Stroke remedy showing promise
SOUTH S.F. FIRM RENOVIS HOPING FOR BLOCKBUSTER DRUG
By Steve Johnson
Mercury News
Dr. Peter Nelson, a Menlo Park physician, felt his left arm and leg suddenly grow weak on New Year's Day 10 years ago. He was having a stroke. Unfortunately, no drug to treat such attacks was available in those days.
Due to the brain damage he suffered, Nelson, then 47, gave up his medical practice, and still has some trouble seeing and concentrating.
``It turned my life upside down,'' he said.
Medicine for stroke hasn't improved much since then. One drug on the market for acute stroke helps only a fraction of patients. And biotechnology companies have run up a remarkable record of failures attempting to make better ones. At least 40 of those drugs, termed neuroprotectants, have flopped in human tests.
But Renovis of South San Francisco finally may have something to offer.
Its treatment -- NXY-059 -- has managed to reduce the disability experienced by some stroke victims, according to data published in February by the New England Journal of Medicine. And while the benefit achieved wasn't earth-shaking, medical experts sound hopeful.
``I'm guardedly optimistic,'' said Dr. Marc Fisher, of the University of Massachusetts Medical School, who has helped set national standards for stroke-drug development. Although he was skeptical of NXY-059 initially, Fisher said, ``In neuroprotection, there is not anything else out there more exciting.''
Renovis Chief Executive Officer and co-founder Corey Goodman, whose company has teamed with London-based AstraZeneca to get NXY-059 on the market, agrees.
``We think it has multibillion-dollar blockbuster potential,'' he said. ``That would be enormous. That would really take us into being a very significant biotech company.''
At least 700,000 Americans suffer strokes each year, one person every 45 seconds. The most common form of the ailment -- ischemic stroke -- occurs when an artery pumping blood and oxygen to the brain gets blocked, usually by a blood clot.
About one-fifth of strokes involve a burst artery in the brain, often caused by an aneurysm, a weak spot in the artery wall. When that happens, blood can spill from the artery into surrounding brain cells.
In either case, the effect can be profound. Patients often suffer a stroke cascade, a chain reaction generating toxic molecules such as free radicals, which can damage nerve cells over much of their brain.
Stroke's high toll
Many victims get dizzy spells and severe headaches, and have trouble speaking, walking and remembering. Others fare worse. Stroke is the third leading cause of death after heart disease and cancer.
The only approved treatment for acute ischemic stroke is tissue plasminogen activator, or TPA, a clot-dissolving agent made by Genentech of South San Francisco. But TPA is given to less than 5 percent of stroke victims.
TPA generally works only up to three hours after a stroke occurs. That's a big problem, because many people don't realize they've had a stroke right away or delay seeking medical care for other reasons.
Help comes too late
``If the stroke onset is at night, there are so many people out there that don't want to bother their doctor at such a time,'' said Nelson, who gives lectures on the dangers of stroke. When they finally do seek help, he added, it's often too late. ``Once you damage brain cells, they really don't repair very well,'' he said.
Moreover, because TPA interferes with the body's ability to stop bleeding, it can worsen the effects of a stroke caused by a burst artery. As a result, patients usually aren't given the drug unless their brains are first checked by a medical test called CAT (computed axial tomography).
As an alternative, drug companies have tried for years to develop neuroprotectants to help shield nerve cells from the effects of stroke, experimenting with everything from anti-inflammatory agents to calcium channel blockers.
These approaches sometimes seemed to have promise in animal tests. But one after another, they failed in people. That is, until Renovis' NXY-059, which is designed to limit the damage free radicals cause nerve cells.
In a test of 1,722 ischemic stroke victims, about 4 percent of those given NXY-059 became completely free of stroke symptoms, according to the New England Journal data. An additional 4 percent could walk without help or were otherwise less dependent on others for their needs.
``Could this be the first neuroprotectant to be successfully translated from animal models and neuron culture to humans?'' asked Dr. Gregory del Zoppo of Scripps Research Institute in La Jolla, in a perspective piece that accompanied the New England Journal study. ``Perhaps.''
Among those who think it could is Dr. Mark Goldberg, who directs an Internet-based stroke educational service for Washington University School of Medicine in St. Louis.
``There are some good reasons to hope that this drug may succeed when others failed,'' Goldberg said. And if NXY-059 proves beneficial in another test under way, he added, ``the impact could be highly significant'' for stroke victims.
Long run of losses
It also could be big for Renovis. Since its incorporation in 2000, the company has had a run of financial losses and as recently as November said it ``expects those losses to continue over the next several years.''
However, that could end with NXY-059, which Renovis acquired in 2002 from a now-defunct Bay Area firm, Centaur Pharmaceuticals. Analysts tracking Renovis are enthusiastic about the drug's prospects and predict the FDA could approve it for sale as early as 2008.
Renovis hasn't disclosed the royalties it would receive from AstraZeneca for potential NXY-059 sales. But Shiv Kapoor, an analyst with investment bank Montgomery & Co., who doesn't own Renovis stock, predicts it would amount to about 15 percent. Based on his estimate that the drug would generate $1.4 billion in annual revenue by 2012, Renovis' share would be $210 million. |
