Migraine Patients to Wait for Triptan Alternative

Scandinavian researchers writing in The Lancet gave a warm review to an investigational drug for migraine, but patients in the United States, at least, will have a wait before it reaches them.

Merck manufactures the drug, called telcagepant, and was initially expected to seek approval from the U.S. Food and Drug Administration last year.

An online Lancet review by researchers from Sweden and Norway touted telcagepant as holding out hope for migraine patients with acute attacks that fail to respond to migraine medications known as triptan drugs, such as Zomig and Imitrex. One major concern of these drugs has been their tendency to cause narrowing of the blood vessels, a process known as vasoconstriction.

"Telcagepant does not cause vasoconstriction, a major limitation in the use of triptans," wrote Dr. Lars Edvinsson of University Hospital in Lund, Sweden, and Dr. Mattias Linde of Norwegian University of Science and Technology in Trondheim.

"Telcagepant might provide hope for those who have a poor response to, or are unable to use, older drugs."

But elevations in certain liver enzymes among some telcagepant trial participants caused Merck to hold back in the U.S., fearing an application would be rejected. In September, the company announced that it was meeting with FDA officials to discuss how to proceed.

As a result, a Merck spokeswoman told MedPage Today, the company will sponsor another clinical safety study to begin this year. She said the trial was still being designed, and the protocol would be posted to the Clinicaltrials.gov Web site about the time enrollment begins.

No other information, such as the projected completion date, is available at this time, the spokeswoman said.

The group of drugs called CGRP receptor antagonists, to which telcagepant belongs, represents a new front in the war on migraine, as Edvinsson and Linde explained.

The receptor appears throughout the nervous system, both central and peripheral, and researchers believe it helps regulate vascular tone, pain signaling, motor function, and other activities with neurologic components.

A variety of studies have implicated it specifically in migraine, notably findings that CGRP levels rise in cranial blood and saliva during attacks.

But the two researchers said the clinical findings with telcagepant were marred by the liver abnormalities, which they called "slightly disturbing."

A 12-week phase IIa trial was stopped a year ago when some patients showed these liver problems toward the end of the study.

Edvinsson and Linde also noted that relatively high doses of the drug are needed to reduce migraines -- more than 100 mg, compared with 5 mg for zolmitriptan.

"Outstanding questions include whether CGRP receptor antagonists can be combined with triptans to give more effective therapy and whether they will be of value in patients who do not respond to a triptan," the researchers wrote.

"Additionally, effectiveness of triptans in children has not been proven, a group that might benefit after such research."

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NuPathe ready with new drug application for migraine treatment

NuPathe Inc., the Conshohocken specialty pharmaceutical company that is getting ready to file a new drug application for its experimental migraine headache treatment, has expanded its partnership formed in 2007 to take on Parkinson’s disease.

Late Monday, NuPathe entered into a license agreement for drug-delivery technology with SurModics Inc., a publicly traded Minnesota life sciences company.

The companies began a collaboration in 2007 aimed a developing a biodegradable sustained-release formulation of an approved dopamine agonist.

The partnership has yielded NuPathe's NP201, which it described as “the first long-acting treatment available in broadly acceptable dose form that maintains the potential to provide sustained relief from Parkinson's disease without motor response complications.”

The experimental product combines NuPathe's long-acting delivery technology and SurModics' proprietary biodegradable polymer matrix implant technology.

Under the licensing agreement, NuPathe will lead and fund development and commercialization. SurModics will provide technical and manufacturing expertise and will be eligible to receive licensing fees and milestone payments related to development of products for the treatment of Parkinson's disease and other clinical indications. SurModics will also receive royalties on product sales.

Other financial details were not disclosed.

Parkinson's disease, a brain disorder, occurs when certain nerve cells in the substantia nigra portion of the brain die or become impaired. Normally, these cells produce a vital chemical known as dopamine. Dopamine allows smooth, coordinated function of the body's muscles and movement.

About 1.4 million people suffer from Parkinson's disease in the United States, Europe, and Japan. By 2050, this number is expected to double.

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New Migraine Drug Shows Promise

An experimental inhaled drug called Levadex is an effective treatment for migraines, according to a drug company-funded study.

The phase III trial, conducted at the Jefferson Headache Center at Thomas Jefferson University Hospital in Philadelphia, found that migraine patients who took the drug had greater relief from symptoms such as pain, nausea and light/sound sensitivity than those who took a placebo.

The drug provided pain relief within 30 minutes and sustained relief for 48 hours in patients with moderate or severe migraines. There were no drug-related, serious adverse effects, according to a news release issued by the university.

"The major advantage of Levadex is that it has the efficacy of intravenous DHE (dihydroergotamine) with a side-effect profile similar to placebo and better than oral triptans," Dr. Stephen Silberstein, director of the Jefferson Headache Center, and professor in the neurology department at Jefferson Medical College, said in the news release.

The study was funded by MAP Pharmaceuticals, Inc. Silberstein serves on the advisory board of the company.

Source : health.usnews.com

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New developments for migraine treatment

Migraines are experienced by millions of individuals and constitute a significant impairment for those who are affected. In many cases, migraines are severe enough that they may be considered a disabling impairment.

Migraines are the most common form of reoccurring and persistent headache, estimated to affect 15% of the population and three times as many women than men.

Yet many do not seek professional medical care for their migraines, and it is estimated that doctors overlook the condition in as many as half of those who seek help.

Migraines are usually characterized by throbbing pain on one side of the head, and can last for as long as 72 hours. They can include nausea, vomiting, difficulty with movement, and sensitivity to light and sound. They are linked to hormonal changes and seem to be hereditary. Triggers include weather changes, not sleeping enough or over-sleeping, missing meals, and drinking alcohol.

