Migraine treatment innovations still have ways to go

Migraine treatment innovations still have ways to go

Stephanie M. Lee

Published 3:02 pm, Saturday, July 19, 2014

 

Dr. Robert Cowan, head of the Stanford Headache Clinic helps migraine patient Nancy Mikhael, who is getting three rounds of Botox injections as part of her treatment. Photo: Leah Millis, The Chronicle

Dr. Robert Cowan, head of the Stanford Headache Clinic, administers a Botox injection to migraine patient Nancy Mikhael, 31, of San Jose. Photo: Leah Millis, The Chronicle

 

Few sensations are as grating as a head-splitting, nausea-inducing migraine that just won't disappear.

When aspirin and Advil aren't strong enough, patients often turn to the class of drugs called triptans, the prescription medicine DHE or even opioids. But these treatments do not work well in everyone and may have dangerous side effects.

So biotechnology companies, including one in San Mateo, are developing alternatives in an attempt to treat some of the 36 million Americans who suffer migraines. Also on the market are two head devices that use magnets or electricity, one of them developed at facilities in Sunnyvale.

The migraine market in developed countries will grow to nearly $5.4 billion in 2022, predicts the Decision Resources Group. "The unmet need is pretty strong," said Bethany Kiernan, a senior director for the health care market analysis firm. "Having a therapy that can either work to a greater extent in a larger percentage of the population, or that can better serve those patients that are currently underserved, has a real advantage in this market."

Universal relief may be a long way off, however. This month, a panel of California clinicians voiced support for Botox, the wrinkle-smoothing shots that are also approved to treat chronic migraines, defined as severe headaches at least 15 times per month.

At the same time, the doctors were skeptical about the two new head devices.

"These are all promising things, but we still know so little about what's actually going on," said Dr. Robert Cowan, director of Stanford University's Headache Clinic. "How come two different people get hit in the head the same way, one of them gets a lump in the head that goes away in few days or a week, and the other gets chronic headaches that never go away for the rest of their life?"

Seeking cause

Scientists are still trying to understand the exact causes of migraines. Labrys Biologics in San Mateo has been developing a drug that tries to prevent chronic and episodic headaches by binding a protein to a neuropeptide thought to play a role in migraines. In June, Israeli drug giant Teva Pharmaceutical Industries said it would acquire the company for up to $825 million.

But the field has seen some high-profile flops. Last year, Allergan spent nearly $1 billion to acquire a new, inhalable migraine drug, only for the Food and Drug Administration to reject it out of safety concerns.

Allergan also owns Botox. In 2010, the cosmetic injections won approval to treat adults with chronic migraines. Current therapy recommendations call for injections every three months.

Compared to no treatment at all, Botox seems to have small benefits in some patients, the California Technology Assessment Forum agreed this month. The panel of physicians reviews medical issues three times a year.

The group was not as convinced of the merits of SpringTMS, a handheld device that delivers a brief pulse of energy, or transcranial magnetic stimulation, to the back of the head. It is supposed to generate magnetic fields that interrupt abnormal electrical activity associated with migraines.

The device won federal approval in May and is made by eNeura Therapeutics, whose headquarters are in Baltimore and whose research and development facilities are in Sunnyvale. CEO David Rosen said the product may appeal to the estimated 10 to 15 percent of migraine patients who are not eligible for drugs or other treatments.

"It would make sense for a specialist to consider use of the device and prescribe use of the device for patients who don't have any other treatment option," he said. "What are you going to do for these people besides say, 'I don't have a treatment option for you?' "

But the panel decided there was inconclusive evidence to demonstrate the SpringTMS was better than standard treatments. Patients in one study reported some relief after using the device, but other measures, such as whether patients became less sensitive to light and sound, did not significantly differ from the placebo users.

"There really was no difference between the device and a sham stimulator," said Dr. Rita Redberg, a cardiologist at UCSF, who sided with the majority of the panel. It was "just putting something on your head and thinking you were being treated for migraines."

The panel was similarly skeptical of Cefaly, a $449 headband designed to deliver electrical impulses to nerves that transmit migraine pain. Approved in March, it is supposed to be worn for 20 minutes each day to reduce the frequency of migraines - but the panel found the supporting evidence inconclusive.

Few options

At the same time, the group acknowledged that many patients lack viable options. The popular migraine drugs known as triptans, for example, temporarily narrow blood vessels, an effect that makes them off-limits for people with coronary artery disease and other vascular conditions.

