Staff Writer

The American Society of Gene Therapy's annual meeting last week in San Diego offered an impressive array of clinical data demonstrating just how far the field has come.

Too bad no one from the drug industry was on hand to see it.

And therein lies one of gene therapy's greatest challenges: The field is finally starting to realize some of its enormous potential . . . but pharma and biotech companies are not particularly interested in picking up the tab.

"Like any other field, the big issue right now is funding," said ASGT President David Bodine, noting that almost all gene therapy trials are grant-funded. "If there was VC or pharma interest, things would go faster. Not necessarily better, but faster."

The one sector of gene therapy with some industry interest - and thus with the most progress to date - is cancer.

Introgen Therapeutics Inc.'s gene therapy Advexin for head and neck cancer almost gained the field's first FDA approval last year - but a Phase III trial failed, the agency refused to file Introgen's biologics license application, and the company filed for Chapter 11 bankruptcy protection.

Despite Introgen's implosion, John Nemunaitis, oncologist and medical director of the Mary Crowley Medical Research Center, believes Advexin works when given to the right patients. He presented data at ASGT showing significantly improved survival in a subset of patients with a favorable p53 biomarker mutation analysis.

Even so, Introgen's outcome did not inspire confidence in the field, and a suitor has yet to rescue Advexin. Even gene therapy companies with good late-stage cancer data and no major mishaps to speak of can't find partners.

BioVex Inc. has been trying since 2003 to snare a U.S. partner for OncoVEX, a modified herpes simplex virus delivering the gene for gmCSF. The product is in Phase III for melanoma, and Phase II data presented at ASGT showed median survival of 16 months - but no one has signed on the dotted line.

GenVec Inc., too, has been unable to find a partner despite advancing into a Phase III pancreatic cancer trial with TNFerade, an adenovector containing tumor necrosis factor-alpha.

The Reality of Perception

Debjit Chattopadhyay, analyst with Boenning & Scattergood Inc., attributed the lack of partnering interest to the fact that deaths have derailed some gene therapy clinical trials. Even though a decade has passed since the high-profile death of young gene therapy patient Jesse Gelsinger, and some subsequent deaths were ultimately attributed to non-treatment-related causes, Chattopadhyay said there remains a "perception" of safety problems.

"Gene therapy needs a Dendreon," Chattopadhyay said, referring to the fact that no one believed in therapeutic cancer vaccines until Dendreon Corp.'s recent Phase III success with Provenge (sipuleucel-T) in prostate cancer, which boosted the entire field.

While some biotechs are willing to bet on cancer, gene therapy has shown the most potential - and received the least industry interest - in rare genetic diseases.

At ASGT, scientists presented data from clinical trials using gene therapy to correct inherited blindness: Patients went from barely being able to see a hand waving in front of their face to reading three or four lines on an eye chart. Another study of gene therapy for ADA-SCID (a.k.a. bubble boy disease) had all 15 patients alive and well - without bubbles - as much as eight years after treatment.

Who Really Wants a Cure?

Yet several scientists at the conference claimed that industry is not interested in curing diseases with a single treatment - they grumbled that companies would rather see patients on a drug that requires a lifetime of administration.

Chattopadhyay said that's taking it a bit far - gene therapy isn't really at the point where it can claim to be a cure. "But there is some truth to that," he mused. After all, is a car company going to sell you a car that lasts forever?

In the end, industry is going to put its money where it can make a profit - and while that might include gene therapy for cancer, rare genetic diseases just don't fit the bill. Chattopadhyay pointed to Enzon Pharmaceuticals Inc., which charges $250,000 to $500,000 per year for its ADA-SCID enzyme replacement and still failed to turn a profit in 2008. He also noted that Genzyme Corp. - poster child for treating orphan diseases - made its latest mipomersen deal with an eye toward broader markets.

Which begs the question: If industry isn't going to fund gene therapy for orphan diseases, who will?

Bodine is hopeful that small venture capitalists could find a niche in the space, and he noted that gene therapy gets strong patient advocacy support - although the groups are often too small to generate significant funding.

Chattopadhyay predicted the money will have to come from government, perhaps as part of an NIH special allocation for universities or companies working on orphan diseases.

Trista Morrison can be reached at

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