STOWE, VERMONT—Headache therapies of the near future will include new delivery routes for established medications, as well as comparatively new nerve-stimulation techniques, according to an overview presented at the 23rd Annual Winter Headache Symposium of the Headache Cooperative of New England.
Merck, Bristol-Myers Squibb, and other companies have developed drugs that block the receptor for calcitonin gene-related peptide (CGRP) for the acute treatment of migraine, said Alan M. Rapoport, MD, Clinical Professor of Neurology at the University of California, Los Angeles. Although Merck’s drug telcagepant and a follow-on compound showed promise, the company discontinued development of both because of liver toxicity. Other companies appear to be developing similar drugs, however, said Dr. Rapoport.
In addition, Amgen is developing an antibody to the CGRP receptor, and Alder Biopharmaceuticals, Arteaus Therapeutics, and Labrys Biologics are developing antibodies for CGRP itself. Labrys is the only company that is developing its antibody for chronic migraine. The drugs are still in early development, and studies have not revealed any toxicity so far, said Dr. Rapoport.
New Delivery Methods for Sumatriptan and DHE
A small device created by OptiNose coats both nostrils with sumatriptan powder when the patient blows into one end. In its first phase II trial, about 80% of patients using the device had pain relief at two hours, compared with 42% of patients using placebo. A subsequent study gave further evidence of efficacy, and OptiNose will seek device approval during the next few years, said Dr. Rapoport.
NuPathe recently received FDA approval for its iontophoretic sumatriptan patch called Zecuity. The battery-powered patch uses electricity to send the drug through the skin for the acute treatment of migraine. The patch’s pharmacokinetic curve was designed to avoid triggering adverse events associated with triptans. Approximately 18% of patients using Zecuity were pain-free at two hours, compared with 9% of patients who used placebo. About 34% of patients using Zecuity had sustained pain relief (ie, two to 24 hours), compared with 21% of patients using placebo.
Sumavel DosePro, manufactured by Zogenix, enables patients to self-inject sumatriptan in the abdomen or leg without a needle. A patient takes the top off of the device, flips a lever, and presses the device to the skin to administer the injection. “Patients tend to like it.… It’s also safer to use, because you don’t have to worry about the disposal of sharps,” said Dr. Rapoport. Another device, Pfizer’s Alsuma, is similar to the EpiPen and delivers sumatriptan using a needle.
Dihydroergotamine (DHE) may soon be available as Levadex, a breath-actuated inhaler developed by MAP and now owned and manufactured by Allergan. Phase II studies showed similarities between the efficacy of Levadex and that of IV DHE, but the inhaler’s pharmacokinetic curve prevents most of the nausea and vomiting associated with IV DHE, said Dr. Rapoport. Approximately 59% of patients using Levadex had pain relief at two hours, compared with 35% of patients using placebo. About 44% of patients using Levadex had sustained pain relief, compared with 20% of patients using placebo. “This will be easy to use at home,” said Dr. Rapoport. The FDA may make a final decision about the treatment before the end of the year.
New Treatments for Cluster Headache
Two emerging devices treat cluster headache through nerve stimulation. Autonomic Technologies has created a small electrode for implantation on the sphenopalatine ganglion in a minor procedure under general anesthesia that lasts about 30 minutes. The patient controls the electrode, which is not connected to any wires or batteries, through a remote control stimulator placed over the cheek. The pain of 67% of cluster attacks treated with stimulation was relieved at 15 minutes, compared with 7% of attacks treated with sham stimulation. Also, 64% of patients had improvement in headache disability, and 75% had improvement in quality of life. Early data indicate that the device may decrease the frequency of attacks. The company finished its European study of the device for chronic cluster headache and started a multicenter, randomized study in Europe to evaluate the apparatus for frequent, disabling, unilateral migraine, said Dr. Rapoport.
In addition, ElectroCore has created the GammaCore device for noninvasive vagal nerve stimulation. Peter Goadsby, MD, PhD, Professor of Neurology at the University of California in San Francisco, studied the device in an uncontrolled, unblinded trial. “He said patients like it, and they seem to be getting better,” noted Dr. Rapoport. Early data appear promising. ElectroCore has begun trials of the device, which appears to be safe, in the United States and other countries. If the GammaCore method proves effective at relieving cluster headache, it “could be successful very quickly, as it appears to be extremely safe,” concluded Dr. Rapoport.