Frustrated patients often seek out opioids in the emergency room, but opioids can be dangerous. In a year, the panel estimated, 20,000 patients in California develop chronic migraines because of opioid overuse, and 3,000 become addicted. So the demand for safe and effective alternatives is urgent.

"Headache care is 50 years behind things like diabetes and cancer," said Cowan, the Stanford doctor, who was an adviser to the panel. "It just hasn't had the attention, hasn't had the funding, in order to get to the answers we need."

Stephanie M. Lee is a San Francisco Chronicle staff writer. E-mail: slee@sfchronicle.comTwitter: @stephaniemlee

http://www.sfgate.com/health/article/Migraine-treatment-innovations-still-have-ways-to-5633145.php#photo-6614679

Vagus Nerve Stimulation for the Masses: Interview with electroCore CEO J.P. Errico

Medgadget Exclusive / Neurology

Vagus Nerve Stimulation for the Masses: Interview with electroCore CEO J.P. Errico

by Tom Fowler on May 22, 2014 • 6:05 pm

 

electroCore, a Basking Ridge, New Jersey company co-founded in 2005, is developing non-invasive Vagus Nerve Stimulation (nVNS) therapies which can be delivered using their proprietary gammaCore technology to treat various neurologic, psychiatric, gastric motility, and respiratory conditions. Founded on the pioneering concept of using vagal neuromodulation to acutely treat patients with severe bronchoconstriction during an asthma attack, electroCore has used this concept to expand beyond the acute emergency indications and produce a prophylactic vagus nerve stimulation therapy option. Their initial focus on asthma expanded quickly into migraine and cluster headaches, based on patient feedback from their early studies, and new trials are continuing to investigate new uses for nVNS for gastric motility, pain, and sleep disorders, as well as depression and anxiety. I asked co-founder and CEO J.P. Errico about their gammaCore product, the technology behind it, and his role at electroCore.

Tom Fowler, Medgadget: Tell us how you progressed from being an MIT aeronautical engineering student to a patent attorney to leading a medical device company.

J.P. Errico: I was strongly influenced by my parents, one who was a practicing physician, and the other who had a law degree, to go, professionally, beyond my initial training as an engineer,. So, after graduating from MIT, I went to Duke Law School, where I branched out and simultaneously received a graduate degree in engineering. Because of my focus on patent law, after graduation I was approached by a family member who was a prominent spine surgeon, and within a very short time, our inventive and entrepreneurial bent had us building the first of several healthcare companies. The ventures were largely centered on inventions that could be licensed to market leading companies. The next stage was to begin the clinical development of more innovative technologies, but again these were purchased away from us by the same sort of market leaders. These ventures were successful in generating more than $500 million for our close network of investors. With electroCore, and nVNS, we are committed to building a ground breaking, paradigm-shifting product line. And with recent developments in our clinical and product design programs, I am increasingly confident of our ability to do just that.

Medgadget: How do you foresee gammaCore transforming the standard of care for headache treatment?

J.P. Errico: I foresee physicians, who have as their first obligation to do no harm, offering gammaCore as a first line treatment for their patients. As one of the world leading headache specialist said; “Why would you not use gammaCore first?” I think he is spot on. Through everything we have done, nVNS with gammaCore has been consistently safe, and it is easy for patients to use. Patients can continue with their existing treatments and if it does not work for some of them (nothing works for everyone), they can stop using it. Medications flood the entire body with exogenous chemicals, and thus, invariably have side effects. GammaCore uses the body’s own neural pathways to carry our nVNS therapy, which some refer to as an “electroceutical”, directly to the areas in the brain that release the endogenous chemicals many drug therapies try to modulate. SSRIs, SNRIs, and GABA analogues are some of the largest classes of drugs on the market, and they are designed to alter brain chemistry, and specifically serotonin, GABA, and norepinephrine (also known as noradrenalin). nVNS modulates these same neurotransmitters, but does so without requiring the patient’s liver, kidneys, and other organs to be exposed to foreign chemicals. The other huge benefit, from a patient’s perspective, is that he or she can likely continue with existing medication(s) if they choose, as there have been no observed interactions of nVNS with other treatments, For these reasons and others, electroceuticals is, and will continue to be a rapidly expanding area of healthcare, with GSK starting a new division and investing in multiple bioelectronics companies, and Merck investing in electroCore. I expect many other pharma and medical device companies will follow suit and become involved in this exciting space, and their traditional drugs will, we believe, will slide to the second or third choice… I also believe that patients will demand a non-invasive option that has fewer and more benign side effects than medications as a first option. We expect payors, as well, will appreciate the fact that nVNS can be used both prophylactically and acutely to manage headaches, and with innovative payment options, we hope to make patients and those who hold the purse strings champions of gammaCore.

