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Gene Therapy Takes a Turn for the Better


Recent successes are giving drugmakers and patients hope

"People were fed up with big promises and not seeing results"

Jean Erickson, a former preschool director, suffers from Parkinson's disease. Her mobility was improved when doctors drilled a hole into her skull and injected a cold virus modified to help transport a gene into her brain.

The gene created a mini-factory within her cells to pump out dopamine, a chemical that regulates physical movement. "I stopped freezing up," says Erickson, whose treatment was part of research funded by Genzyme (GENZ).

Successes like Erickson's are leading to a revival of interest in gene therapy, which had pretty much dropped off the medical map after the death 11 years ago of an 18-year-old patient. Genzyme and Pfizer (PFE) in the U.S. and Novartis (NVS) in Europe are leading the pack. There are currently 354 U.S. studies under way employing gene manipulation. That's up from 116 worldwide in 2008. San Jose (Calif.) researcher Global Industry Analysts forecasts that sales of gene-based therapies could exceed $465 million annually by the year 2015.

Recent advances in treating brain and eye disorders—and improvements in safety during trials—have led some researchers and investors to compare the current state of play in gene therapy to the early days of biotech: "There were lots of ups and downs, lots of believers and nonbelievers," says Nick Leschly, a partner in Third Rock Ventures, a lead investor in a $35 million round of financing for Genetix, a Cambridge (Mass.) startup. But "look at Roche's Genentech (DNA) portfolio today: Avastin, Rituxan, and Herceptin. Right there, you've got $17 billion in sales. That's the kind of future we see for gene therapy over time."

For drugmakers, the goal is to move gene therapy beyond advances against relatively small "above the neck" disorders toward mainstream illnesses, such as Alzheimer's, hypertension, and diabetes, that affect millions of patients globally. That's where Big Pharma makes its big money. "Now the real challenge is to choose the right targets, which diseases and, from a commercial point of view, which markets make sense," says Ronald Crystal, a researcher at Weill Cornell Medical College in New York who helped pioneer the field two decades ago.

Genes contain instructions for cells to make proteins that carry out chemical reactions in the body and help the immune system fight infections. When a gene is defective and can't make the correct protein, disease can occur. While conventional drugs use natural substances or chemicals to fight illness, gene therapy treats disease by replacing malfunctioning genes with healthy ones.

It was first used in the 1990s to treat 19 children with the so-called Bubble Boy disease, in which the immune system is unable to fight germs. While the children were saved, five later developed leukemia. A more devastating failure occurred in 1999 when 18-year-old Jesse Gelsinger died of a massive immune response within hours of being treated for liver disease. "Gene therapy was dead as a doornail," says Axel Polack, a general partner at TVM Capital, a venture capital firm. "No one was investing anymore. People were fed up with big promises and not seeing any results."

In recent trials, a different type of cold virus, which triggers milder immune responses, is being used to transmit genes into patients. That has helped fuel renewed interest in the therapy. Genzyme has invested "well north" of $200 million in gene therapy research over the past 10 years and now has more than 80 employees working on the technology, says Sam Wadsworth, a Genzyme group vice-president.

Other large drug companies are cementing partnerships. In January, Novartis licensed gene treatments for hearing loss and balance disorders from Maryland-based GenVec (GNVC), in a deal worth up to $213 million. A month later, startup Tacere Therapeutics announced that Pfizer would license its hepatitis C treatment in an agreement valued at as much as $145 million.

Only China has approved gene therapies for actual medical use, for two types of cancers. The first U.S. approvals will come in about four years, predicts Philip Reilly, chief medical officer at Genetix, which hopes to market a French gene treatment to stop a rare form of progressive brain damage. Genzyme is launching larger trials of genetic treatments for Parkinson's and a form of macular degeneration that causes severe vision loss in 1.4 million Americans over age 40. The payoffs could be substantial: The market for Parkinson's drugs alone reached $3.6 billion in 2008.

Still, gene therapy is unlikely to produce revenue for Genzyme or any company for several years, says Cowen & Co. analyst Phil Nadeau. "Over the long haul it's very intriguing and holds a lot of promise, particularly for some of the rare disorders," he says. "But there have been a lot of fits and starts and, from a public-market investment standpoint, it's still too early."

Not for 9-year-old Corey Haas of Hadley, N.Y. Since the 2008 gene therapy trial that gave him clearer vision in one eye, Haas says he can ride his bike and recognize colors. Now he wants doctors to go to work on his other eye. This year, he says, "I'm going into Little League."

The bottom line: Researchers and investors are heartened by advances in gene therapy. Analysts say revenues are still several years off, however.


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