute rescue drugs used only during an attack)

Symptomatic therapy (currently triptans) is the mainstay of migraine management, with the goal of alleviating or decreasing symptoms. However, recent clinical studies have shown that excessive use of symptomatic medications on a daily basis may result in chronic migraines; thus, current prophylactic and symptomatic medications may ultimately become ineffective.

As a result, newer therapies that are not triptan-based represent a significant clinical unmet need. Our currently active drug development programs include acute migraine treatment, the lead pain program (TopofenTM, ELS-M11), currently in Phase IIa.