Medgadget: What is the technology behind gammaCore therapy and are there any risks involved in having patients self administer the nVNS therapy?

J.P. Errico:Vagus Nerve Stimulation was pioneered, twenty-five years ago, by our friends at Cyberonics (Houston, Tx). They were the first to introduce gentle electrical stimulation of the vagus nerve and show that it can selectively stimulate the subset of the nerves in the vagus that have the ability to quiet the surge of activity associated with epileptic seizures. They have recently announced that more than 100,000 patients, world-wide have received their implants, and the profile of safety of their device has been very positive In fact, I believe that the only reason that this therapy option hasn’t climbed the continuum of care from a last resort to front line therapy is the cost and requirement for surgery. GammaCore offers the best of both worlds, the same underlying mechanism of action, without the requirement for surgery and the astronomical cost. In terms of putting it in the hands of patients, I can only say that it takes less time to train a patient to use gammaCore than it takes to train a person to use inhaled medications, and with over 500,000 doses administered to date, we haven’t found any device related adverse events. If the patient doesn’t like it, the therapy can be discontinued in a fraction of a second. In the modern world, we put oxycontin in the hands of patients for headaches, and we feed amphetamines to children with ADHD. Once those pills are ingested, it takes near-heroic efforts to clear those chemicals from the body.

Medgadget: Surgically implanted VNS has been used for some time in the treatment of refractory epilepsy and depression. What is the cost and effect comparison of implants vs. electroCore’s nVNS?

J.P. Errico: Last I heard, Cyberonics was selling their implantable device for over $24,000 in the US. I am not aware of the price point in the EU, or other markets around the world, but of course, that doesn’t include cost of the neurosurgeons’ time, the operating room staff, the anesthesiologist, the long-term maintenance, adjustments, battery replacement, and explanation of the device, if necessary. All of these costs add up to well over $30,000 in the US. Most importantly, VNS doesn’t work for everyone, so the cost for gaining benefits in those for whom it works have to include all the patients in whom it doesn’t (Cyberonics doesn’t give a rebate if the therapy doesn’t work). Reports indicate that 5 years out from the implantation of the device, close to 60% of patients have experienced significant benefit. That means, the real cost for gaining a patient with significant benefit is over $50,000. With gammaCore, while the final pricing of the therapy hasn’t been established, I am very confident to say that we don’t expect payors to commit anywhere near the same amount just to determine in whom the therapy will work. Our goal is to limit the cost of therapy for the payors as closely as can be to just the patients who are gaining the benefit. We are much more like a pharmaceutical in this way, i.e., think of the gammaCore as a bottle of pills containing 300 treatments. When it is used up, it is disposed of and you get another one. Of course, that isn’t quite as socially responsible to the environment – to be tossing things into the garbage all the time – so we intend to introduce reload-able devices that can be refilled with a new prescription, and the fee structure for this would be just like a chronic medication.

Medgadget: You are a named inventor on more than 125 issued US patents, and more than 100 pending patents. What are three tips for those of us that are applying for patents, particularly in the medical device field?

J.P. Errico: This is going to sound corny, but I would say the first thing you want to do is to make sure that whatever it is that you are trying to patent is actually innovative and has potential value to the world. It is an honor to receive a patent, and it is certainly something to be proud of, but they are expensive to obtain, and cost many thousands of dollars to maintain once you’ve gotten them. Make sure it is going to be worth the effort. Second, I would advise people to get an attorney to help. They really do an important service for inventors, and I would NOT suggest to anyone to do it alone. The scope of the patent, and its enforceability are critical to the value they have, so having a professional working with you is critical. Third, and this is specific to the medical field, which is invariably very crowded and intimidating, I would advise anyone with a good idea to commit yourself to your belief. So long as you are not violating the laws of physics, the only thing that stands between you and success is the energy you are willing to expend to make it happen.

Link: electroCore…

 

Tom Fowler

Tom Fowler worked as a programmer in the healthcare IT industry before settling back in school to learn how to become a doctor. He likes to dabble with biotech startups, write postcards to his relatives, and play his ukulele. He was a TEDMED '13 scholar, has published research in biomedical informatics, and continues to advocate for international maternal and child health. Currently in the SELECT MD leadership program at USF Health Morsani College of Medicine.

http://www.medgadget.com/2014/05/vagus-nerve-stimulation-for-the-masses-interview-with-electrocore-ceo-j-p-errico.html

New era for migraine treatment as NICE backs TMS

New era for migraine treatment as NICE backs TMS

World News | January 22, 2014

Selina McKee

 

Six million migraine sufferers living in the UK have today been given a new treatment hope with National Institute for Health and Care Evidence (NICE) backing for a new magnetic pulse procedure.

