Several new formulations and delivery systems for acute migraine medications have been developed and are in clinical trials or awaiting approval.
STOWE, VT—Novel drug delivery systems and potential targets for migraine therapy were among the recent developments reported at the Headache Cooperative of New England’s 21st Annual Headache Symposium.
Alan Rapoport, MD, Clinical Professor of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, reviewed the calcitonin gene-related peptide (CGRP) antagonists, nonsteroidal anti-inflammatory drugs (NSAIDs), and triptans already approved for migraine treatment. He also discussed general principles for migraine treatment, as well as emerging therapies and off-label uses for approved medications and devices.
“Proper treatment begins with an accurate diagnosis,” said Dr. Rapoport, who is also the Founder and Director-Emeritus of the New England Center for Headache in Stamford, Connecticut, and the President-Elect of the International Headache Society. “The right way to treat patients is to treat them correctly the first time. If the patient has migraine, we should treat him or her with a migraine-specific treatment right up front and not fool around with other medications.”
“Triptans Are the Standard of Care”
Early intervention—administering a triptan at the first sign of headache—is key to treating migraine acutely. “Teach the patient to give it early or when the pain is mild, and certainly within 20 minutes to prevent central sensitization,” Dr. Rapoport advised.
“Injection of triptans is probably the fastest way to get a patient better,” he said. However, he also warned that delivering medication so quickly into a patient’s system carries an increased risk for adverse events.
“If treatment isn’t working, you have to try to figure out why, and it’s often that you have to change the dose of the drug,” noted Dr. Rapoport. “If a patient is nauseated or vomiting, or he or she is just not absorbing the drug well by mouth, it may be very important to change to a nasal spray, injection, or other routes of administration.”
New Sumatriptan and DHE Delivery Systems
“Everything old is coming back,” Dr. Rapoport said of the new formulations of and devices designed for existing medications. “[Dihydroergotamine (DHE)] is coming back; sumatriptan is coming back in different ways.”
One of the new DHE delivery systems is a novel, breath-actuated inhaler called Levadex (MAP Pharmaceuticals, Inc; Mountain View, California) designed to deliver the majority of the drug deep into the lungs while minimizing oropharyngeal deposition. “It’s a brand new type of device that will have DHE suspended in hydrofluoroalkane propellants,” Dr. Rapoport explained. “I like DHE because it can be used acutely, it can be used late when the patient has already developed central sensitization and allodynia, and yet there’s very little nausea and vomiting [with this delivery system].... Most importantly, it can be used at home.”
OptiNose (OptiNose US, Inc; Yardley, Pennsylvania), a bidirectional breath-powered device used to deliver a sumatriptan powder, is another novel route of administration designed to deliver medications more effectively than current technologies. “It not only coats the bottom of the nose where the nasal sprays did, it coats the entire nasal cavity bilaterally, so there’s much better absorption,” commented Dr. Rapoport. The device is still in trials, but “the phase II data look promising and I think [the developers are] actually going to make some inroads if they get this device approved.”
The NP101 patch known as Zelrix (NuPathe Inc; Conshohocken, Pennsylvania) is another novel sumatriptan delivery system. The transdermal patch uses low levels of electric current to drive approximately 6 mg of sumatriptan through the skin over time. “The adverse events from these trials were localized sensations at the patch site,” Dr. Rapoport reported. “It’s very exciting that you can give a triptan that doesn’t cause any triptan adverse events…. If a person is having trouble with nausea, vomiting, or isn’t doing well with oral triptans, this is a very good alternative.”
Glial Modulators and Other Potential Treatment Targets
The glial activator AV411 (Avigen, Inc; Alameda, California) has ibudilast as its active ingredient and “looks like an incredible type of new medication,” according to Dr. Rapoport. “It’s only in phase II trials, but it does everything you’d want it to do,” he continued. “It suppresses the production of proinflammatory cytokines, like interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6, while enhancing the production of anti-inflammatory cytokine interleukin-10.” Ibudilast is also believed to up-regulate the release of neurotrophic factors and suppress neuropathic pain. “We know now that the glial cells are extremely important, and it looks like we’re going to be able to affect them,” said Dr. Rapoport.
COL-144 (CoLucid Pharmaceuticals, Inc; Research Triangle Park, North Carolina), a 5-HT1F agonist in IV form that contains lasmiditan, is undergoing investigation and has been shown to result in significant pain relief and freedom without any significant adverse events. In addition, according to Dr. Rapoport, “early stage research is being done on large conductance, calcium-activated potassium channels, and we look forward to learning more about this.”
Dr. Rapoport concluded with an overview of general principles for the acute treatment of patients with migraine. “Triptans or faster-acting NSAIDs, such as diclofenac potassium for oral solution (Cambia; Nautilus Neurosciences, Inc; Bedminster, New Jersey), should be our first choice until a DHE inhaler (such as Levadex) is available. These should all be given early in the course of the headache unless there’s any kind of contraindication,” he stated. “We’ve got a lot of good medications coming, so we’ve got so much to look forward to.”