Migraine Medication Levadex - Awaiting FDA Approval, TEMPO Patent Granted
For many reasons, finding effective treatments is a common problem for people who have Migraine disease, both preventive treatments and the acute treatments we use when a Migraine attack occurs.
At this point, we're not seeing much in the way of totally new medications being developed for Migraine, BUT we are seeing some new delivery systems being developed for older medications, and the delivery system can make a big difference in if and how well a medication works for us.
Two issues that can significantly impact the medications we take when a Migraine occurs are vomiting and gastric stasis. Obviously, oral medications may not be very effective if patients vomit soon after taking them. There are also safety issues involved due to this problem because some Migraineurs have overdosed with their medications because they redosed after vomiting, not realizing that some of the medication had already been absorbed into their systems. Gastric stasis is delayed emptying of the stomach. Some research has indicated that gastric stasis can occur with Migraine and, in turn, leave medication in the stomach and unabsorbed.
One new Migraine abortive medication in development is Levadex (formerly MAP0004), developed by MAP Pharmaceuticals. Levadex is an orally inhaled form of dihydroergotamine, the same medication in D.H.E. 45 and migranal Nasal Spray. The oral inhalation delivery system delivers the medication through the lungs to the systemic circulation using MAP's proprietary TEMPO inhaler (see image on right).
There are several phases to clinical trials. We usually hear mostly about Phase III trials.
- Phase II trials are controlled clinical studies conducted to evaluate the effectiveness of the drug for a particular indication or indications in patients with the disease or condition under study and to determine the common short-term side effects and risks.
- Phase III trials are expanded controlled and uncontrolled trials after preliminary evidence suggesting effectiveness of the drug has been obtained, and are intended to gather additional information to evaluate the overall benefit-risk relationship of the drug and provide and adequate basis for physician labeling.
Phase II study of MAP0004 (before it was named Levadex):
This study showed:
- a statistically significant early onset of pain relief (10 minutes).
- meaningful sustained pain relief of up to 48 hours.
- a "favorable" side effects profile including lack of nausea and the concentration side effects often observed when D.H.E is administered IV.
The Phase III study of Levadex:
Also called FREEDOM-301, the Phase III study provided the additional date needed for MAP to submit a New Drug Application (NDA) to the United States Food and Drug Administration (FDA) in May of 2011. The NDA is still pending.
In the FREEDOM-301 study, the efficacy (the ability of a medication to produce the desired results) assessment focused on four major Migraine symptoms at the standard two-hour time point for such Migraine studies. All four co-primary endpoints (the overall outcomes that the study was designed to evaluate) for Levadex were met at two hours:
- Pain relief was observed in 59% of patients in the Levadex treatment group compared with 35% in the placebo group.
- Freedom from phonophobia (increased sensitivity to sound) was observed in 53% of patients in the Levadex treatment group compared with 34% for the placebo group.
- Freedom from photophobia (increased sensitivity to light) was observed in 47% of patients in the Levadex treatment group compared with 27% for the placebo group.
- Freedom from nausea was observed in 67% of patients in the Levadex treatment group compared with 59% for the placebo group.
Four secondary endpoints also were analyzed:
- Sustained pain relief from two to 24 hours was observed in 44% of patients in the Levadex treatment group compared with 20% for the placebo group.
- The statistically significant time to pain relief was calculated to be 30 minutes.
- Pain relief at four hours was observed in 65% of patients in the Levadex treatment group compared with 37% for the placebo group.
- The proportion of patients experiencing pain relief at 10 minutes, while not statistically significant, was 50% greater in the Levadex treatment group (9%) compared with the placebo group (6%).
Levadex was well tolerated, with no serious side effects reported during the study. The most common side effects reported were
- medication aftertaste: 6%, compared to 2% for placebo
- nausea: 5%, compared to 2% for placebo.
- triptan sensations such as chest discomfort (1%) and paresthesias (0.5%) were rare in patients treated with Levadex and comparable to placebo.
Aurora et. al. concluded:
"In this study, MAP0004 was effective and well tolerated for the acute treatment of migraine with or without aura, providing statistically significant pain relief and freedom from photophobia, phonophobia, and nausea in adults with migraine compared with placebo."
Patenting the TEMPO inhaler:
On February 23, 2012, MAP announced that the U.S. Patent and Trademarked office has granted them a patent on the TEMPO inhaler based on their discovery that dihydroergotamine can be "administered to achieve pharmacokinetic profiles that result in rapid efficacy while minimizing side effects that are typically seen with other migraine drugs." The patent will expire in 2028.
Levadex may not be a new medication, but it IS a new method of delivery, one that has the potential to offer relief to Migraineurs who now have problems with current methods of treatment. This inhalation delivery may prove superior for Migraineurs for whom oral medications are ineffective, those for whom nasal sprays are difficult or ineffective, and those who don't like or cannot use injections.
It may not be an answer for Migraineurs who cannot take triptans since ergotamine medications have some of the same warnings as contraindications as triptans, but for some, ergotamine medications are more effective than triptans.
Overall, Levadex will be a welcome addition to the Migraineur's arsenal.
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