Following a review of available evidence, which it notes remains limited, NICE’s Interventional Procedures Advisory Committee has concluded that Transcranial Magnetic Stimulation (TMS) - a non-invasive procedure designed to treat or prevent migraine episodes in people with acute or chronic migraine - is safe and effective.

The Institute has not, however, made any recommendations on funding for the procedure, effectively leaving that decision to local clinical commissioning groups, as its interventional procedures guidance only covers the safety of the procedure, whether it works well enough for routine use, and whether any special arrangements are needed for patient consent.

Along these lines, NICE has stressed that doctors should put “special arrangements” in place for clinical governance, patient consent and audit or research if they want to use TMS, which means that they should take "extra care to explain the risks to patients and put in place extra steps to record and review what happens," a spokesperson told PharmaTimes World News.

TMS is administered via a tabletop or handheld device that delivers a predetermined, variable level of magnetic pulse or pulses to the head.

Pain benefit

In one clinical trial data involving 164 patients, those treated for at least one attack of migraine with aura with a handheld sTMS device experienced significantly better pain-free rates two hours after the procedure than those receiving a 'sham' stimulation (39% versus 22%, respectively).

A significantly greater number of patients were also found to be pain-free (with no recurrence and no rescue drug use) at 24 hours (29% vs 16%, respectively) following treatment. 

And on the safety side, no device-related serious adverse events were reported in the trial, NICE noted.

Migraine affects around 10% of adults, but despite the availability of current treatments - such as painkillers, antiemetics, tritons, nerve blocks, Botox and acupuncture - there still remains a significant unmet need for patients.

According to The Migraine Trust, in Britain there are around190,000 migraine attacks every day and 25 million days lost from work or school each year, and it notes that the device may prove particularly appropriate for patients who find other treatments ineffective, or unsuitable, such as during pregnancy.

“This is a breakthrough treatment for those who cannot tolerate or do not respond to current treatment, and opens the door for a new era in treating migraine headaches," noted Consultant neurologist Fayyaz Ahmed, a trustee of The Migraine Trust.

Nevertheless, given the limited amount of long-term safety data available for the procedure, NICE has recognised the need for more research on magnetic stimulation of the brain to prevent and treat migraine.

Read more at: http://www.pharmatimes.com/Article/14-01-22/New_era_for_migraine_treatment_as_NICE_backs_TMS.aspx#ixzz2rIZG8JR9
Follow us: @PharmaTimes on Twitter

FDA Approves First Device to Treat Migraine Pain

FDA Approves First Device to Treat Migraine Pain

Susan Jeffrey

December 13, 2013

The US Food and Drug Administration (FDA) today allowed marketing of the Cerena Transcranial Magnetic Stimulator (TMS; eNeura Therapeutics), the first device approved to relieve pain caused by migraine headache with aura.

"Millions of people suffer from migraines, and this new device represents a new treatment option for some patients," Christy Foreman, director of the Office of Device Evaluation in the FDA's Center for Devices and Radiological Health, said in a statement.

The device is used by prescription after onset of pain associated with migraine with aura. Using both hands, the patient holds the device to the back of the head and, pressing a button, releases a pulse of magnetic energy that stimulates the occipital cortex, stopping or reducing the pain associated with this type of migraine.

"The FDA reviewed the data for the Cerena TMS through the de novo premarket review pathway, a regulatory pathway for some low- to moderate-risk medical devices that are not substantially equivalent to an already legally marketed device," the FDA statement notes.

They reviewed data from a randomized control clinical trial including 201 patients with mostly moderate to severe migraine headaches with auras preceding at least 30% of episodes. Of these patients, 113 recorded treating a migraine at least once when pain was present, and the analysis of these 113 patients was used to support the marketing authorization, the release said.

Results showed that nearly 38% of patients using the TMS device were pain-free 2 hours after using the device vs 17% of control patients. After 24 hours, nearly 34% of treated patients were pain-free vs 10% of the control group.

However, treatment was not associated with relief of other associated symptoms of migraine, including sensitivity to light or sound and nausea, the FDA adds. The device is for use in patients 18 years of age or older, and the study did not evaluate performance of the device in other types of headaches.

Adverse events reported with treatment were rare in both device and control groups, the FDA release said, but included single reports of sinusitis, aphasia, and vertigo. "Dizziness may be associated with the use of the device," the agency adds.

