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Stopping Migraines Before They Hurt: NeurAxon Pursues New Pain Drug

Xconomy Boston — 

Nobody has yet come up with a drug that can stop the pain from migraine headaches before it starts. By this time next year, the people at Waltham, MA-based NeurAxon will know if they have created the first drug that works for the roughly one-third of patients who get a serious inkling before migraines kick in that pain’s on the way.

This company first grabbed our attention in August 2007, when it raised $32 million in venture capital from leading healthcare investors, including Delphi Ventures and OrbiMed Advisers. I got an update about the company’s aggressive game plan a couple weeks ago from CEO Lawrence Bloch at an investor conference in San Francisco.

Migraine headaches affect about 30 million people in the U.S., so any powerful new drug aimed at helping this group has a big opportunity. NeurAxon’s lead pill in development is designed to combine the pain relief of a standard drug from the family of “triptans,” along with the more novel ability to inhibit another enzyme called nNOS that controls pain sensations. Blocking this particular enzyme is important because no other pain drug specifically hits it, and the target is associated with what is known as “aura.” These are the flashes of light in people’s vision, the zigzagging patterns, or blind spots that about one-third of migraine sufferers get about 30 to 90 minutes before pain sets in. Early clinical trials suggest that NeurAxon’s drug might be the first that patients could take when the “aura” comes on, which means the drug could start working in time to fight the pain before it starts.

“If we can prove that we can dose at aura, it’s a fundamental breakthrough,” Bloch says. “There’s never been a drug like that.”

The current state-of-the-art “triptan” family of seven drugs generates about $3 billion a year in worldwide sales, Bloch says. The leader of the class is GlaxoSmithKline’s sumatriptan (Imitrex), which is scheduled to face competition from cheaper generic copies next year. (Although Glaxo may have protected its market a while longer with a new combo of sumatriptan with the pain reliever naproxen, called Treximet, that won FDA approval in August). Drugs in this class are not a panacea, because they have to be taken once a patient already feels migraine pain, and then they offer some relief for 50-75 percent of patients within two hours. They don’t last a full 24 hours, allowing room for so-called “rebound” headaches. The drugs also come with a warning that they can cause high blood pressure and other heart side effects like stroke.

NeurAxon, which got started in 2004, has built its secret sauce around compounds designed to last longer in the body, and be more effective by specifically hitting that extra neuronal nitric oxide synthase (nNOS) enzyme. Scientists have long known the enzyme is intimately related to pain sensations, but the target has stymied drug developers because it is so structurally similar to other families of enzymes. If you hit too many of the related enzymes, it can lead to damaging heart effects, Bloch says.

The company has completed a clinical trial in 192 patients has shown that NeurAxon isn’t causing dangerous heart affects at any dose tested, Bloch says. Now it’s time for the tougher exam. Does it work any better, is it really safe for the heart in repeated studies, and does the pain relief last long enough?

This is a pivotal year for answering those questions. NeurAxon has lined up three mid-stage clinical trials. The first will enroll about 150 to 200 migraine patients, including those with and without the “aura.” Those patients will have to wait until their pain starts to take the NeurAxon drug, or a standard “triptan.” The goal will be to see whether the experimental drug is better at causing pain relief after two hours, and whether it’s sustained for a full 24 hours.

The second trial will enroll 30 to 40 migraine patients with “aura,” and will give them the drug the instant that visual cue shows up, to see whether it can prevent them from feeling migraine pain. The next time patients have an “aura” come on, they will be given a placebo to see just how much better the drug really is.

A third trial is for a pain condition you don’t hear nearly as much about—painful bladder syndrome (aka interstitial cystitis). Interestingly, NeurAxon is bullish about this study because its compound has been designed to last 24 hours in the body before it is excreted entirely through urine. That means the pain drug naturally funnels through the bladder, which happens to be a problematic, painful organ for about 1.3 million people in the U.S., mostly women—so it’s possible the drug will represent a new, more direct way to treat this condition. This trial will also have about 150 to 200 patients, Bloch says.

This game plan all sounds really expensive, and NeurAxon is doing all of it without a partner. Apparently, the company has stretched its cash reserves a long way. NeurAxon should have enough money until August 2010, and hopes to have positive clinical trial results in hand before then, in the first quarter of 2010, Bloch says. Once the proof of effectiveness in clinical trials is established, then it will be time to cut a deal with a Big Pharma company to take it the rest of the way through the pivotal clinical trials needed to pass muster with the FDA, he says.

If NeurAxon can reach its goals, one of the very first customers will be its chief medical officer, Robert Medve, a chronic migraine sufferer himself. There are almost too many scenarios to sketch out at this point, but if NeurAxon can show that its drug has even a similar effectiveness profile to what’s already on the market, yet lasts longer and avoids the heart affects, it will be a winner, Bloch says. “Our chief medical officer would raise his hand and say ‘I want that drug,'” Bloch says.