LEVADEX™ for the Potential Treatment
of Migraine
LEVADEX orally inhaled migraine therapy is a novel migraine therapy in Phase 3 development. Patients administer LEVADEX themselves using the company's proprietary TEMPO® inhaler. LEVADEX has been designed to be differentiated from existing migraine treatments. It is a novel formulation of dihydroergotamine (DHE), a drug used intravenously in clinical settings to effectively and safely treat migraines. Based on clinical results, the company believes that LEVADEX has the potential to provide both fast onset of action and sustained pain relief and other migraine symptom relief in an easy-to-use and non-invasive at-home therapy.
In the efficacy portion of our first Phase 3 clinical trial, LEVADEX met all four primary endpoints, showing statistically significant improvement in pain relief, freedom from phonophobia (sensitivity to sound), freedom from photophobia (sensitivity to light) and freedom from nausea. Additional endpoints showed that LEVADEX provided rapid and sustained pain relief for up to 48 hours after dosing.
Migraine Headaches: A Debilitating Neurological Disorder
According to the National Headache Foundation (NHF), approximately 30 million people in the United States suffer from migraine, a chronic and debilitating neurological disorder. Common symptoms of migraine include recurrent headaches, nausea, vomiting, phonophobia and photophobia. According to NHF, most migraines last between four and 24 hours, but some last as long as three days. On average, migraine sufferers experience 1.5 migraine attacks monthly, although 25 percent of them experience one or more attacks weekly, according to published studies. The economic burden of migraine remains substantial despite existing treatments, with the direct and indirect costs of migraine in the United States estimated at over $20 billion annually.
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, migraine patients report that currently approved drugs do not fully meet their needs due to:
- Slow onset of action and short duration of effect: 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.
- Inconsistent response: Approximately 30 to 40 percent 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. Nasal delivery may lead to inconsistent dosing for many reasons, including difficulties in administration and poor absorption.
- Unacceptable side effect profiles: 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: LEVADEX
LEVADEX is designed to incorporate the multiple beneficial mechanisms of action that allow DHE to block initiation of migraine, limit pain, reduce inflammation and stop a migraine at any point in the migraine cycle. Based on research to date, including the FREEDOM-301 trial, the company believes the unique pharmacokinetic profile of LEVADEX has the potential to effectively treat migraines, while minimizing the side effects commonly seen with DHE and other currently available medicines.
Based on our clinical studies, we believe LEVADEX may provide patients with the following benefits when compared to existing migraine therapies:
- Rapid and long-lasting relief: In our Phase 3 trial, treatment with LEVADEX provided significant pain relief in as fast as 30 minutes. While not statistically significant, 50 percent more of the patients receiving LEVADEX than the patients receiving placebo reported pain relief at 10 minutes in our Phase 3 trial. In Phase 3, LEVADEX also provided pain relief for up to 48 hours.
- Broadly efficacious: Based on historical DHE use, LEVADEX 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: LEVADEX is non-injectable and easy to use, resulting in increased patient comfort and compliance. Our Phase 2 and 3 trials were performed in the home, without clinical supervision and with minimal training. Administration of LEVADEX allows for consistent dosing directly to the lung with fast and accurate systemic absorption.
- Low side effects: In our Phase 2 and 3 trials to date, treatment with LEVADEX was well-tolerated, with no serious adverse events reported. Drug-induced nausea was low and migraine-associated nausea also decreased with treatment.