The device should not be used in patients who have metals in the head, neck, or upper body; who have an implanted medical device such as a deep brain stimulator or pacemaker; or those who have suspected or diagnosed epilepsy or a personal or family history of seizures, the FDA statement said.

"The recommended daily usage of the device is not to exceed 1 treatment in 24 hours," it concludes.

http://www.medscape.com/viewarticle/817831

ElectroCore Announces Initial Activities in its Chronic Migraine Prevention and Cluster Headaches Studies Utilizing its GammaCore Therapy

- Company has enrolled first U.S. patients for its FDA approved chronic migraine prophylaxis study

- ElectroCore received FDA approval to begin enrollment of an acute cluster headache study

- Initial enrollment of a cluster headache acute and prophylaxis study has begun in Germany

MORRIS PLAINS, N.J., Jan. 10, 2013 /PRNewswire/ -- ElectroCore®, a company dedicated to developing effective, non-invasive Vagal Nerve Stimulation (nVNS) therapies for serious medical conditions including primary headaches, announced today that initial enrollment has begun for its FDA approved chronic migraine prevention study using its GammaCore nVNS therapy. The randomized, sham-controlled study is enrolling patients at 10 sites across the U.S.

The study, which is expected to offer an initial read out during the first half of this year, will include 60 patients who suffer with migraine more than 15 days per month. Participants will use three 180-second GammaCore treatments per day for two months, comparing the frequency, duration, and severity of their migraines against a control group using a sham device, and against their own baseline data gathered prior to the initiation of the treatment protocol. After the study's initial phases, subjects will be given the opportunity to continue using the prophylactic therapy for six additional months.

"GammaCore is the first non-invasive device capable of stimulating the cervical branches of the vagus nerve, enabling self-administration of therapy without a surgical procedure," said JP Errico, CEO of ElectroCore. "Positive results from this study will bring us one step closer to providing an important new treatment option to the more than seven million Americans who suffer from chronic migraine."

Additional ElectroCore activities include:

• Initial enrollment has begun in a randomized cluster headache study being conducted by leading neurologists at six sites in Germany with the intent of establishing government reimbursement for nVNS therapy. In the first phases of the study, 90 chronic cluster headache patients are being randomized between GammaCore nVNS therapy and the standard of care. After the first four-week phase, all patients enrolled in the study will be provided GammaCore nVNS therapy during a final phase. In this study, the therapy will be used as both an acute and a prophylactic treatment of their condition. GammaCore nVNS therapy has already been CE marked, and is commercially available in Germany and across the European Union.
  
• ElectroCore received FDA approval to begin a pivotal study of GammaCore as an acute treatment for cluster headaches. This trial, expected to begin enrolling during the first quarter of 2013, will study the acute benefits of treatment of cluster headache events in 150 chronically suffering subjects at 15 sites across the U.S. During the initial phase of the study, subjects will be randomized against a sham device for a period when they will treat up to five headache events in a two-week period. At the conclusion of the first phase, all 150 subjects will be provided access to the GammaCore nVNS therapy for a period of six months. This study is expected to read out with an interim analysis in the first half of this year. Based on the results of the study, ElectroCore plans to submit for U.S. Food & Drug Administration approval of GammaCore for the acute treatment of cluster headaches.
  
• GammaCore technology was featured in a poster session at the 2012 European Headache and Migraine Trust International Congress in London. Fourteen patients attending headache centers in the U.K. and Ireland were offered non-invasive VNS treatment and questioned during routine follow up about their experience with the device and the perceived impact. Thirteen felt there was an overall improvement in their condition since using the device (the median device use period was 13 weeks), suggesting that GammaCore appears to be well-tolerated and effective in both the acute and preventive treatment of episodic and chronic cluster headache.

About ElectroCore®ElectroCore is a healthcare company focused on non-invasive neuromodulation therapies for the treatment of diseases and disorders. The company has developed non-invasive Vagal Nerve Simulation (nVNS) therapies intended to treat and/or prevent symptoms of a number of highly prevalent and disabling conditions. ElectroCore currently has three commercial products on the market: GammaCore®, AlphaCore®, and GammaCore VET™. The company is headquartered in Morris Plains, NJ, with international offices in Stockholm, Sweden, Hamilton, Bermuda, and Sydney, Australia.
For more information, visit: http://www.electrocoremedical.com/.

SOURCE ElectroCore Medical

http://www.prnewswire.com/news-releases/electrocore-announces-initial-activities-in-its-chronic-migraine-prevention-and-cluster-headaches-studies-utilizing-its-gammacore-therapy-186303961.html