The World Health Organization even considers the most severe migraines as debilitating as being psychotic or quadriplegic. Most patients take basic over-the-counter non-steroidal pain medications and anti-inflammatories such as ibuprofen or aspirin to treat the symptoms after the onset of a migraine.

Being in a quiet, dark room also seems to help subside a migraine attack. But these tactics do not prevent migraines and often have limited effectiveness in ending an attack, especially for those who suffer more severe migraines.

There are more powerful prescription medications that are more effective at treating migraines - but only in about half of all patients. Triptans can be taken after a migraine begins to alter brain chemistry and ease the symptoms. Other medications are available to help prevent the occurrence of migraines.

Very few people are actually on these medications, in part because they have a high risk of negative side effects. Topiramate, a new preventative medication, causes cognitive problems in one out of five patients. Plus, triptans and similar drugs work by constricting blood vessels, which raises the risk of heart attack and stroke, particularly in patients who are vulnerable to these conditions.

There is hope, however, as new preventative medications are in development. These are gap junction blockers, altering brain chemistry at points where nerve cells interact. It seems these medications may limit overactive nerve cells thought to cause migraines. New treatment drugs are also in development. These block a brain chemical that has higher levels in those with migraines. Trial results show fewer side effects and better success rates than drugs currently on the market. It seems the future of drug treatments is bright for migraine sufferers.

by : Tim Moore
Source : www.articlesfactory.com

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New Therapy For Migraine

A new UCSF study examining the mechanism of a novel therapy that uses magnetic pulses to treat chronic migraine sufferers showed the treatment to be a promising alternative to medication.

The therapy is called transcranial magnetic stimulation, or TMS. Study findings were presented April 29, 2009 during the annual American Academy of Neurology scientific meeting in Seattle.

In a previous randomized controlled clinical study by Ohio State University Medical Center, TMS was used to treat patients who suffer from migraine with aura, a condition in which a variety of mostly visual sensations come before or accompany the pain of a migraine attack. The study showed that TMS treatment was superior to the placebo given to the control group. Patients were pain-free at follow-up intervals of 2, 24 and 48 hours.

In the new study, conducted in rats, UCSF researchers focused on understanding the mechanism of action of TMS therapy -- how the treatment interacted with the brain to produce the pain-free outcomes of patients in the previous study.

The UCSF research identified potential opportunities to enhance treatment strategies in patients. One example, the study team noted, was that factors such as time and peak intensity of stimulation may be important components in the brain's response to TMS.

"The data demonstrate a biological rationale for the use of TMS to treat migraine aura," said Peter Goadsby, MD, PhD, lead investigator of the study, professor and director of the UCSF Headache Center. "We found that cortical spreading depression, known as CSD and the animal correlate of migraine aura, was susceptible to TMS therapy, with the wave of neuronal excitation blocked on over 50 percent of occasions."

The study findings showed that migraine aura responds to magnetic stimulation because TMS therapy blocks the wave of neuronal excitation, which is a biological system through which neurons become stimulated to fire. TMS creates a focused magnetic pulse that passes noninvasively through the skull, inducing an electric current to disrupt the abnormal brain waves believed to be associated with migraine, including CSD. CSD in humans precedes migraine with aura.

The American Academy of Neurology estimates that over 30 million Americans suffer from migraine, a syndrome characterized by recurrent, often excruciating headaches. The National Headache Foundation estimates that migraine causes 157 million lost workdays each year due to pain and associated migraine symptoms, resulting in a $13 billion burden to American employers.

Further research is needed, the UCSF team said, but the findings give neurologists a potential new treatment option for migraine sufferers unable to tolerate medication, which can cause stomach bleeding and other painful side effects.

Additional study investigators were Philip R. Holland, PhD, UCSF; Carol T. Schembri and Joe P. Fredrick, Neuralieve, Sunnyvale, Calif.

The research was funded by Neuralieve, Inc., of Sunnyvale, Calif., which provided the TMS technology for the study. Goadsby has served as an advisor to Neuralieve for which he received an honorarium.

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Merck Suffers Blow Developing New Migraine Drug

Merck, maker of the Maxalt migraine drug, has been betting heavily on adding a new medicine to its lineup aimed at the multibillion-dollar migraine market. The company has been planning to ask the FDA this year to approve the medicine, telcagepant, and analysts predicted the drug could have $800 million or more in sales in 2015. Analysts considered telcagepant one of Merck’s key new products.

But the drug maker announced this morning that it would delay taking telcagepant to the FDA, and one analyst wondered whether the drug would ever make it. “It is fully conceivable that this product will be terminated,” Sanford Bernstein’s Tim Anderson wrote in a note to investors.

The problem: some patients participating in an exploratory study gauging whether the drug could be taken daily to prevent migraines developed high levels of liver enzymes. The company stopped the study and is reviewing data from another study, said Peter Kim, Merck’s research chief. Meantime, it is moving ahead with studies of the drug’s intermittent use to treat migraine attacks.

Merck disclosed the telcagepant news in announcing disappointing financial results for the first quarter.

The struggles are another reminder of the unpredictability of drug research and development, and the difficulties that Merck and other big pharmaceutical companies have had finding lucrative new drugs to replace the blockbusters losing patent protection over the next several years.

More than a third of Merck’s revenues come from drugs whose patents run out through 2013, according to Edward Jones’ Linda Bannister. The depth of its “patent cliff” is so steep that Merck, which had prided itself on its homegrown research, is now inking drug development deals with outside firms. More telling, it agreed to buy Schering-Plough for $41.1 billion.

Seamus Fernandez, a Leerink Swann analyst, told the Healh Blog that the telcagepant news — combined with its poor first-quarter performance — “increases the importance of a successful merger outcome.” In a conference call with analysts, Merck officials said the merger, slated for completion in the fourth quarter, was on track.

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