MAP0004 for the Treatment of Migraine
MAP Pharmaceuticals is developing MAP0004 as a potential treatment for migraine. MAP0004 is an orally inhaled version of dihydroergotamine (DHE), self-administered via our proprietary Tempo® inhaler. DHE is available as an intravenous therapy which has been used in clinical settings for over 50 years to safely treat migraine. In our Phase 2 clinical trial, MAP0004 demonstrated the potential to be both fast acting and long-lasting, providing pain relief in as fast as ten minutes from dosing with relief lasting for at least 24 hours. In January 2008, we completed a special protocol assessment process with the FDA for our first Phase 3 clinical trial of MAP0004. We initiated our Phase 3 program in July 2008.
Migraine Headaches: A Debilitating Neurological Disorder
According to the National Headache Foundation, approximately 30 million people in the United States suffer from migraine, a chronic and debilitating neurological disorder characterized by episodic attacks often involving four symptoms: pain, nausea, phonophobia, or abnormal sensitivity to sound, and photophobia, or abnormal sensitivity to light. Approximately 18% of women and 6% of men in the United States are migraine sufferers. Migraine is known to limit the normal functioning of patients, who often seek dark, quiet surroundings until the episode has passed. Most migraines last between four and 24 hours, but some last as long as three days. According to published studies, the median frequency of attack is 1.5 times per month, although approximately 25% of migraine sufferers experience one or more attacks every week.
Limitations of Current Migraine Therapies
The type of migraine treatment pursued depends on frequency and severity of the headache, speed of onset and previous response to medication. Triptans are the class of drugs most often prescribed for migraine. Other forms of DHE are also available to migraine sufferers, including IV and nasal. However, the current therapies have the following major limitations:
- Slow onset: While triptans have improved the treatment of migraine, their onset of pain relief is relatively slow. Estimated onset of significant pain relief with oral triptans occurs between 45 and 90 minutes after dosing. Nasal administration of DHE generally takes 30 to 60 minutes to provide significant pain relief.
- Not broadly efficacious: Approximately 30% to 40% of migraine patients do not respond fully to the first triptan prescribed and many migraine sufferers do not respond to triptans at all. These patients currently have few satisfactory alternatives.
- Inconvenient and inconsistent dosing: Intravenous DHE results in rapid relief, but requires the supervision of a healthcare provider and is typically performed in a clinic or hospital setting, which is expensive and requires the patient to travel while suffering with migraine. Nasal delivery may lead to inconsistent dosing for many reasons, including difficulties in administration and poor absorption.
- Side effects: Triptans may constrict arteries, which may raise blood pressure. Nausea is a common side effect of intravenous DHE administration. Nasal administration of DHE may result in unpleasant taste, and can cause inflammation of the nasal membrane.
Our Potential Solution: MAP0004
MAP0004 is an orally inhaled, at-home therapy that patients can self-administer using our proprietary Tempo inhaler. In our Phase 2 clinical trial, MAP0004 retained the rapid onset and long-lasting effectiveness of intravenous DHE while avoiding the nausea that intravenous administration can cause. Based on our clinical studies, we believe MAP0004 may provide patients with the following benefits when compared to existing migraine therapies:
- Rapid onset:
AS FAST AS TEN MINUTES AND LONG LASTING In our Phase 2 trial, treatment with MAP0004 provided significant pain relief in as fast as ten minutes. MAP0004 also provided pain relief with low incidence of recurrence through at least 24 hours. - Broadly efficacious: Based on historical DHE use, MAP0004 may provide a higher response rate and has the potential to treat patients who have not previously responded to other therapies, such as triptans.
- Convenient and consistent delivery: MAP0004 is non-injectable and easy to use, resulting in increased patient comfort and compliance. Our Phase 2 trial was performed in the home, without clinical supervision and with minimal training. Administration of MAP0004 allows for consistent dosing directly to the lung with fast and accurate systemic absorption.
- Low side effects: In our Phase 2 trial, treatment with MAP0004 was well-tolerated, with no serious adverse events reported. Drug-induced nausea was low and migraine-associated nausea also decreased with treatment.