Migraine is a neurological disorder and is a major public health problem as it is the third most common disease in the world with an estimated global prevalence of 1 in 7 people.1 According to the Migraine Research Foundation, migraine affects more than 30 million men, women and children in the United States. Migraine is more common in women, with about 18% of women and 6% of men affected. Migraine prevalence is highest during the peak productive ages of 25 to 55, which results in high costs to employers and managed care organizations.
Migraine attacks are associated with varying degrees of headache pain (mild to severe) with accompanying symptoms of sensitivity to light and sound and often with nausea and vomiting. In addition to the attack-related disability, many sufferers also fear knowing that at any time an attack could disrupt their ability to work, go to school, care for their families, or enjoy social activities. More than 90% of sufferers are unable to work or function normally during their migraine attacks.
Most migraines last between four and 24 hours, but some last as long as three days. According to published studies, 63% of migraine patients experience between one and four migraines per month.
Current therapies for migraine include general analgesics (aspirin, acetaminophen, and combinations of the ingredients), non-steroidal anti-inflammatories, and “migraine specific drugs,” including the triptans and ergots. According to a 2014 study by Global Data Pharma Point, sales of prescriptions for medications indicated for migraine in the United States were approximately $1.9 billion in 2012. Of this amount, $1.1 billion was for triptans.
In placebo-controlled clinical trials, these drugs have generally been effective (pain relief at 2 hours) in 60-70% of migraine attacks, but complete pain freedom is seen in a much smaller percentage of subjects (less than 30%). Another shortcoming of current treatments is recurrence of migraine and associated pain and symptoms within 24 to 48 hours of treatment, which contributes to the dissatisfaction with current migraine therapies.
Each of the currently available methods of administering triptans, including the oral tablet, nasal spray, subcutaneous injection and iontophoretic patch has significant disadvantages. Oral, nasal and iontophoretic patch triptan products are characterized by relatively slow onset of action, typically thirty minutes or more after ingestion or administration. Some migraine patients fail to respond consistently to oral triptans, and oral treatments may be ineffectual for patients who are suffering from nausea, vomiting and gastric stasis that can be associated with migraine.
Gastric stasis is common in migraine sufferers and results in slow gastrointestinal (GI) transit time of the migraine therapy, resulting in delayed time for the formulation to reach the duodenum or jejunem, where the drugs are typically absorbed.
For zolmitriptan tablets, it was shown that AUC0-4, and Cmax were significantly reduced during the migraine state, while Tmax was delayed 30 minutes compared to the non-migraine state.
Intranasal treatments are largely swallowed and often cause an unpleasant taste that may worsen nausea and vomiting. Only injectable sumatriptan has been shown to provide relief consistently at 10-30 minutes post-dosing. However, most migraine sufferers do not like giving themselves an injection because of the pain and discomfort associated with administration.
Several studies have shown that earlier treatment of a migraine can lead to a more successful outcome. However, to be a successful treatment, the medication must be absorbed into the systemic circulation and reach the site of action of the drug.2
The Zosano Pharma Solution
M207 is designed to provide:
- pain relief in the acute treatment of migraine with and without aura in as early as 20 minutes.
- rapid delivery of an efficacious dose using a stable formulation on a discreet transdermal adhesive.
- pain relief to patients who suffer from nausea caused by their migraines as it bypasses the GI tract.
If a product can produce onset of relief in a comparable time course as a sumatriptan injection, with a less-invasive, easy-to-use mode of delivery, that also bypasses the GI tract, it would offer migraine patients the much sought after fast relief and return to a fully functional state.
The Company believes that M207 has the potential to provide an attractive alternative to currently marketed triptan products for the acute treatment of migraine.
1 The Migraine Trust Foundation
2 Ahn AH and Basbaum AI 2005